Combination Therapies for Treating TROP-2-Expressing Cancers

Abstract

Methods are provided for treating, ameliorating, or preventing or delaying the growth, proliferation, recurrence or metastasis of a Trop-2-expressing cancer in a subject by administering to the subject effective amounts of (a) an agent that inhibits the binding between CD47 and SIRPα (e.g., magrolimab); and (b) an anti-Trop-2 antibody drug conjugate (ADC) (e.g., sacituzumab govitecan).

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Application No. 63 / 323,380, filed March 24, 2022, which is incorporated by reference herein in its entirety for all purposes.

[0002] Sequence Listing This application contains a Sequence Listing that has been submitted electronically in XML file format, which is incorporated by reference in its entirety. The XML copy created on January 15, 2023 is named 1432-WO-PCT_SL.xml and is 395,927 bytes in size. [Background technology]

[0003] Triple-negative breast cancer (TNBC) is defined by the absence of immunostaining for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Approximately 15%-20% of all breast cancers are classified as TNBC. In general, compared with other breast cancer subtypes, TNBC typically has more aggressive characteristics, including a faster proliferation rate and a more invasive phenotype. Patients with locally advanced or metastatic TNBC (mTNBC) have a poor prognosis. The standard of care for patients with mTNBC is chemotherapy. Taxane-based chemotherapy regimens are considered the standard of care in the first-line (1L) treatment of patients with mTNBC (Cardoso, et al., Hepatology AASLD Abstracts (2012) 56(4):384A-5A), with single-agent taxanes as the recommended chemotherapy regimen across international guidelines. However, even with these agents, the median overall survival (OS) is approximately 18 months or less (Cardoso, et al., Ann Oncol. (2020) 31(12): 1623-1649; Gradishar, et al., J Natl Compr Canc Netw (2020) 18(4): 452-78).

[0004] Patients with TNBC who have failed approved or tolerated therapies in the first- and second-line settings are in dire need of additional therapeutic approaches. The trophoblast cell surface antigen 2 (Trop-2) antigen is highly expressed in most solid epithelial cancers, including TNBC. Sacituzumab govitecan is a Trop-2-targeted antibody with the topoisomerase I inhibitor camptothecin-derived drug SN-38 as its payload that binds to Trop-2 for targeted delivery of SN-38 directly to tumor cells while minimizing systemic exposure of SN-38 to reduce host toxicity. Results from the ASCENT study evaluating sacituzumab govitecan monotherapy in patients with locally advanced or mTNBC who have relapsed after at least two prior chemotherapy regimens for breast cancer (one of which may be in the neoadjuvant / adjuvant setting if progression occurs within a 12-month period) showed a benefit in terms of PFS versus single-agent chemotherapy. Patients treated with sacituzumab govitecan had a median PFS of 5.6 months versus 1.7 months in single-agent chemotherapy. The study also showed improved overall survival of 12.1 months in the sacituzumab govitecan arm versus 6.7 months in the chemotherapy arm (Bardia, et al., N Engl J Med (2021) 384 (16): 1529-41). The results of this study led to the approval of sacituzumab govitecan in patients with unresectable locally advanced or mTNBC who have received two or more prior systemic therapies, at least one of which was for metastatic disease.

[0005] Cluster of differentiation 47 (CD47) is a molecule that mediates cancer cell evasion of innate immune surveillance. CD47 expression is a well-characterized mechanism by which cancer cells, including cancer stem cells, overcome phagocytosis due to endogenous expression of phagocytic "eat me" signals (Jaiswal, et al., Cell (2009) 138(2): 271-85; Majeti, et al., Cell (2009) 138(2): 286-99). Progression of normal cells to cancer cells involves changes in genes and gene expression that lead to programmed cell death and programmed cell elimination (Chao, et al., Nat Rev Cancer. (2012) 12(1): 58-67). Many of the steps in cancer progression subvert multiple mechanisms of programmed cell death, and expression of CD47, the predominant anti-phagocytic signal, may represent a critical checkpoint (Chao, et al., 2012, supra). Increased CD47 expression was first identified on leukemic stem cells in human acute myeloid leukemia (AML) (Majeti, et al., 2009, supra), and since then, CD47 expression has been found to be increased on the cancer cell surface in a diverse set of human tumor types.

[0006] In mouse xenograft models, CD47-blocking monoclonal antibodies (mAbs) inhibit human xenograft tumor growth and metastasis by enabling phagocytosis and elimination of cancer cells from a variety of hematological malignancies and solid tumors (Chao, et al., Cancer Res (2011) 71(4):1374-84; Chao, et al., Cell (2010) 142:699-713; Chao, et al., Blood (2011) 118(18):4890-901; Edris, et al., Proc Natl Acad Sci USA (2012) 109(17):6656-61; Kim, et al., Proc Natl Acad Sci USA (2012) 109(17):6656-61; Majeti, et al., supra; Willingham, et al., Proc Natl Acad Sci USA (2012) 109(17):6656-61; USA (2012) 109(17):6662-7). Binding of CD47 expressed by cancer cells to its ligand signal regulatory protein alpha (SIRPα) expressed in phagocytes results in inhibition of tumor cell phagocytosis. Thus, blocking the CD47 SIRPα signaling pathway with anti-CD47 antibodies results in phagocytosis and elimination of tumor cells. The selective targeting of tumor cells by anti-CD47 antibodies is due to the presence of phagocytic signals that are primarily expressed in tumor cells and not in their normal cell counterparts (Chao, et al., Sci Transl Med (2010) 2(63):63ra94). Furthermore, anti-CD47 antibodies can induce anti-cancer T cell responses through cross-presentation of tumor antigens by macrophages and antigen-presenting cells after tumor cell phagocytosis (Liu, et al., Nat Med (2015) 21(10): 1209-15, Tseng, et al., Proc Natl Acad Sci USA (2013) 110(27): 11103-8).

[0007] Magrolimab is a humanized anti-CD47 mAb that blocks the interaction of CD47 with its receptors, allowing the phagocytosis of human cancer cells (Liu, et al., PLoS One. (2015) 10(9): e0137345). Although the presence of the immunoglobulin G4 (IgG4) Fc domain is required for its full activity, the activity of magrolimab depends primarily on blocking CD47 binding to SIRPα and not on recruiting fragment crystallizable (Fc)-dependent effector functions. For this reason, magrolimab was engineered with a human IgG4 isotype, which is relatively inefficient at recruiting Fc-dependent effector functions that may enhance toxic effects against normal CD47-expressing cells (Liu, et al., PLoS One. (2015), supra). Preclinical studies using xenograft cancer models provide compelling evidence that magrolimab induces the phagocytosis and elimination of cancer cells from human solid tumors and hematological malignancies. Based on this mechanism of action (MOA) and its potent preclinical activity, magrolimab is being developed as a potential treatment for solid tumors and hematological malignancies. Sacituzumab govitecan, sold under the trade name TRODELVY®, is an antibody-drug conjugate composed of three compounds: a humanized monoclonal antibody, a topoisomerase-I inhibitor, and a linker protein. It binds to Trop-2)-expressing cells and forms an internalization complex that releases SN-38 into the cell. SN-38 binds to the topoisomerase I-DNA complex, causing DNA damage and apoptosis. Sacituzumab govitecan has been approved in several countries, including the United States, Canada, the EU, and Australia, for the treatment of unresectable locally advanced or mTNBC. The approval for TNBC was based on a phase 3, multicenter study of the ASCENT protocol with 468 patients with relapsed / refractory TNBC (Bardia, et al., N Engl J Med (2021) 384 (16): 1529-41). Patients were randomly assigned to receive sacituzumab govitecan (235 patients) or chemotherapy (233 patients). The median age was 54 years, and all patients had been previously treated with a taxane and had no brain metastases. Sacituzumab govitecan was administered at 10 mg / kg on days 1 and 8 every 21 days until progression or unacceptable toxicity. Sacituzumab govitecan demonstrated a longer median PFS (5.6 months vs. 1.7 months) and a longer median overall survival (12.1 months vs. 6.7 months) than the chemotherapy treatment group. The percentage of patients with an objective response was 35% with sacituzumab govitecan and 5% with chemotherapy. [Prior art documents] [Non-patent literature]

[0008] [Non-Patent Document 1] Cardoso, et al., Hepatology AASLD Abstracts(2012)56(4):384A-5A [Non-Patent Document 2] Cardoso,et al.,Ann Oncol.(2020)31(12):1623-1649 [Non-Patent Document 3] Gradishar, et al., J Natl Compr Canc Netw(2020)18(4):452-78

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Summary of the Invention

[0009] In one aspect, a method of treating, ameliorating, reducing, preventing or delaying the growth, proliferation, recurrence or metastasis of a Trop-2 positive or Trop-2 expressing cancer in a mammalian subject in need thereof is provided, comprising co-administering to the subject an effective amount of (a) an anti-Trop-2 antibody-drug conjugate (ADC); and (b) an agent that inhibits binding between CD47 and SIRPα. In some embodiments, the Trop-2 positive or Trop-2 expressing cancer is a solid epithelial cancer. In some embodiments, the cancer is selected from breast cancer (e.g., triple-negative breast cancer), colorectal cancer, lung cancer, gastric cancer, urinary tract cancer, urothelial cancer, bladder cancer, kidney cancer, pancreatic cancer, ovarian cancer, uterine cancer, esophageal cancer and prostate cancer. In some embodiments, the cancer is (i) unresectable, locally advanced, or (ii) metastatic. In some embodiments, the cancer is selected from metastatic non-small cell lung cancer, metastatic small cell lung cancer, metastatic urothelial cancer and metastatic pancreatic cancer. In some embodiments, the cancer is a breast cancer selected from triple negative breast cancer, HR+ / HER2- breast cancer, and HER2+ breast cancer. In some embodiments, the treatment results in a reduction in total tumor burden of at least 15%, at least 20%, at least 30%, or at least 40% as determined using a linear bidimensional method (e.g., RECIST v1.1). In some embodiments, the method includes reducing the size of metastases or eliminating metastases. In some embodiments, the cancer does not recur or the tumor burden does not regrow after cessation of treatment. In some embodiments, the cancer has cell surface expression of CD47. In some embodiments, the agent that inhibits binding between CD47 and SIRPα includes an antibody that binds to CD47. In some embodiments, the antibody that binds CD47 is selected from magrolimab, lemzoparlimab, retaplimab, ligfalimab, AO-176, simlidarlimab (IBI-322), gentulizumab, ZL-1201, IMC-002, SRF-231, CC-90002 (also known as INBRX-103), NI-1701 (also known as TG-1801), and STI-6643.In some embodiments, the agent that inhibits binding between CD47 and SIRPα comprises an antibody that binds to SIRPα. In some embodiments, the antibody that binds to SIRPα is selected from GS-0189 (also known as FSI-189), CC-95251, BI-765063, and APX-700. In some embodiments, the agent that inhibits binding between CD47 and SIRPα comprises a SIRPα-Fc fusion protein. In some embodiments, the SIRPα-Fc fusion protein is selected from ALX-148 (evoluptor), timdarpacept, TTI-621, TTI-622, JMT601 (CPO107), and SL-172154. In some embodiments, the anti-Trop-2 ADC comprises a topoisomerase I inhibitor. In some embodiments, the topoisomerase I inhibitor is selected from irinotecan, topetecan, and SN-38. In some embodiments, the anti-Trop-2 ADC has the structural formula of mAb-CL2A-SN-38), the structure of which is represented by the following: [ka] (e.g., as described in U.S. Pat. No. 7,999,083). In some embodiments, the anti-Trop-2 ADC comprises sacituzumab (hRS7; e.g., as disclosed in WO2003074566, Figures 3 and 4). In some embodiments, the anti-Trop-2 ADC is selected from sacituzumab govitecan, datopotamab deruxtecan (DS-1062), ESG-401, SKB-264, DAC-02, and BAT-8003. In some embodiments, the anti-Trop-2 ADC comprises sacituzumab govitecan. In some embodiments, the agent that inhibits binding between CD47 and SIRPα and the anti-Trop-2 ADC are administered simultaneously or sequentially. In some embodiments, magrolimab is administered at a subtherapeutic dose. In some embodiments, sacituzumab govitecan is administered at a subtherapeutic dose. In some embodiments, magrolimab and sacituzumab govitecan are co-administered at sub-therapeutic doses. In some embodiments, the method further comprises administering a taxane. In some embodiments, the taxane is selected from paclitaxel, nab-paclitaxel (ABRAXANE®), docetaxel, and cabazitaxel. In some embodiments, the method further comprises administering one or more therapeutic antibodies. In some embodiments, the method further comprises co-administering one or more blockers or inhibitors of one or more T cell stimulatory immune checkpoint proteins or receptors. In some embodiments, the one or more immune checkpoint inhibitors comprise a proteinaceous (e.g., antibody) inhibitor of PD-L1 (CD274), PD-1 (PDCD1), or CTLA4. In some embodiments, the one or more immune checkpoint proteins or receptors are selected from CD274 (CD274, PDL1, PD-L1) and programmed cell death 1 (PDCD1, PD1, PD-1).In some embodiments, proteinaceous (e.g., antibody) inhibitors of CTLA4 include ipilimumab, tremelimumab, BMS-986218, AGEN1181, AGEN1884 (zalifrelimab), BMS-986249, MK-1308, REGN-4659, ADU-1604, CS-1002, BCD-145, APL-509, JS-007, BA-3071, ONC-392, AGEN-2041, JHL-1155, K N-044, CG-0161, ATOR-1144, PBI-5D3H5, FPT-155 (CTLA4 / PD-L1 / CD28), PF-06936308 (PD-1 / CTLA4), MGD-019 (PD-1 / C TLA4), KN-046 (PD-1 / CTLA4), MEDI-5752 (CTLA4 / PD-1), XmAb-20717 (PD-1 / CTLA4), and AK-104 (CTLA4 / PD-1).In some embodiments, proteinaceous (e.g., antibody) inhibitors of programmed cell death 1 (PDCD1; NCBI Gene ID: 5133; CD279, PD-1, PD1) include, but are not limited to, zimberelimab (AB122, GLS-010, WBP-3055), pembrolizumab (KEYTRUDA®, MK-3475, SCH900475), nivolumab (OPDIVO®, BMS-936558, MDX-1106), cemiplimab (LIBTAYO®; cemiplimab-rwlc, REGN-2810), pidilizumab (CT-011), AMG-404, MEDI0680 (AMP-514), spa Rutalizumab (PDR001), tislelizumab (BGB-A317), toripalimab (JS-001), genolimuzumab (CBT-501, APL-501, GB226), SHR-1201, camrelizumab (SHR-1210), sintilimab (TYVYT®; IBI-308), dostallimab (TSR-042, WBP-285), lambrolizumab (MK-3475); sasanlimumab (PF-06801591), cetrelimab (JNJ-63723283), serplulimab (HLX-10), retifanlimab (MGA-012), balstilimab (AGEN2034), prorugolimab (BCD 100), budigalimab (ABBV-181), bopratelimab (JTX-4014), AK-103 (HX-008), AK-105, CS 1003, BI-754091, LZM-009, Sym-021, BAT-1306, PD1-PIK, tevotelimab (MGD013;PD-1 / LAG-3 ), RO-7247669(PD-1 / LAG-3), FS-118(LAG-3 / PD-L1), RO-7121661(PD1 / TIM-3), RG7769 (PD-1 / TIM-3), PF-06936308 (PD1 / CTLA4), MGD-019 (PD-1 / CTLA4), KN-046 (PD1 / CTLA4), XmAb-20717 (PD1 / CTLA4), AK-104 (CTLA4 / PD-1), and MEDI-5752 (CTLA4 / PD-1).In some embodiments, proteinaceous (e.g., antibody) inhibitors of the CD274 molecule (NCBI Gene ID: Gene ID:29126; B7-H, B7H1, PD-L1) include atezolizumab (TECENTRIQ®), avelumab (BAVENCIO®; MSB0010718C), embafolimab (ASC22), durvalumab (IMFINZI®; MEDI-4736), BMS-936559 (MDX1105), cosibelimab (CK-301), lodapolimab (LY3300054), garivulimab (BGB A333), embafolimab (KN035), opcolimab (HLX 20), manelimab (BCD 135), CX-072, CBT-502 (TQB2450), MSB-2311, SHR-1316, sugemalimab (CS-1001; WBP3155), A167 (KL-A167, HBM9167), STI-A1015 (IMC-001), FAZ-053, BMS-936559 (MDX1105), INCB086550, GEN-1046 (PD-L1 / 4-1 BB), FPT-155 (CTLA4 / PD-L1 / CD28), M7824 (PD-L1 / TGFβ-EC domain), CA-170 (PD-L1 / VISTA), CDX-527 (CD27 / PD-L1), LY-3415244 (TIM-3 / PDL1), INBRX-105 (4-1BB / PDL1), and GNS-1480 (PD-L1 / EGFR). In some embodiments, the method comprises co-administering an agonist of fms-related receptor tyrosine kinase 3 (FLT3). In some embodiments, the FLT3 agonist is selected from GS-3583 and CDX-301. In some embodiments, the agent that inhibits binding between CD47 and SIRPα and the anti-Trop-2 ADC are administered in a combined synergistic amount. In some embodiments, administration of an agent that inhibits binding between CD47 and SIRPα and an anti-Trop-2 ADC results in a synergistic effect, hi some embodiments, the synergistic effect is an increase in cancer cell death and / or a decrease in cancer cell growth when comparing the effect of the combination to either the agent that inhibits binding between CD47 and SIRPα or the anti-Trop-2 ADC alone.In some embodiments, the synergistic effect is increased phagocytosis of cancer cells by macrophages when comparing the effect of the combination to either the agent that inhibits binding between CD47 and SIRPα or the anti-Trop-2 ADC alone. In some embodiments, the synergistic effect is increased or enhanced tumor burden reduction when comparing the effect of the combination to either the agent that inhibits binding between CD47 and SIRPα or the anti-Trop-2 ADC alone. In some embodiments, the subject is human. In some embodiments, the cancer has progressed after at least one prior anti-cancer therapy. In some embodiments, the subject is treatment naive.

[0010] In another aspect, a method of treating, alleviating, reducing, preventing or delaying the growth, proliferation, recurrence or metastasis of cancer in a subject is provided, comprising administering to the subject an effective amount of (a) magrolimab; and (b) sacituzumab govitecan. In some embodiments, the cancer is a solid epithelial cancer. In some embodiments, the cancer is selected from breast cancer (e.g., triple-negative breast cancer), colorectal cancer, lung cancer, gastric cancer, urinary tract cancer, urothelial cancer, bladder cancer, kidney cancer, pancreatic cancer, ovarian cancer, uterine cancer, esophageal cancer and prostate cancer. In some embodiments, the cancer is (i) unresectable, locally advanced, or (ii) metastatic. In some embodiments, the cancer is selected from metastatic non-small cell lung cancer, metastatic small cell lung cancer, metastatic urothelial cancer and metastatic pancreatic cancer. In some embodiments, the cancer is a breast cancer selected from triple-negative breast cancer, HR+ / HER2- breast cancer, and HER2+ breast cancer. In some embodiments, the treatment results in a reduction in total tumor burden of at least 15%, at least 20%, at least 30%, or at least 40% as determined using a linear bidimensional method (e.g., RECIST v1.1). In some embodiments, the method includes reducing the size of metastases or eliminating metastases. In some embodiments, the cancer does not recur or the tumor burden does not regrow after cessation of treatment. In some embodiments, the cancer has cell surface expression of CD47. In some embodiments, magrolimab and sacituzumab govitecan are administered simultaneously or sequentially. In some embodiments, magrolimab is administered at a subtherapeutic dose. In some embodiments, sacituzumab govitecan is administered at a subtherapeutic dose. In some embodiments, magrolimab and sacituzumab govitecan are co-administered at subtherapeutic doses. In some embodiments, the method further includes administering a taxane. In some embodiments, the taxane is selected from paclitaxel, nab-paclitaxel (ABRAXANE®), docetaxel, and cabazitaxel. In some embodiments, the method further comprises co-administering one or more therapeutic antibodies.In some embodiments, the method further comprises co-administering one or more blockers or inhibitors of one or more T cell stimulatory immune checkpoint proteins or receptors. In some embodiments, the one or more immune checkpoint inhibitors comprise a proteinaceous (e.g., antibody) inhibitor of PD-L1 (CD274), PD-1 (PDCD1), or CTLA4. In some embodiments, the one or more immune checkpoint proteins or receptors are selected from CD274 (CD274, PDL1, PD-L1) and programmed cell death 1 (PDCD1, PD1, PD-1). In some embodiments, proteinaceous (e.g., antibody) inhibitors of CTLA4 include ipilimumab, tremelimumab, BMS-986218, AGEN1181, AGEN1884 (zalifrelimab), BMS-986249, MK-1308, REGN-4659, ADU-1604, CS-1002, BCD-145, APL-509, JS-007, BA-3071, ONC-392, AGEN-2041, JHL-1155, K N-044, CG-0161, ATOR-1144, PBI-5D3H5, FPT-155 (CTLA4 / PD-L1 / CD28), PF-06936308 (PD-1 / CTLA4), MGD-019 (PD-1 / C TLA4), KN-046 (PD-1 / CTLA4), MEDI-5752 (CTLA4 / PD-1), XmAb-20717 (PD-1 / CTLA4), and AK-104 (CTLA4 / PD-1).In some embodiments, proteinaceous (e.g., antibody) inhibitors of programmed cell death 1 (PDCD1; NCBI Gene ID: 5133; CD279, PD-1, PD1) include, but are not limited to, zimberelimab (AB122, GLS-010, WBP-3055), pembrolizumab (KEYTRUDA®, MK-3475, SCH900475), nivolumab (OPDIVO®, BMS-936558, MDX-1106), cemiplimab (LIBTAYO®; cemiplimab-rwlc, REGN-2810), pidilizumab (CT-011), AMG-404, MEDI0680 (AMP-514), spa Rutalizumab (PDR001), tislelizumab (BGB-A317), toripalimab (JS-001), genolimuzumab (CBT-501, APL-501, GB226), SHR-1201, camrelizumab (SHR-1210), sintilimab (TYVYT®; IBI-308), dostallimab (TSR-042, WBP-285), lambrolizumab (MK-3475); sasanlimumab (PF-06801591), cetrelimab (JNJ-63723283), serplulimab (HLX-10), retifanlimab (MGA-012), balstilimab (AGEN2034), prorugolimab (BCD 100), budigalimab (ABBV-181), bopratelimab (JTX-4014), AK-103 (HX-008), AK-105, CS 1003, BI-754091, LZM-009, Sym-021, BAT-1306, PD1-PIK, tevotelimab (MGD013;PD-1 / LAG-3 ), RO-7247669(PD-1 / LAG-3), FS-118(LAG-3 / PD-L1), RO-7121661(PD1 / TIM-3), RG7769 (PD-1 / TIM-3), PF-06936308 (PD1 / CTLA4), MGD-019 (PD-1 / CTLA4), KN-046 (PD1 / CTLA4), XmAb-20717 (PD1 / CTLA4), AK-104 (CTLA4 / PD-1), and MEDI-5752 (CTLA4 / PD-1).In some embodiments, proteinaceous (e.g., antibody) inhibitors of the CD274 molecule (NCBI Gene ID: Gene ID:29126; B7-H, B7H1, PD-L1) are selected from the group consisting of atezolizumab (TECENTRIQ®), avelumab (BAVENCIO®; MSB0010718C), embafolimab (ASC22), durvalumab (IMFINZI®; MEDI-4736), BMS-936559 (MDX1105), cosibelimab (CK-301), lodapolimab (LY3300054), galibrimab (BGB A333), embafolimab (KN035), opcolimab (HLX20), manelimab (BCD135), CX-072, CBT-502 (TQB2450), MSB-2311, SHR-1316, sugemalimab (CS-1001; WBP3155), A167 (KL-A167, HBM9167), STI-A1015 (IMC-001), FAZ-053, BMS-936559 (MDX1105), INCB086 550, GEN-1046 (PD-L1 / 4-1BB), FPT-155 (CTLA4 / PD-L1 / CD28), M7824 (PD-L1 / TGFβ-EC domain), CA-170 (PD-L1 / VISTA), CDX-527 (CD27 / PD-L1), LY-3415244 (TIM-3 / PDL1), INBRX-105 (4-1BB / PDL1), and GNS-1480 (PD-L1 / EGFR). In some embodiments, the method comprises co-administering an agonist of fms-related receptor tyrosine kinase 3 (FLT3). In some embodiments, the agonist of FLT3 is selected from GS-3583 and CDX-301. In some embodiments, magrolimab and sacituzumab govitecan are administered in a combined synergistic amount. In some embodiments, administration of magrolimab and sacituzumab govitecan results in a synergistic effect, hi some embodiments, the synergistic effect is an increase in cancer cell death and / or a decrease in cancer cell growth when comparing the effect of the combination to either magrolimab or sacituzumab govitecan alone.In some embodiments, the synergistic effect is increased phagocytosis of cancer cells by macrophages when comparing the effect of the combination to either magrolimab or sacituzumab govitecan alone. In some embodiments, the synergistic effect is increased or enhanced tumor burden reduction when comparing the effect of the combination to either magrolimab or sacituzumab govitecan alone. In some embodiments, magrolimab is administered initially at a priming dose of less than 10 mg / kg, followed by one or more therapeutic doses of at least 15 mg / kg, e.g., at least 30 mg / kg, 45 mg / kg, 60 mg / kg. In some embodiments, magrolimab is administered initially at a priming dose of less than 5 mg / kg, followed by one or more therapeutic doses of at least 30 mg / kg, e.g., 45 mg / kg, 60 mg / kg. In some embodiments, magrolimab is administered initially at a priming dose of 1 mg / kg, then at one or more therapeutic doses of 30 mg / kg, followed by one or more therapeutic doses of 60 mg / kg. In some embodiments, magrolimab is administered initially at a priming dose of 1 mg / kg, then at one or more therapeutic doses of 20 mg / kg, followed by one or more therapeutic doses of 45 mg / kg. In some embodiments, magrolimab is administered initially at a priming dose of 1 mg / kg, then at one or more therapeutic doses of 15 mg / kg, followed by one or more therapeutic doses of 30 mg / kg. In some embodiments, magrolimab is administered intravenously, subcutaneously, or intratumorally. In some embodiments, magrolimab is administered intravenously, e.g., through an in-line filter, e.g., through an in-line filter having a pore size of 5 μm, e.g., through an in-line filter having a pore size of 1.2 μm, e.g., through an in-line filter having a pore size of 0.45 μm, e.g., through an in-line filter having a pore size of 0.22 μm. In some embodiments, sacituzumab govitecan is administered at one or more doses ranging from 3 mg / kg to 18 mg / kg, e.g., 8 mg / kg to 10 mg / kg.In some embodiments, sacituzumab govitecan is administered at one or more doses of 10 mg / kg. In some embodiments, sacituzumab govitecan is administered intravenously, subcutaneously, or intratumorally. In some embodiments, the subject is a human. In some embodiments, the cancer has progressed after at least one prior anti-cancer therapy. In some embodiments, the subject is treatment naive.

[0011] In another aspect, a method of treating, ameliorating, reducing, preventing or delaying the growth, proliferation, recurrence or metastasis of triple-negative breast cancer (TNBC) in a subject is provided, comprising administering to the subject an effective amount of (a) magrolimab; and (b) sacituzumab govitecan. In some embodiments, the TNBC is (i) unresectable, locally advanced, or (ii) metastatic. In some embodiments, the treatment results in a reduction in total tumor burden of at least 15%, at least 20%, at least 30%, or at least 40%, as determined using a linear bidimensional method (e.g., RECIST v1.1). In some embodiments, the method includes reducing the size of the metastases or eliminating the metastases. In some embodiments, the cancer does not recur or the tumor burden does not regrow after cessation of treatment. In some embodiments, the TNBC has cell surface expression of CD47. In some embodiments, magrolimab and sacituzumab govitecan are administered simultaneously or sequentially. In some embodiments, magrolimab is administered at a sub-therapeutic dose. In some embodiments, sacituzumab govitecan is administered at a subtherapeutic dose. In some embodiments, magrolimab and sacituzumab govitecan are co-administered at subtherapeutic doses. In some embodiments, the method further comprises administering a taxane. In some embodiments, the taxane is selected from paclitaxel, nab-paclitaxel (ABRAXANE®), docetaxel, and cabazitaxel. In some embodiments, the method further comprises administering one or more therapeutic antibodies. In some embodiments, the method further comprises co-administering one or more blockers or inhibitors of one or more T cell stimulatory immune checkpoint proteins or receptors. In some embodiments, the one or more immune checkpoint inhibitors comprise a proteinaceous (e.g., antibody) inhibitor of PD-L1 (CD274), PD-1 (PDCD1), or CTLA4. In some embodiments, the one or more immune checkpoint proteins or receptors are selected from CD274 (CD274, PDL1, PD-L1) and programmed cell death 1 (PDCD1, PD1, PD-1).In some embodiments, proteinaceous (e.g., antibody) inhibitors of CTLA4 include ipilimumab, tremelimumab, BMS-986218, AGEN1181, AGEN1884 (zalifrelimab), BMS-986249, MK-1308, REGN-4659, ADU-1604, CS-1002, BCD-145, APL-509, JS-007, BA-3071, ONC-392, AGEN-2041, JHL-1155, K N-044, CG-0161, ATOR-1144, PBI-5D3H5, FPT-155 (CTLA4 / PD-L1 / CD28), PF-06936308 (PD-1 / CTLA4), MGD-019 (PD-1 / C TLA4), KN-046 (PD-1 / CTLA4), MEDI-5752 (CTLA4 / PD-1), XmAb-20717 (PD-1 / CTLA4), and AK-104 (CTLA4 / PD-1).In some embodiments, proteinaceous (e.g., antibody) inhibitors of programmed cell death 1 (PDCD1; NCBI Gene ID: 5133; CD279, PD-1, PD1) include, but are not limited to, zimberelimab (AB122, GLS-010, WBP-3055), pembrolizumab (KEYTRUDA®, MK-3475, SCH900475), nivolumab (OPDIVO®, BMS-936558, MDX-1106), cemiplimab (LIBTAYO®; cemiplimab-rwlc, REGN-2810), pidilizumab (CT-011), AMG-404, MEDI0680 (AMP-514), spa Rutalizumab (PDR001), tislelizumab (BGB-A317), toripalimab (JS-001), genolimuzumab (CBT-501, APL-501, GB226), SHR-1201, camrelizumab (SHR-1210), sintilimab (TYVYT®; IBI-308), dostallimab (TSR-042, WBP-285), lambrolizumab (MK-3475); sasanlimumab (PF-06801591), cetrelimab (JNJ-63723283), serplulimab (HLX-10), retifanlimab (MGA-012), balstilimab (AGEN2034), prorugolimab (BCD 100), budigalimab (ABBV-181), bopratelimab (JTX-4014), AK-103 (HX-008), AK-105, CS 1003, BI-754091, LZM-009, Sym-021, BAT-1306, PD1-PIK, tevotelimab (MGD013;PD-1 / LAG-3 ), RO-7247669(PD-1 / LAG-3), FS-118(LAG-3 / PD-L1), RO-7121661(PD1 / TIM-3), RG7769 (PD-1 / TIM-3), PF-06936308 (PD1 / CTLA4), MGD-019 (PD-1 / CTLA4), KN-046 (PD1 / CTLA4), XmAb-20717 (PD1 / CTLA4), AK-104 (CTLA4 / PD-1), and MEDI-5752 (CTLA4 / PD-1).In some embodiments, proteinaceous (e.g., antibody) inhibitors of the CD274 molecule (NCBI Gene ID: Gene ID:29126; B7-H, B7H1, PD-L1) are selected from the group consisting of atezolizumab (TECENTRIQ®), avelumab (BAVENCIO®; MSB0010718C), embafolimab (ASC22), durvalumab (IMFINZI®; MEDI-4736), BMS-936559 (MDX1105), cosibelimab (CK-301), lodapolimab (LY3300054), galibrimab (BGB A333), embafolimab (KN035), opcolimab (HLX 20), manelimab (BCD 135), CX-072, CBT-502 (TQB2450), MSB-2311, SHR-1316, sugemalimab (CS-1001; WBP3155), A167 (KL-A167, HBM9167), STI-A1015 (IMC-001), FAZ-053, BMS-936559 (MDX1105), INCB086550, GEN-1046 (PD-L1 / 4-1 BB), FPT-155 (CTLA4 / PD-L1 / CD28), M7824 (PD-L1 / TGFβ-EC domain), CA-170 (PD-L1 / VISTA), CDX-527 (CD27 / PD-L1), LY-3415244 (TIM-3 / PDL1), INBRX-105 (4-1BB / PDL1), and GNS-1480 (PD-L1 / EGFR). In some embodiments, the method comprises co-administering an agonist of fms-related receptor tyrosine kinase 3 (FLT3). In some embodiments, the FLT3 agonist is selected from GS-3583 and CDX-301. In some embodiments, magrolimab and sacituzumab govitecan are administered in a combined synergistic amount. In some embodiments, administration of magrolimab and sacituzumab govitecan results in a synergistic effect, hi some embodiments, the synergistic effect is an increase in cancer cell death and / or a decrease in cancer cell growth when comparing the effect of the combination to either magrolimab or sacituzumab govitecan alone.In some embodiments, the synergistic effect is increased phagocytosis of cancer cells by macrophages when comparing the effect of the combination to either magrolimab or sacituzumab govitecan alone. In some embodiments, the synergistic effect is increased or enhanced tumor burden reduction when comparing the effect of the combination to either magrolimab or sacituzumab govitecan alone. In some embodiments, magrolimab is administered initially at a priming dose of less than 10 mg / kg, followed by one or more therapeutic doses of at least 15 mg / kg, e.g., at least 30 mg / kg, 45 mg / kg, 60 mg / kg. In some embodiments, magrolimab is administered initially at a priming dose of less than 5 mg / kg, followed by one or more therapeutic doses of at least 30 mg / kg, e.g., 45 mg / kg, 60 mg / kg. In some embodiments, magrolimab is administered initially at a priming dose of 1 mg / kg, then at one or more therapeutic doses of 30 mg / kg, followed by one or more therapeutic doses of 60 mg / kg. In some embodiments, magrolimab is administered initially at a priming dose of 1 mg / kg, then at one or more therapeutic doses of 20 mg / kg, followed by one or more therapeutic doses of 45 mg / kg. In some embodiments, magrolimab is administered initially at a priming dose of 1 mg / kg, then at one or more therapeutic doses of 15 mg / kg, followed by one or more therapeutic doses of 30 mg / kg. In some embodiments, magrolimab is administered intravenously, subcutaneously, or intratumorally. In some embodiments, magrolimab is administered intravenously, e.g., through an in-line filter, e.g., through an in-line filter having a pore size of 5 μm, e.g., through an in-line filter having a pore size of 1.2 μm, e.g., through an in-line filter having a pore size of 0.45 μm, e.g., through an in-line filter having a pore size of 0.22 μm. In some embodiments, sacituzumab govitecan is administered at one or more doses ranging from 3 mg / kg to 18 mg / kg, e.g., 8 mg / kg to 10 mg / kg.In some embodiments, sacituzumab govitecan is administered at one or more doses of 10 mg / kg. In some embodiments, sacituzumab govitecan is administered intravenously, subcutaneously, or intratumorally. In some embodiments, magrolimab and sacituzumab govitecan are administered in a first 21 day cycle, a second 21 day cycle, and a third 21 day cycle, wherein: (a) in the first 21 day cycle, magrolimab is administered at a dose of 1 mg / kg on day 1 and at a dose of 30 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 1 mg / kg on days 1 or 2 and 8 (i.e., on days 1 and 8, or on days 2 and 8). (b) in a second 21-day cycle, magrolimab is administered at a dose of 30 mg / kg on days 1, 8, and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8; and (c) in a third 21-day cycle, magrolimab is administered at a dose of 60 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8. In some embodiments, magrolimab and sacituzumab govitecan are administered in a first 21 day cycle, a second 21 day cycle, and a third 21 day cycle, where (a) in the first 21 day cycle, magrolimab is administered at a dose of 1 mg / kg on day 1 and at a dose of 20 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 1 mg / kg on days 1 or 2 and 8 (i.e., on days 1 and 8, or on days 2 and 8). (b) in a second 21 day cycle, magrolimab is administered at a dose of 20 mg / kg on days 1, 8, and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8; and (c) in a third 21 day cycle, magrolimab is administered at a dose of 45 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8. In some embodiments, magrolimab and sacituzumab govitecan are administered in the first 21 day cycle, the second 21 day cycle and the third 21 day cycle. and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 or 2 and 8 (i.e., on days 1 and 8, or on days 2 and 8); (b) in a second 21 day cycle, magrolimab is administered at a dose of 15 mg / kg on days 1, 8, and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8; and (c) in a third 21 day cycle, magrolimab is administered at a dose of 30 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8. In some embodiments, the subject is a human. In some embodiments, the TNBC has progressed after at least one prior anti-cancer therapy. In some embodiments, the subject is treatment naive.

[0012] In another method, a method of treating, alleviating, reducing, preventing or delaying the growth, proliferation, recurrence or metastasis of non-small cell lung cancer (NSCLC) in a subject is provided, comprising administering to the subject an effective amount of (a) magrolimab; and (b) sacituzumab govitecan. In some embodiments, the NSCLC is (i) unresectable, locally advanced, or (ii) metastatic. In some embodiments, the cancer is unresectable, locally advanced, and the subject is treatment naive. In some embodiments, the treatment results in a reduction in total tumor burden of at least 15%, at least 20%, at least 30%, or at least 40%, as determined using a linear bidimensional method (e.g., RECIST v1.1). In some embodiments, the method includes reducing the size of the metastases or eliminating the metastases. In some embodiments, the cancer does not recur or the tumor burden does not regrow after cessation of treatment. In some embodiments, the NSCLC has cell surface expression of CD47. In some embodiments, magrolimab and sacituzumab govitecan are administered simultaneously or sequentially. In some embodiments, magrolimab is administered at a subtherapeutic dose. In some embodiments, sacituzumab govitecan is administered at a subtherapeutic dose. In some embodiments, magrolimab and sacituzumab govitecan are co-administered at subtherapeutic doses. In some embodiments, the method further comprises administering a taxane. In some embodiments, the taxane is selected from paclitaxel, nab-paclitaxel (ABRAXANE®), docetaxel, and cabazitaxel. In some embodiments, the method further comprises administering one or more therapeutic antibodies. In some embodiments, the method further comprises co-administering one or more blockers or inhibitors of one or more T cell stimulatory immune checkpoint proteins or receptors. In some embodiments, the one or more immune checkpoint inhibitors comprise a proteinaceous (e.g., antibody) inhibitor of PD-L1 (CD274), PD-1 (PDCD1), or CTLA4.In some embodiments, the one or more immune checkpoint proteins or receptors are selected from CD274 (CD274, PDL1, PD-L1) and programmed cell death 1 (PDCD1, PD1, PD-1). In some embodiments, proteinaceous (e.g., antibody) inhibitors of CTLA4 are selected from ipilimumab, tremelimumab, BMS-986218, AGEN1181, AGEN1884 (zalifrelimab), BMS-986249, MK-1308, REGN-4659, ADU-1604, CS-1002, BCD-145, APL-509, JS-007, BA-3071, ONC-392, AGEN-2041, JHL-1155, K N-044, CG-0161, ATOR-1144, PBI-5D3H5, FPT-155 (CTLA4 / PD-L1 / CD28), PF-06936308 (PD-1 / CTLA4), MGD-019 (PD-1 / C TLA4), KN-046 (PD-1 / CTLA4), MEDI-5752 (CTLA4 / PD-1), XmAb-20717 (PD-1 / CTLA4), and AK-104 (CTLA4 / PD-1).In some embodiments, proteinaceous (e.g., antibody) inhibitors of programmed cell death 1 (PDCD1; NCBI Gene ID: 5133; CD279, PD-1, PD1) include, but are not limited to, zimberelimab (AB122, GLS-010, WBP-3055), pembrolizumab (KEYTRUDA®, MK-3475, SCH900475), nivolumab (OPDIVO®, BMS-936558, MDX-1106), cemiplimab (LIBTAYO®; cemiplimab-rwlc, REGN-2810), pidilizumab (CT-011), AMG-404, MEDI0680 (AMP-514), spa Rutalizumab (PDR001), tislelizumab (BGB-A317), toripalimab (JS-001), genolimuzumab (CBT-501, APL-501, GB226), SHR-1201, camrelizumab (SHR-1210), sintilimab (TYVYT®; IBI-308), dostallimab (TSR-042, WBP-285), lambrolizumab (MK-3475); sasanlimumab (PF-06801591), cetrelimab (JNJ-63723283), serplulimab (HLX-10), retifanlimab (MGA-012), balstilimab (AGEN2034), prorugolimab (BCD 100), budigalimab (ABBV-181), bopratelimab (JTX-4014), AK-103 (HX-008), AK-105, CS-1003, BI-754091, LZM-009, Sym-021, BAT-1306, PD1-PIK, tebotelimab (MGD013; PD-1 / LAG-3), RO-7247669 (PD-1 / LAG-3), FS-118 (LAG-3 / PD-L1 ), RO-7121661(PD-1 / TIM-3), RG7769(PD-1 / TIM-3), PF-06936308(PD-1 / CTLA4), MGD-019(PD-1 / CTLA4), KN -046 (PD-1 / CTLA4), XmAb-20717 (PD-1 / CTLA4), AK-104 (CTLA4 / PD-1), and MEDI-5752 (CTLA4 / PD-1).In some embodiments, proteinaceous (e.g., antibody) inhibitors of the CD274 molecule (NCBI Gene ID: Gene ID:29126; B7-H, B7H1, PD-L1) are selected from the group consisting of atezolizumab (TECENTRIQ®), avelumab (BAVENCIO®; MSB0010718C), embafolimab (ASC22), durvalumab (IMFINZI®; MEDI-4736), BMS-936559 (MDX1105), cosibelimab (CK-301), lodapolimab (LY3300054), galibrimab (BGB A333), embafolimab (KN035), opcolimab (HLX20), manelimab (BCD135), CX-072, CBT-502 (TQB2450), MSB-2311, SHR-1316, sugemalimab (CS-1001; WBP3155), A167 (KL-A167, HBM9167), STI-A1015 (IMC-001), FAZ-053, BMS-936559 (MDX1105), INCB086 550, GEN-1046 (PD-L1 / 4-1BB), FPT-155 (CTLA4 / PD-L1 / CD28), M7824 (PD-L1 / TGFβ-EC domain), CA-170 (PD-L1 / VISTA), CDX-527 (CD27 / PD-L1), LY-3415244 (TIM-3 / PDL1), INBRX-105 (4-1BB / PDL1), and GNS-1480 (PD-L1 / EGFR). In some embodiments, the method further comprises co-administering an agonist of fms-related receptor tyrosine kinase 3 (FLT3). In some embodiments, the agonist of FLT3 is selected from GS-3583 and CDX-301. In some embodiments, magrolimab and sacituzumab govitecan are administered in a combined synergistic amount. In some embodiments, administration of magrolimab and sacituzumab govitecan results in a synergistic effect, hi some embodiments, the synergistic effect is an increase in cancer cell death and / or a decrease in cancer cell growth when comparing the effect of the combination to either magrolimab or sacituzumab govitecan alone.In some embodiments, the synergistic effect is increased phagocytosis of cancer cells by macrophages when comparing the effect of the combination to either magrolimab or sacituzumab govitecan alone. In some embodiments, the synergistic effect is increased or enhanced tumor burden reduction when comparing the effect of the combination to either magrolimab or sacituzumab govitecan alone. In some embodiments, magrolimab is administered initially at a priming dose of less than 10 mg / kg, followed by one or more therapeutic doses of at least 15 mg / kg, e.g., at least 30 mg / kg, 45 mg / kg, 60 mg / kg. In some embodiments, magrolimab is administered initially at a priming dose of less than 5 mg / kg, followed by one or more therapeutic doses of at least 30 mg / kg, e.g., 45 mg / kg, 60 mg / kg. In some embodiments, magrolimab is administered initially at a priming dose of 1 mg / kg, then at one or more therapeutic doses of 30 mg / kg, followed by one or more therapeutic doses of 60 mg / kg. In some embodiments, magrolimab is administered initially at a priming dose of 1 mg / kg, then at one or more therapeutic doses of 20 mg / kg, followed by one or more therapeutic doses of 45 mg / kg. In some embodiments, magrolimab is administered initially at a priming dose of 1 mg / kg, then at one or more therapeutic doses of 15 mg / kg, followed by one or more therapeutic doses of 30 mg / kg. In some embodiments, magrolimab is administered intravenously, subcutaneously, or intratumorally. In some embodiments, magrolimab is administered intravenously, e.g., through an in-line filter, e.g., through an in-line filter having a pore size of 5 μm, e.g., through an in-line filter having a pore size of 1.2 μm, e.g., through an in-line filter having a pore size of 0.45 μm, e.g., through an in-line filter having a pore size of 0.22 μm. In some embodiments, sacituzumab govitecan is administered at one or more doses ranging from 3 mg / kg to 18 mg / kg, e.g., 8 mg / kg to 10 mg / kg.In some embodiments, sacituzumab govitecan is administered at one or more doses of 10 mg / kg. In some embodiments, sacituzumab govitecan is administered intravenously, subcutaneously, or intratumorally. In some embodiments, magrolimab and sacituzumab govitecan are administered in a first 21 day cycle, a second 21 day cycle, and a third 21 day cycle, wherein: (a) in the first 21 day cycle, magrolimab is administered at a dose of 1 mg / kg on day 1 and at a dose of 30 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 1 mg / kg on days 1 or 2 and 8 (i.e., on days 1 and 8, or on days 2 and 8). (b) in a second 21-day cycle, magrolimab is administered at a dose of 30 mg / kg on days 1, 8, and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8; and (c) in a third 21-day cycle, magrolimab is administered at a dose of 60 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8. In some embodiments, magrolimab and sacituzumab govitecan are administered in a first 21 day cycle, a second 21 day cycle, and a third 21 day cycle, where (a) in the first 21 day cycle, magrolimab is administered at a dose of 1 mg / kg on day 1 and at a dose of 20 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 1 mg / kg on days 1 or 2 and 8 (i.e., on days 1 and 8, or on days 2 and 8). In some embodiments, (b) in a second 21 day cycle, magrolimab is administered at a dose of 20 mg / kg on days 1, 8, and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8; and (c) in a third 21 day cycle, magrolimab is administered at a dose of 45 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8. Magrolimab and sacituzumab govitecan are administered in a first 21-day cycle, a second 21-day cycle, and a third 21-day cycle, where: (a) in the first 21-day cycle, magrolimab is administered at a dose of 1 mg / kg on day 1 and at a dose of 15 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1, or 2, and 8 (i.e., on days 1 and 8, or on days 2 and 8). (b) in a second 21 day cycle, magrolimab is administered at a dose of 15 mg / kg on days 1, 8, and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8; and (c) in a third 21 day cycle, magrolimab is administered at a dose of 30 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8. In some embodiments, the subject is a human. In some embodiments, the NSCLC has progressed after at least one prior anti-cancer therapy. In some embodiments, the subject is treatment naive.

[0013] In another aspect, a kit is provided that includes one or more unit doses of (a) an agent that inhibits binding between CD47 and SIRPα; and (b) an anti-Trop-2 antibody-drug conjugate (ADC). In some embodiments, the agent that inhibits binding between CD47 and SIRPα and the anti-Trop-2 ADC are in separate containers. In some embodiments, the separate containers are selected from a vial, an ampoule, and a pre-filled syringe. In some embodiments, the agent that inhibits binding between CD47 and SIRPα comprises an antibody that binds to CD47. In some embodiments, the antibody that binds to CD47 is selected from magrolimab, lemzoparlimab, retaplimab, ligufalimab, AO-176, simlidarlimab (IBI-322), gentulizumab, ZL-1201, IMC-002, SRF-231, CC-90002 (also known as INBRX-103), NI-1701 (also known as TG-1801), and STI-6643. In some embodiments, the agent that inhibits binding between CD47 and SIRPα comprises an antibody that binds to SIRPα. In some embodiments, the antibody that binds to SIRPα is selected from GS-0189 (also known as FSI-189), CC-95251, BI-765063, and APX-700. In some embodiments, the agent that inhibits binding between CD47 and SIRPα comprises a SIRPα-Fc fusion protein. In some embodiments, the SIRPα-Fc fusion protein is selected from ALX-148, TTI-621, TTI-622, JMT601 (CPO107), and SL-172154. In some embodiments, the anti-Trop-2 ADC comprises a topoisomerase I inhibitor. In some embodiments, the topoisomerase I inhibitor is selected from irinotecan, topetecan, and SN-38. In some embodiments, the anti-Trop-2 ADC has the structural formula of mAb-CL2A-SN-38, the structure of which is represented by the following: [ka] (e.g., as described in U.S. Pat. No. 7,999,083). In some embodiments, the anti-Trop-2 ADC comprises sacituzumab (hRS7; e.g., as described in WO2003074566, Figures 3 and 4). In some embodiments, the anti-Trop-2 ADC is selected from sacituzumab govitecan, datopotamab deruxtecan (DS-1062), ESG-401, SKB-264, DAC-02, and BAT-8003. In some embodiments, the anti-Trop-2 ADC comprises sacituzumab govitecan. In some embodiments, the kit further comprises one or more unit doses of a taxane. In some embodiments, the taxane is selected from paclitaxel, nab-paclitaxel (ABRAXANE®), docetaxel, and cabazitaxel. In some embodiments, the kit further comprises one or more therapeutic antibodies. In some embodiments, the kit further comprises one or more blockers or inhibitors of one or more T cell inhibitory immune checkpoint proteins or receptors. In some embodiments, the kit further comprises a proteinaceous (e.g., antibody) inhibitor of PD-L1 (CD274), PD-1 (PDCD1), or CTLA4. In some embodiments, the kit further comprises a proteinaceous (e.g., antibody) inhibitor of PD-L1 (CD274) or PD-1 (PDCD1). In some embodiments, proteinaceous (e.g., antibody) inhibitors of CTLA4 include ipilimumab, tremelimumab, BMS-986218, AGEN1181, AGEN1884 (zalifrelimab), BMS-986249, MK-1308, REGN-4659, ADU-1604, CS-1002, BCD-145, APL-509, JS-007, BA-3071, ONC-392, AGEN2041, JHL-1155, KN -044, CG-0161, ATOR-1144, PBI-5D3H5, FPT-155 (CTLA4 / PD-L1 / CD28), PF-06936308 (PD-1 / CTLA4), MGD-019 (PD-1 / C TLA4), KN-046 (PD-1 / CTLA4), MEDI-5752 (CTLA4 / PD-1), XmAb-20717 (PD-1 / CTLA4), and AK-104 (CTLA4 / PD-1).In some embodiments, proteinaceous (e.g., antibody) inhibitors of programmed cell death 1 (PDCD1; NCBI Gene ID: 5133; CD279, PD-1, PD1) include, but are not limited to, zimberelimab (AB122, GLS-010, WBP-3055), pembrolizumab (KEYTRUDA®, MK-3475, SCH900475), nivolumab (OPDIVO®, BMS-936558, MDX-1106), cemiplimab (LIBTAYO®; cemiplimab-rwlc, REGN-2810), pidilizumab (CT-011), AMG-404, MEDI0680 (AMP-514), spa Rutalizumab (PDR001), tislelizumab (BGB-A317), toripalimab (JS-001), genolimuzumab (CBT-501, APL-501, GB226), SHR-1201, camrelizumab (SHR-1210), sintilimab (TYVYT®; IBI-308), dostallimab (TSR-042, WBP-285), lambrolizumab (MK-3475); sasanlimumab (PF-06801591), cetrelimab (JNJ-63723283), serplulimab (HLX-10), retifanlimab (MGA-012), balstilimab (AGEN2034), prorugolimab (BCD 100), budigalimab (ABBV-181), bopratelimab (JTX-4014), AK-103 (HX-008), AK-105, CS 1003, BI-754091, LZM-009, Sym-021, BAT-1306, PD1-PIK, tevotelimab (MGD013;PD-1 / LAG-3 ), RO-7247669(PD-1 / LAG-3), FS-118(LAG-3 / PD-L1), RO-7121661(PD1 / TIM-3), RG7769 (PD-1 / TIM-3), PF-06936308 (PD1 / CTLA4), MGD-019 (PD-1 / CTLA4), KN-046 (PD1 / CTLA4), XmAb-20717 (PD1 / CTLA4), AK-104 (CTLA4 / PD-1), and MEDI-5752 (CTLA4 / PD-1).In some embodiments, proteinaceous (e.g., antibody) inhibitors of the CD274 molecule (NCBI Gene ID: Gene ID:29126; B7-H, B7H1, PD-L1) are selected from the group consisting of atezolizumab (TECENTRIQ®), avelumab (BAVENCIO®; MSB0010718C), embafolimab (ASC22), durvalumab (IMFINZI®; MEDI-4736), BMS-936559 (MDX1105), cosibelimab (CK-301), lodapolimab (LY3300054), galibrimab (BGB A333), embafolimab (KN035), opcolimab (HLX20), manelimab (BCD135), CX-072, CBT-502 (TQB2450), MSB-2311, SHR-1316, sugemalimab (CS-1001; WBP3155), A167 (KL-A167, HBM9167), STI-A1015 (IMC-001), FAZ-053, BMS-936559 (MDX1105), INCB086 550, GEN-1046 (PD-L1 / 4-1BB), FPT-155 (CTLA4 / PD-L1 / CD28), M7824 (PD-L1 / TGFβ-EC domain), CA-170 (PD-L1 / VISTA), CDX-527 (CD27 / PD-L1), LY-3415244 (TIM-3 / PDL1), INBRX-105 (4-1BB / PDL1), and GNS-1480 (PD-L1 / EGFR). In some embodiments, the kit comprises an agonist of fms-related receptor tyrosine kinase 3 (FLT3). In some embodiments, the agonist of FLT3 is selected from GS-3583 and CDX-301. [Brief description of the drawings]

[0014] [Figure 1] 1 shows a schematic diagram of the study described herein. mTNBC = metastatic triple-negative breast cancer; N = number of patients; R = ratio; RP2D = recommended phase 2 dose.

[0015] [Diagram 2]Figure 1 shows the efficacy of magrolimab, sacituzumab govitecan (TRODELVY®), or their combination to inhibit tumor growth in an orthotopic MDA-MB-468 xenograft model. hIgG4 and hIgG1-ADC Iso were used to control magrolimab and sacituzumab govitecan, respectively. Groups and dosing schemes are listed in Table 4. Dosing was stopped for all treatment groups after 3 weeks while tumor growth continued to be monitored.

[0016] [Figure 3A] Tumor growth data for individual mice are shown plotted for each dose group. Isotype control (Figure 3A), ADC-Iso control (Figure 3B), and sacituzumab govitecan alone (Figure 3C) tumors grew until the mice were euthanized. Treatment with magrolimab alone or magrolimab plus ADC-Iso control (Figures 3D-3E, respectively) initiated tumor regression at approximately day 5, but tumors regrew upon discontinuation of the drugs. Administration of the combination of magrolimab and sacituzumab govitecan induced tumor regression, with mice remaining tumor-free for more than 2 months after cessation of active agents (Figure 3F). [Figure 3B] Tumor growth data for individual mice are shown plotted for each dose group. Isotype control (Figure 3A), ADC-Iso control (Figure 3B), and sacituzumab govitecan alone (Figure 3C) tumors grew until the mice were euthanized. Treatment with magrolimab alone or magrolimab plus ADC-Iso control (Figures 3D-3E, respectively) initiated tumor regression at approximately day 5, but tumors regrew upon discontinuation of the drugs. Administration of the combination of magrolimab and sacituzumab govitecan induced tumor regression, with mice remaining tumor-free for more than 2 months after cessation of active agents (Figure 3F). [Figure 3C]Tumor growth data for individual mice are shown plotted for each dose group. Isotype control (Figure 3A), ADC-Iso control (Figure 3B), and sacituzumab govitecan alone (Figure 3C) tumors grew until the mice were euthanized. Treatment with magrolimab alone or magrolimab plus ADC-Iso control (Figures 3D-3E, respectively) initiated tumor regression at approximately day 5, but tumors regrew upon discontinuation of the drugs. Administration of the combination of magrolimab and sacituzumab govitecan induced tumor regression, with mice remaining tumor-free for more than 2 months after cessation of active agents (Figure 3F). [Figure 3D] Tumor growth data for individual mice are shown plotted for each dose group. Isotype control (Figure 3A), ADC-Iso control (Figure 3B), and sacituzumab govitecan alone (Figure 3C) tumors grew until the mice were euthanized. Treatment with magrolimab alone or magrolimab plus ADC-Iso control (Figures 3D-3E, respectively) initiated tumor regression at approximately day 5, but tumors regrew upon discontinuation of the drugs. Administration of the combination of magrolimab and sacituzumab govitecan induced tumor regression, with mice remaining tumor-free for more than 2 months after cessation of active agents (Figure 3F). [Figure 3E] Tumor growth data for individual mice are shown plotted for each dose group. Isotype control (Figure 3A), ADC-Iso control (Figure 3B), and sacituzumab govitecan alone (Figure 3C) tumors grew until the mice were euthanized. Treatment with magrolimab alone or magrolimab plus ADC-Iso control (Figures 3D-3E, respectively) initiated tumor regression at approximately day 5, but tumors regrew upon discontinuation of the drugs. Administration of the combination of magrolimab and sacituzumab govitecan induced tumor regression, with mice remaining tumor-free for more than 2 months after cessation of active agents (Figure 3F). [Figure 3F]Tumor growth data for individual mice are shown plotted for each dose group. Isotype control (Figure 3A), ADC-Iso control (Figure 3B), and sacituzumab govitecan alone (Figure 3C) tumors grew until the mice were euthanized. Treatment with magrolimab alone or magrolimab plus ADC-Iso control (Figures 3D-3E, respectively) initiated tumor regression at approximately day 5, but tumors regrew upon discontinuation of the drugs. Administration of the combination of magrolimab and sacituzumab govitecan induced tumor regression, with mice remaining tumor-free for more than 2 months after cessation of active agents (Figure 3F).

[0017] [Figure 4] The percent change in body weight for all groups over the dosing period is shown. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0018] 1. Introduction Methods are provided for treating, ameliorating, or preventing or delaying the growth, proliferation, recurrence or metastasis of a Trop-2-expressing cancer in a subject by administering to the subject an effective amount of (a) an agent that inhibits the binding between CD47 and SIRPα (e.g., magrolimab); and (b) an anti-Trop-2 antibody drug conjugate (ADC) (e.g., sacituzumab govitecan). Surprisingly, as demonstrated herein, the combined administration of an agent that inhibits the binding between CD47 and SIRPα (e.g., magrolimab) and an anti-Trop-2 ADC (e.g., sacituzumab govitecan) results in synergistic (i.e., greater than additive) inhibition of phagocytosis of Trop-2-expressing cancer cells and tumor growth. Exemplary Trop-2 expressing cancers include most solid epithelial cancers, including, but not limited to, breast cancer (e.g., triple-negative breast cancer), colorectal cancer, lung cancer, gastric cancer, urinary tract cancer, bladder cancer, kidney cancer, pancreatic cancer, ovarian cancer, uterine cancer, esophageal cancer, and prostate cancer.

[0019] Principle of combination therapy targeting CD47 and Trop-2 simultaneously Overexpression of CD47 has been reported in TNBC and is a poor prognostic factor for disease-free survival (Yuan, et al., Oncol Lett (2019) 18 (3): 3249-3255). Furthermore, there are data suggesting that CD47 is upregulated in chemotherapy-treated TNBC cells, indicating that CD47 is an ideal target for treating drug-resistant or chemotherapy-treated TNBC (Si, et al., Vaccines (Basel) (2021) 9 (8): 882). Although sacituzumab govitecan has demonstrated a significant increase in progression-free survival (PFS) in heavily pretreated patients with TNBC when compared with standard of care therapy, there is still room for further improvement for patients who have failed initial treatment for advanced TNBC. Sacituzumab govitecan was developed to treat cancer by conjugating SN-38 to Trop-2 for targeted delivery directly to tumor cells while minimizing systemic exposure of SN-38 to reduce host toxicity. Trop-2 antigen is highly expressed in most solid epithelial cancers, including TNBC. Sacituzumab govitecan causes DNA damage and apoptosis, which may function as a second proapoptotic signal in tumor cells exposed to magrolimab. The addition of magrolimab to sacituzumab govitecan can have an additive anti-major effect without a significant increase in toxicity due to the non-overlapping safety profile due to the expression of CD47 and Trop-2 on TNBC tumor cells.

[0020] Principles for dose selection of magrolimab The rationale for the magrolimab dose proposed in this study is derived from safety, efficacy, and PK / pharmacodynamic (PD) data and modeling and simulation analyses based on data from all ongoing and completed clinical studies with magrolimab in patients with solid tumors, non-Hodgkin's lymphoma (NHL), and acute myeloid leukemia (AML) / myelodysplastic syndromes (MDS). In addition, non-clinical studies have demonstrated activity against both human solid tumors (e.g., breast, ovarian, pancreatic, colon, leiomyosarcoma, bladder, prostate, etc.) and hematological malignancies (acute myeloid leukemia (AML), acute lymphoblastic leukemia, non-Hodgkin's lymphoma (NHL), myeloma, myelodysplastic syndromes (MDS), among others).

[0021] In a first-in-human study of magrolimab in patients with solid tumors and lymphomas, after an initial priming dose of 1 mg / kg on day 1, magrolimab was tested as monotherapy at weekly doses up to 45 mg / kg. The use of an initial priming dose of 1 mg / kg was incorporated into the dosing regimen to mitigate on-target anemia induced by CD47 blockade. The initial priming dose results in the clearance of senescent RBCs that are sensitive to CD47 blockade and induces reticulocytosis of young RBCs that are unaffected by CD47 blockade (Chen, et al., Blood (ASH Annual Meeting Abstracts) (2018) 132 (Suppl 1): 2327). Utilizing a priming dose results in an initial, transient, mild anemia that generally normalizes to baseline over a few weeks, even in the presence of repeated therapeutic doses of magrolimab (Advani, et al., N Engl J Med (2018) 379(18):1711-21; Liu, et al., PLoS One. (2015) 10(9):e0137345; Sikic, et al., J Clin Oncol (2019) 37(12):946-53). Based on PK-PD modeling, a maintenance dose of 30 mg / kg every 2 weeks is expected to result in greater than 90% occupancy of CD47 receptors in peripheral blood and tumor tissue, and thus is expected to provide maximum efficacy while maintaining adequate safety. In solid tumors where combination therapy is given according to 3-week cycles, dosing of magrolimab every 3 weeks optimizes patient and caregiver convenience. Magrolimab 60 mg / kg every 3 weeks is predicted to result in similar trough concentrations and receptor occupancy (RO) as the 30 mg / kg dose every 2 weeks, which has been used in Phase 3 trials in AML and MDS. Updated pharmacokinetic (PK) modeling from study 5F9005 (NCT03248479) showed that the 45 mg / kg every 3 weeks dose of magrolimab was suboptimal in maintaining trough concentrations compared with 30 mg / kg every 2 weeks and 60 mg / kg every 3 weeks.Maintaining adequate trough concentrations may be necessary for optimal efficacy, given that some patients may experience dose delays due to toxicity. Furthermore, PK / pharmacodynamic (PD) modeling also indicates that RO is maintained at maximal levels (>90%) in peripheral blood and tumor tissues at these extended interval dosing regimens. The proposed dosing regimen of magrolimab in this study is expected to have an acceptable safety profile based on overall safety data in multiple tumor populations, both as monotherapy and in combination with other tumor-targeted antibodies and chemotherapeutic agents.

[0022] Description of Sacituzumab govitecan Trophoblast cell surface antigen 2 (Trop-2) antigen (NCBI gene ID: 4070; aka tumor-associated calcium signaling factor 2 (TACSTD2)) is highly expressed on most solid epithelial cancers, including TNBC. Sacituzumab govitecan is a Trop-2-targeting antibody with the topoisomerase I inhibitor camptothecin-derived drug SN-38 as its payload that binds to Trop-2 for targeted delivery of SN-38 directly to tumor cells while minimizing systemic exposure of SN-38 to reduce host toxicity. Results from the ASCENT study evaluating sacituzumab govitecan monotherapy in patients with locally advanced or mTNBC who have relapsed after at least two prior chemotherapy regimens for breast cancer (one of which may be in the neoadjuvant / adjuvant setting if progression occurs within a 12-month period) showed benefit in terms of PFS versus single-agent chemotherapy. Patients treated with sacituzumab govitecan had a median PFS of 5.6 months versus 1.7 months in single-agent chemotherapy. The study also showed improved overall survival of 12.1 months in the sacituzumab govitecan arm versus 6.7 months in the chemotherapy arm (Bardia, et al., N Engl J Med (2021) 384 (16): 1529-41). The results of this study led to the approval of sacituzumab govitecan in patients with unresectable locally advanced or mTNBC who have received two or more prior systemic therapies, at least one of which was for metastatic disease.

[0023] 2. Agents that inhibit the binding between CD47 and SIRPα a. An antibody or antigen-binding fragment thereof that binds to CD47 In various embodiments, the agent that inhibits binding between CD47 and SIRPα is an antibody or antigen-binding fragment thereof that binds to CD47 (also known as IAP, MER6, OA3; NCBI Gene ID: 961; UniProt Q08722). In various embodiments, the antibody that binds to CD47 has an Fc that has effector function. In various embodiments, the antibody that binds to CD47 is an IgG4 or IgG1. Examples of useful anti-CD47 antibodies include, but are not limited to, magrolimab, lemzoparlimab, retaplimab, ligufalimab (AK117), AO-176, simlidarlimab (IBI-322), gentulizumab, ZL-1201, IMC-002, SRF-231, CC-90002 (also known as INBRX-103), NI-1701 (also known as TG-1801), STI-6643 (Vx-1004), CNTO-7108, RCT-1938, RRx-001, DSP-107, VT-1021, and SGN-CD47M.

[0024] In various embodiments, the antibody targeting CD47 is a bispecific antibody. Examples of bispecific antibodies targeting CD47 include simlidarlimab (IBI-322) (CD47 / PD-L1), IMM-0306 (CD47 / CD20), TJ-L1C4 (CD47 / PD-L1), HX-009 (CD47 / PD-1), PMC-122 (CD47 / PD-L1), PT-217, (CD47 / DLL3), IMM-26011 (CD47 / FLT3), IMM-0207 (CD47 / VEGF), IMM-2902 (CD47 / HER2), BH29xx (CD47 / PD-L1), IMM-03 (CD47 / CD20), IMM-2502 (CD47 / PD-L1), HMBD-004B (CD47 / BCMA), HMBD-004A (CD47 / CD33). Examples of anti-CD47 antibodies include, but are not limited to, IBI-188, TJC-4, SHR-1603, HLX-24, LQ-001, IMC-002, ZL-1201, IMM-01, B6H12, GenSci-059, TAY-018, PT-240, 1F8-GMCSF, SY-102, and KD-015.

[0025] In various embodiments, antibodies targeting CD47 comprise VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences (according to Kabat): SEQ ID NOs: 1, 2, 3, 4, 5 and 6, SEQ ID NOs: 7, 8, 9, 10, 11 and 12, SEQ ID NOs: 13, 14, 15, 16, 17, and 18, SEQ ID NOs: 19, 20, 21, 22, 23 and 24, SEQ ID NOs: 210, 211, 212, 213, 214 and 215, SEQ ID NOs: 216, 217, 218, 219, 220 and 221 SEQ ID NOs: 299, 20, 21, 22, 23 and 24, or SEQ ID NOs: 300, 301, 302, 303, 23 and 304.

[0026] In various embodiments, antibodies targeting CD47 comprise VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences (according to IMGT): SEQ ID NOs: 25, 26, 27, 28, 29 and 6, SEQ ID NOs: 30, 31, 32, 33, 34 and 12, SEQ ID NOs: 35, 36, 37, 38, 39 and 18, SEQ ID NOs: 40, 41, 42, 43, 44 and 24, SEQ ID NOs: 222, 223, 224, 225, 226 and 215, SEQ ID NOs: 227, 228, 229, 230, 231 and 221, SEQ ID NOs: 305, 41, 42, 43, 44 and 24, or SEQ ID NOs: 306, 307, 308, 309, 44 and 310.

[0027] In various embodiments, antibodies targeting CD47 comprise VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences (according to Chothia): SEQ ID NOs: 45, 46, 47, 48, 29 and 49, SEQ ID NOs: 50, 51, 52, 53, 34 and 54, SEQ ID NOs: 55, 56, 57, 58, 39 and 59, SEQ ID NOs: 60, 61, 62, 62, 44 and 64, SEQ ID NOs: 232, 233, 234, 235, 226 and 236, SEQ ID NOs: 232, 237, 238, 239, 231 and 240, SEQ ID NOs: 311, 61, 62, 63, 44 and 64, or SEQ ID NOs: 312, 313, 314, 315, 44 and 316.

[0028] In various embodiments, antibodies targeting CD47 comprise VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences (according to Honegger): SEQ ID NOs: 65, 66, 67, 68, 69 and 49, SEQ ID NOs: 70, 71, 72, 73, 74 and 54, SEQ ID NOs: 75, 76, 77, 78, 79 and 59, SEQ ID NOs: 80, 81, 82, 83, 84 and 64, SEQ ID NOs: 317, 81, 82, 83, 84 and 64, or SEQ ID NOs: 318, 319, 320, 321, 84 and 316.

[0029] In various embodiments, antibodies targeting CD47 comprise VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences: SEQ ID NOs: 1, 2, 3, 4, 5 and 6 (according to Kabat); SEQ ID NOs: 25, 26, 27, 28, 29 and 6 (according to IMGT), SEQ ID NOs: 45, 46, 47, 48, 29 and 49 (according to Chothia), or SEQ ID NOs: 65, 66, 67, 68, 69 and 49 (according to Honegger).

[0030] In various embodiments, antibodies targeting CD47 comprise VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences: SEQ ID NOs: 7, 8, 9, 10, 11 and 12 (according to Kabat); SEQ ID NOs: 30, 31, 32, 33, 34 and 12 (according to IMGT), SEQ ID NOs: 50, 51, 52, 53, 34 and 54 (according to Chothia), or SEQ ID NOs: 70, 71, 72, 73, 74 and 54 (according to Honegger).

[0031] In various embodiments, antibodies targeting CD47 comprise VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences: SEQ ID NOs: 13, 14, 15, 16, 17, and 18 (according to Kabat); SEQ ID NOs: 35, 36, 37, 38, 39 and 18 (according to IMGT), SEQ ID NOs: 55, 56, 57, 58, 39 and 59 (according to Chothia), or SEQ ID NOs: 80, 81, 82, 83, 84 and 64 (according to Honegger).

[0032] In various embodiments, antibodies targeting CD47 comprise VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences: SEQ ID NOs: 19, 20, 21, 22, 23 and 24 (according to Kabat), SEQ ID NOs: 40, 41, 42, 43, 44 and 24 (according to IMGT), SEQ ID NOs: 60, 61, 62, 62, 44 and 64 (according to Chothia), or SEQ ID NOs: 80, 81, 82, 83, 84 and 64 (according to Honegger).

[0033] In various embodiments, antibodies targeting CD47 comprise VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences: SEQ ID NOs: 210, 211, 212, 213, 214 and 215 (according to Kabat), SEQ ID NOs: 222, 223, 224, 225, 226 and 215 (according to IMGT), SEQ ID NOs: 232, 233, 234, 235, 226 and 236 (from Chothia), or SEQ ID NOs: 241, 242, 243, 244, 245 and 246 (according to Honegger).

[0034] In various embodiments, antibodies targeting CD47 comprise VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences: SEQ ID NOs: 216, 217, 218, 219, 220 and 221 (according to Kabat), SEQ ID NOs: 227, 228, 229, 230, 231 and 221 (according to IMGT), SEQ ID NOs: 232, 237, 238, 239, 231 and 240 (from Chothia), or SEQ ID NOs: 247, 248, 249, 239, 250 and 251 (according to Honegger).

[0035] In various embodiments, antibodies targeting CD47 comprise VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences: SEQ ID NOs: 299, 20, 21, 22, 23 and 24 (according to Kabat); SEQ ID NOs: 305, 41, 42, 43, 44 and 24 (according to IMGT), SEQ ID NOs: 311, 61, 62, 63, 44 and 64 (from Chothia), or SEQ ID NOs: 317, 81, 82, 83, 84 and 64 (according to Honegger).

[0036] In various embodiments, antibodies targeting CD47 comprise VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences: SEQ ID NOs: 300, 301, 302, 303, 23 and 304 (according to Kabat), SEQ ID NOs: 306, 307, 308, 309, 44 and 310 (according to IMGT), SEQ ID NOs: 312, 313, 314, 315, 44 and 316 (from Chothia), or SEQ ID NOs: 318, 319, 320, 321, 84 and 316 (according to Honegger).

[0037] In various embodiments, antibodies targeting CD47 comprise a VH and a VL each comprising the amino acid sequence set forth below, or an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to an amino acid sequence set forth below, respectively. SEQ ID NOs: 85 and 86, SEQ ID NOs: 87 and 88, SEQ ID NOs: 89 and 90, SEQ ID NOs: 91 and 92, SEQ ID NOs: 252 and 253, SEQ ID NOs: 254 and 255, SEQ ID NOs: 322 and 323, or SEQ ID NOs: 324 and 325. Sequence identity can be determined according to the BLAST algorithm (blast.ncbi.nlm.nih.gov / Blast.cgi) using default settings.

[0038] The amino acid sequences of the CDRs and variable regions (VH / VL) of exemplary anti-CD47 antibodies that can be used in the methods of the invention are set forth in Tables A1, A2, A3, A4 and B. [Table A1] [Table A2] [Table A3] [Table A4] [Table B]

[0039] Additional anti-CD47 antibodies useful in the methods of the invention include those disclosed in WO 199727873, WO 199940940, WO 2002092784, WO 2005044857, WO 2009046541, WO 2010070047, WO 2011143624, WO 2012170250, WO 2013109752, WO 2013119714, WO 2014087248, WO 20151918 No. 61, No. 2016022971, No. 2016023040, No. 2016024021, No. 2016081423, No. 2016109415, No. 2016141328, No. 201618 No. 8449, No. 2017027422, No. 2017049251, No. 2017053423, No. 2017121771, No. 2017194634, No. 2017196793, No. 20172 No. 15585, No. 2018075857, No. 2018075960, No. 2018089508, No. 2018095428, No. 2018137705, No. 2018233575, No. 201 No. 9027903, No. 2019034895, No. 2019042119, No. 2019042285, No. 2019042470, No. 2019086573, No. 2019108733, No. 20 Examples of such compounds include those described in No. 19138367, No. 2019144895, No. 2019157843, No. 2019179366, No. 2019184912, No. 2019185717, No. 2019201236, No. 2019238012, No. 2019241732, No. 2020019135, No. 2020036977, No. 2020043188, and No. 2020009725.

[0040] b. An antibody or antigen-binding fragment thereof that binds to SIRPα In various embodiments, the agent that inhibits binding between CD47 and SIRPαCD47 is an antibody or antigen-binding fragment thereof that binds to signal regulatory protein alpha (SIRPα) (NCBI Gene ID: 140885; UniProt P78324). Exemplary antibodies that bind to SIRPα include, but are not limited to, GS-0189 (FSI-189), ES-004, BI765063, ADU1805, and CC-95251.

[0041] In certain embodiments, the antibody may comprise one or more CDRs of 1H9. In some embodiments, the antibody may comprise all of the CDRs of 1H9. In some embodiments, the antibody may comprise one or more variable sequences of 1H9. In some embodiments, the antibody may comprise each variable sequence of 1H9. In some embodiments, the antibody may comprise the heavy chain of 1H9. In some embodiments, the antibody may comprise the light chain of 1H9. In some embodiments, the antibody may comprise the heavy and light chains of 1H9. In some embodiments, the antibody is 1H9.

[0042] In certain embodiments, the antibody may comprise one or more CDRs of 3C2. In some embodiments, the antibody may comprise all CDRs of 3C2. In some embodiments, the antibody may comprise one or more variable sequences of 3C2. In some embodiments, the antibody may comprise each variable sequence of 3C2. In some embodiments, the antibody may comprise a heavy chain of 3C2. In some embodiments, the antibody may comprise a light chain of 3C2. In some embodiments, the antibody may comprise a heavy chain and a light chain of 3C2. In some embodiments, the antibody is 3C2.

[0043] In some embodiments, the antibody may comprise one or more CDRs of 9B11. In some embodiments, the antibody may comprise all of the CDRs of 9B11. In some embodiments, the antibody may comprise one or more variable sequences of 9B11. In some embodiments, the antibody may comprise each variable sequence of 9B11. In some embodiments, the antibody may comprise a heavy chain of 9B11. In some embodiments, the antibody may comprise a light chain of 9B11. In some embodiments, the antibody may comprise a heavy chain and a light chain of 9B11. In some embodiments, the antibody is 9B11.

[0044] In some embodiments, the antibody may comprise one or more CDRs of 7E11. In some embodiments, the antibody may comprise all of the CDRs of 7E11. In some embodiments, the antibody may comprise one or more variable sequences of 7E11. In some embodiments, the antibody may comprise each variable sequence of 7E11. In some embodiments, the antibody may comprise a heavy chain of 7E11. In some embodiments, the antibody may comprise a light chain of 7E11. In some embodiments, the antibody may comprise a heavy chain and a light chain of 7E11. In some embodiments, the antibody is 7E11.

[0045] Additional anti-SIRPα antibodies for use in the method include those disclosed in International Publication Nos. 200140307, ​​2002092784, 2007133811, 2009046541, 2010083253, 2011076781, 2013056352, 2015138600, 2016179399, 2016205042, 2017178653, Examples include those described in No. 2018026600, No. 2018057669, No. 2018107058, No. 2018190719, No. 2018210793, No. 2019023347, No. 2019042470, No. 2019175218, No. 2019183266, No. 2020013170, No. 2020068752, and No. 2020088580.

[0046] In various embodiments, the antibody targeting SIRPα comprises VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences (according to Kabat): SEQ ID NOs: 93, 94, 95, 96, 97 and 98, SEQ ID NOs: 99, 100, 101, 102, 103 and 104, SEQ ID NOs: 99, 100, 105, 102, 103 and 106, SEQ ID NOs: 107, 108, 109, 110, 111 and 112, SEQ ID NOs: 113, 114, 115, 116, 117 and 118, or SEQ ID NOs: 119, 120, 121, 122, 123 and 124.

[0047] In various embodiments, the antibody targeting SIRPα comprises VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences (according to IMGT): SEQ ID NOs: 125, 126, 127, 128, 129 and 98, SEQ ID NOs: 125, 130, 131, 132, 29 and 104, SEQ ID NOs: 125, 130, 133, 132, 29 and 106, SEQ ID NOs: 134, 135, 136, 137, 138 and 112, SEQ ID NOs: 139, 130, 140, 141, 142 and 118, or SEQ ID NOs: 143, 144, 145, 146, 44 and 124.

[0048] In various embodiments, the antibody targeting SIRPα comprises VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences (according to Chothia): SEQ ID NOs: 147, 148, 149, 150, 129 and 151, SEQ ID NOs: 147, 152, 153, 154, 29 and 155, SEQ ID NOs: 147, 152, 156, 154, 29 and 157, SEQ ID NOs: 158, 159, 160, 161, 138 and 162, SEQ ID NOs: 163, 152, 164, 165, 142 and 166, or SEQ ID NOs: 167, 168, 169, 170, 44 and 171.

[0049] In various embodiments, the antibody targeting SIRPα comprises VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences (according to Honegger): SEQ ID NOs: 172, 173, 174, 175, 176 and 151, SEQ ID NOs: 172, 177, 178, 179, 180 and 155, SEQ ID NOs: 172, 181, 182, 179, 180 and 157, SEQ ID NOs: 183, 184, 185, 186, 187 and 162, SEQ ID NOs: 188, 189, 190, 191, 192 and 166, or SEQ ID NOs: 193, 194, 195, 196, 197 and 171.

[0050] In various embodiments, the antibody targeting SIRPα comprises VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences: SEQ ID NOs: 93, 94, 95, 96, 97 and 98 (according to Kabat), SEQ ID NOs: 125, 126, 127, 128, 129 and 98 (according to IMGT), SEQ ID NOs: 147, 148, 149, 150, 129 and 151 (from Chothia), or SEQ ID NOs: 172, 173, 174, 175, 176 and 151 (according to Honegger).

[0051] In various embodiments, the antibody targeting SIRPα comprises VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences: SEQ ID NOs: 99, 100, 101, 102, 103 and 104 (according to Kabat), SEQ ID NOs: 125, 130, 131, 132, 29 and 104 (according to IMGT), SEQ ID NOs: 147, 152, 153, 154, 29 and 155 (from Chothia), or SEQ ID NOs: 172, 177, 178, 179, 180 and 155 (according to Honegger).

[0052] In various embodiments, the antibody targeting SIRPα comprises VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences: SEQ ID NOs: 99, 100, 105, 102, 103 and 106 (according to Kabat); SEQ ID NOs: 125, 130, 133, 132, 29 and 106 (according to IMGT), SEQ ID NOs: 147, 152, 156, 154, 29 and 157 (from Chothia), or SEQ ID NOs: 172, 181, 182, 179, 180 and 157 (according to Honegger).

[0053] In various embodiments, the antibody targeting SIRPα comprises VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences: SEQ ID NOs: 107, 108, 109, 110, 111 and 112 (according to Kabat), SEQ ID NOs: 134, 135, 136, 137, 138 and 112 (according to IMGT), SEQ ID NOs: 158, 159, 160, 161, 138 and 162 (from Chothia), or SEQ ID NOs: 183, 184, 185, 186, 187 and 162 (according to Honegger).

[0054] In various embodiments, the antibody targeting SIRPα comprises VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences: SEQ ID NOs: 113, 114, 115, 116, 117 and 118 (according to Kabat), SEQ ID NOs: 139, 130, 140, 141, 142 and 118 (according to IMGT), SEQ ID NOs: 163, 152, 164, 165, 142 and 166 (according to Chothia), or SEQ ID NOs: 188, 189, 190, 191, 192 and 166 (according to Honegger).

[0055] In various embodiments, the antibody targeting SIRPα comprises VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences: SEQ ID NOs: 119, 120, 121, 122, 123 and 124 (according to Kabat), SEQ ID NOs: 143, 144, 145, 146, 44 and 124 (according to IMGT), SEQ ID NOs: 167, 168, 169, 170, 44 and 171 (from Chothia), or SEQ ID NOs: 193, 194, 195, 196, 197 and 171 (according to Honegger).

[0056] In various embodiments, the antibody targeting SIRPα comprises a VH and a VL each comprising the amino acid sequence shown below, or an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below, respectively. SEQ ID NOs: 198 and 199, SEQ ID NOs: 200 and 201, SEQ ID NOs: 202 and 203, SEQ ID NOs: 204 and 205, SEQ ID NOs: 206 and 207, or SEQ ID NOs: 208 and 209. Sequence identity can be determined according to the BLAST algorithm (blast.ncbi.nlm.nih.gov / Blast.cgi) using default settings.

[0057] The amino acid sequences of the CDRs and variable regions (VH / VL) of exemplary anti-SIRPα antibodies that can be used in the methods of the invention are set forth in Tables C1, C2, C3, C4 and D. [Table C1] [Table C2] [Table C3] [Table C4] [Table D]

[0058] c.SIRPα-Fc fusion protein In various embodiments, the agent that inhibits binding between CD47 and SIRPαCD47 is a SIRPα-Fc fusion protein or a "high affinity SIRPα reagent," which includes SIRPα-derived polypeptides and analogs thereof. High affinity SIRPα reagents are described in WO2013109752, specifically incorporated herein by reference. High affinity SIRPα reagents are variants of native SIRPα proteins. In some embodiments, the high affinity SIRPα reagents are soluble, the polypeptides lack the SIRPα transmembrane domain, and contain at least one amino acid change relative to the wild-type SIRPα sequence, where the amino acid change increases the affinity of the SIRPα polypeptide to bind to CD47, e.g., by decreasing the off-rate by at least 10-fold, at least 20-fold, at least 50-fold, at least 100-fold, at least 500-fold, or more.

[0059] A high affinity SIRPα reagent comprises a sufficient portion of SIRPα (usually between the signal sequence and the transmembrane domain) to bind CD47 with appreciable affinity, e.g., high affinity, or a fragment thereof that retains binding activity. A high affinity SIRPα reagent typically comprises at least the d1 domain of SIRPα with modified amino acid residues to increase affinity. In some embodiments, the SIRPα variant is a fusion protein, e.g., fused in frame with a second polypeptide. In some embodiments, the second polypeptide can increase the size of the fusion protein, e.g., so that the fusion protein is not rapidly cleared from the circulation. In some embodiments, the second polypeptide is a portion or the entirety of an immunoglobulin Fc region. The Fc region aids in phagocytosis by providing an "eat me" signal that enhances the blockade of the "don't eat me" signal provided by the high affinity SIRPα reagent. In other embodiments, the second polypeptide is any suitable polypeptide that is substantially similar to Fc, e.g., providing increased size, a multimerization domain, and / or additional binding or interaction with lg molecules. The amino acid changes that result in increased affinity are localized to the d1 domain, and thus the high affinity SIRPα reagents comprise the d1 domain of human SIRPα with at least one amino acid change relative to the wild-type sequence in the d1 domain. Such high affinity SIRPα reagents optionally include additional amino acid sequences, such as antibody Fc sequences, portions of the wild-type human SIRPα protein other than the d1 domain, including but not limited to residues 150-374 of the native protein or fragments thereof, typically adjacent to the d1 domain. The high affinity SIRPα reagents may be monomeric or multimeric, i.e., dimers, trimers, tetramers, and the like.

[0060] Useful exemplary SIRPα-Fc fusion proteins include ALX-148 (also known as evolupercept, described in WO 2013109752), timdarpacept, TTI-621 or TTI-622 (described in WO 2014094122), SIRPa-F8, JY002-M2G1(N297A), JMT601(CPO107), SS002M91, SIRP alpha-lgG4-Fc-Fc, and hCD172a(SIRPa)-Fc-LIGHT.

[0061] 3. Anti-Trop-2 antibody-drug conjugates (ADCs) The methods described herein involve the co-administration of an agent that inhibits binding between CD47 and SIRPα, and an anti-Trop-2 antibody-drug conjugate (ADC). Trop-2 is tumor associated calcium signaling factor 2 (TACSTD2; NCBI Gene ID: 4070; Uniprot P09758; has alternative acronyms EGP1; GP50; M1S1; EGP-1; TROP2; GA7331 and GA733-1).

[0062] In various embodiments, the drug in the anti-Trop-2 ADC comprises a topoisomerase I inhibitor. In some embodiments, the topoisomerase I inhibitor is selected from irinotecan, topetecan, and SN-38. In some embodiments, the drug conjugate of the anti-Trop-2 ADC has the structural formula mAb-CL2A-SN-38), the structure of which is represented by the following: [ka] (For example, as described in U.S. Pat. No. 7,999,083). In some embodiments, an anti-Trop-2 ADC comprises sacituzumab (hRS7; for example, as disclosed in WO2003074566, Figures 3 and 4). The above is incorporated by reference in its entirety for all purposes.

[0063] Examples of anti-Trop-2 ADCs useful in the present methods include, but are not limited to, sacituzumab govitecan, datopotamab deruxtecan (DS-1062), ESG-401, SKB-264, DAC-02, and BAT-8003.

[0064] In various embodiments, antibodies targeting Trop-2 comprise VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences (according to Kabat): SEQ ID NOs: 258, 259, 260, 261, 262 and 263, or SEQ ID NOs: 264, 265, 266, 267, 262 and 263.

[0065] In various embodiments, antibodies targeting Trop-2 comprise VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences (according to IMGT): SEQ ID NOs: 268, 269, 270, 271, 272 and 263, or SEQ ID NOs: 273, 274, 275, 276, 272 and 263.

[0066] In various embodiments, antibodies targeting Trop-2 comprise VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences (according to Chothia): SEQ ID NOs: 277, 278, 279, 280, 272 and 281, or SEQ ID NOs: 282, 283, 279, 284, 272 and 281.

[0067] In various embodiments, antibodies targeting Trop-2 comprise VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences (according to Honegger): SEQ ID NOs: 285, 286, 287, 288, 289 and 281, or SEQ ID NOs: 290, 291, 292, 293, 294 and 281.

[0068] In various embodiments, antibodies targeting Trop-2 comprise VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences: SEQ ID NOs: 258, 259, 260, 261, 262 and 263 (according to Kabat); SEQ ID NOs: 268, 269, 270, 271, 272 and 263 (according to IMGT), SEQ ID NOs: 277, 278, 279, 280, 272 and 281 (from Chothia), or SEQ ID NOs: 285, 286, 287, 288, 289 and 281 (according to Honegger).

[0069] In various embodiments, antibodies targeting Trop-2 comprise VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, each of which comprises the following amino acid sequences: SEQ ID NOs: 264, 265, 266, 267, 262 and 263 (according to Kabat); SEQ ID NOs: 273, 274, 275, 276, 272 and 263 (according to IMGT), SEQ ID NOs: 282, 283, 279, 284, 272 and 281 (from Chothia), or SEQ ID NOs: 290, 291, 292, 293, 294 and 281 (according to Honegger).

[0070] In various embodiments, antibodies targeting Trop-2 comprise a VH and a VL each comprising the amino acid sequence set forth below, or an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to an amino acid sequence set forth below, respectively. SEQ ID NOs: 295 and 296, or SEQ ID NOs: 297 and 298. Sequence identity can be determined according to the BLAST algorithm (blast.ncbi.nlm.nih.gov / Blast.cgi) using default settings.

[0071] The amino acid sequences of the CDRs and variable regions (VH / VL) of exemplary anti-Trop-2 antibodies that can be used in the methods of the invention are set out in Tables E1, E2, E3, E4 and F. [Table E1] [Table E2] [Table E3] Table E4 [Table F]

[0072] 4. Additional combination agents Additional agents suitable for treating hematological malignancies, such as small molecules, antibodies, adoptive cell therapy, and chimeric antigen receptor T cells (CAR-T), checkpoint inhibitors, and vaccines, may be administered in combination with the agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein. Additional immunotherapeutic agents for hematological malignancies are described in Dong, et al, J Life Sci (Westlake Village). 2019 June; 1(1): 46-52, and Cuesta-Mateos, et al, Front. Immunol. 8: 1936. doi: 10.3389 / fimmu.2017.01936, each of which is incorporated herein by reference in its entirety for all purposes.

[0073] In various embodiments, the agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein can be administered in combination with one or more additional therapeutic agents, such as inhibitory immune checkpoint blockers or inhibitors, stimulatory immune checkpoint stimulators, agonists or activators, chemotherapeutic agents, anti-cancer agents, radiotherapeutic agents, anti-tumor agents, anti-proliferative agents, anti-angiogenic agents, anti-inflammatory agents, immunotherapeutic agents, therapeutic antigen binding molecules (including mono- and multispecific antibodies in any format and fragments thereof (including, but not limited to, DARTs®, Duobodies®, BiTEs®, BiKEs, TriKEs, XmAbs®, TandAbs®, scFvs, Fabs, Fab derivatives), bispecific antibodies, non-immunoglobulin antibody mimetics (including, but not limited to, are further combined with adnectins, affibody molecules, affilins, affimers, affitins, alphabodies, anticalins, peptide aptamers, armadillo repeat proteins (ARMs), atrimers, avimers, designed ankyrin repeat proteins (including DARPins®), finomers, knottins, Kunitz domain peptides, monobodies, and nanoCLAMPs), antibody drug conjugates (ADCs), antibody-peptide conjugates), oncolytic viruses, gene modifiers or editors, cells comprising a chimeric antigen receptor (CAR), e.g., a T cell immunotherapeutic, a NK cell immunotherapeutic, or a macrophage immunotherapeutic, cells comprising a genetically engineered T cell receptor (TCR-T), or any combination thereof.

[0074] In various embodiments, the agents described herein that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 The ADC (e.g., sacituzumab govitecan) may be further combined with one or more additional therapeutic agents, including, but not limited to, an inhibitor, agonist, antagonist, ligand, modulator, stimulator, blocker, activator or suppressor of a target (e.g., a polypeptide or polynucleotide), including, but not limited to, an Abelson murine leukemia viral oncogene homolog 1 gene (ABL, e.g., ABL1), acetyl-CoA carboxylase (e.g., ACC1 / 2), activated CDC kinase (ACK, e.g., ACK1), adenosine deaminase, adenosine receptors (e.g., A2BR, A2aR, A3aR), adenylate cyclase, ADP-ribosyl cyclase-1, adrenocorticotropic hormone receptor (ACTH), aerolysin, AKT1 gene, Alk-5 protein kinase, alkaline phosphatase, leukemia-associated leukemia (ALK) kinase ... Sphatase, alpha 1 adrenergic receptor, alpha 2 adrenergic receptor, alpha-ketoglutarate dehydrogenase (KGDH), aminopeptidase N, AMP-activated protein kinase, anaplastic lymphoma kinase (ALK, e.g., ALK1), androgen receptor, angiopoietins (e.g., ligand-1, ligand-2), angiotensinogen (AGT) gene, mouse thymoma viral oncogene homolog 1 (AKT) protein kinase (e.g., AKT1, AKT2, AKT3), apolipoprotein AI (APOA1) gene, apoptosis inducer, apoptosis proteins (e.g., 1, 2), apoptosis signal-regulating kinase (ASK, e.g., ASK1), arginase (I), arginine deiminase, aromatase, asteroid homolog 1 (ASTE1) gene, ataxia telangiectasia and Rad 3-related (ATR) serine / threonine protein kinase, Aurora protein kinase (e.g., 1, 2), Axl tyrosine kinase receptor, 4-1BB ligand (CD137L), baculovirus IAP repeat-containing 5 (BIRC5) gene, Basigin, B-cell lymphoma 2 (BCL2) gene, Bcl2-binding component 3, Bcl2 protein,BCL2L11 gene, BCR (breakpoint cluster region) protein and gene, beta adrenergic receptor, beta catenin, B lymphocyte antigen CD19, B lymphocyte antigen CD20, B lymphocyte cell adhesion molecule, B lymphocyte stimulatory factor ligand, bone morphogenetic protein-10 ligand, bone morphogenetic protein-9 ligand modulator, brachyury protein, bradykinin receptor, B-Raf proto-oncogene (BRAF), Brc-Abl tyrosine kinase, bromodomain and ectodomain (BET) bromodomain-containing proteins (e.g., BRD2 , BRD3, BRD4), Bruton's tyrosine kinase (BTK), calmodulin, calmodulin-dependent protein kinase (CaMK, e.g., CAMKII), cancer testis antigen 2, cancer testis antigen NY-ESO-1, cancer / testis antigen 1B (CTAG1) gene, cannabinoid receptors (e.g., CB1, CB2), carbonic anhydrase, casein kinase (CK, e.g., CKI, CKII), caspases (e.g., caspase-3, caspase-7, caspase-9), caspase 8 apoptosis-related cysteine ​​peptidase CASP8-FADD-like regulation factors, caspase recruitment domain protein-15, cathepsin G, CCR5 gene, CDK activating kinase (CAK), checkpoint kinases (e.g., CHK1, CHK2), chemokine (CC motif) receptors (e.g., CCR2, CCR4, CCR5, CCR8), chemokine (CXC motif) receptors (e.g., CXCR1, CXCR2, CXCR3 and CXCR4), chemokine CC21 ligand, cholecystokinin CCK2 receptor, human chorionic gonadotropin, c-Kit (tyrosine-protein kinase Kit or CD117), CI SH (cytokine-inducible SH2-containing protein), claudins (e.g., 6, 18), cluster of differentiation (CD), e.g., CD4, CD27, CD29, CD30, CD33, CD37, CD40, CD40 ligand receptor, CD40 ligand, CD40LG gene, CD44, CD45, CD47, CD49b, CD51, CD52, CD55, CD58, CD66e (CEACAM6), CD70 gene, CD74, CD79, CD79b, CD79B gene, CD80, CD95, CD99, CD117, CD122, CDw123, CD134,CDw137, CD158a, CD158b1, CD158b2, CD223, CD276 antigen; clusterin (CLU) gene, clusterin, c-Met (hepatocyte growth factor receptor (HGFR)), complement C3, connective tissue growth factor, COP9 signalosome subunit 5, CSF-1 (colony stimulating factor 1 receptor), CSF2 gene, CTLA-4 (cytotoxic T lymphocyte protein 4) receptor, C-type lectin domain protein 9A (CLEC9A), cyclin D1, cyclin G1, cyclin-dependent kinases (CDKs, e.g., CDK1, CDK12, CDK1B, CDK2-9), cyclooxygenases (e.g., COX1, COX2), CYP2B1 gene, cysteine ​​palmitoyltransferase porcupine, cytochrome P450 11B2, cytochrome P450 17, cytochrome P450 17A1, cytochrome P450 2D6, cytochrome P450 3A4, cytochrome P450 reductase, cytokine signaling-1, cytokine signaling-3, cytoplasmic isocitrate dehydrogenase, cytosine deaminase, cytosine DNA methyltransferase, cytotoxic T lymphocyte protein-4, DDR2 gene, DEAD box helicase 6 (DDX6), death receptor 5 (DR5, TRAILR2), death receptor 4 (DR4, TRAILR1), delta-like protein ligand (e.g. 3, 4), deoxyribonuclease, deubiquitinating enzyme (DUB), Dickkopf-1 ligand, dihydrofolate reductase (DHFR), dihydropyrimidine dehydrogenase, dipeptidyl peptidyl ze IV, discoidin domain receptor (DDR, e.g. DDR1), diacylglycerol kinase zeta (DGKZ), DNA binding proteins (e.g. HU-beta), DNA-dependent protein kinase, DNA gyrase, DNA methyltransferase, DNA polymerase (e.g. alpha), DNA primase, dUTP pyrophosphatase, L-dopachrome tautomerase, E3 ubiquitin-protein ligase (e.g. RNF128, CBL-B), echinoderm microtubule-like protein 4, EGFR tyrosine kinase receptor, elastase, elongation factor 1 alpha 2, elongation factor 2, endoglin, endonuclease, endoplasmic reticulum aminopeptidase (ERAP,e.g., ERAP1, ERAP2), endoplasmin, endosialin, endostatin, endothelin (e.g., ET-A, ET-B), enhancer of zest homolog 2 (EZH2), ephrin (EPH) tyrosine kinase (e.g., Epha3, Ephb4), ephrin B2 ligand, epidermal growth factor, epidermal growth factor receptor (EGFR), epidermal growth factor receptor (EGFR) gene, epigen, epithelial cell adhesion molecule (EpCAM), Erb-b2 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2) tyrosine kinase receptor, Erb-b3 tyrosine kinase receptor, Erb-b4 tyrosine kinase receptor, E-selectin, estradiol 17 beta dehydrogenase, estrogen receptor (e.g., alpha, beta), estrogen-related linked receptor, eukaryotic translation initiation factor 5A (EIF5A) gene, exportin 1, extracellular signal-related kinase (e.g. 1, 2), extracellular signal-regulated kinase (ERK), hypoxia-inducible factor prolyl hydroxylase (HIF-PH or EGLN), factor (e.g. Xa, VIIa), farnesoid x receptor (FXR), Fas ligand, fatty acid synthase (FASN), ferritin, FGF-2 ligand, FGF-5 ligand, fibroblast growth factor (FGF, e.g. FGF1, FGF2, FGF4), fibronectin, focal adhesion kinase (FAK, e.g. FAK2), folate hydrolase prostate specific membrane antigen 1 (FOLH1), folate receptor (e.g. alpha), folate, folate transporter 1, FYN tyrosine kinase, paired basic amino acid cleavage enzyme (PACE) basic amino acid cleaving enzyme, FURIN), beta-glucuronidase, galactosyltransferase, galectin-3, ganglioside GD2, glucocorticoid, glucocorticoid-inducible TNFR-related protein GITR receptor, glutamate carboxypeptidase II, glutaminase, glutathione S-transferase P, glycogen synthase kinase (GSK, e.g., 3-beta), glypican 3 (GPC3), gonadotropin-releasing hormone (GNRH), granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor, granulocyte colony-stimulating factor (GCSF) ligand, growth factor receptor-bound protein 2 (GRB2),Grp78 (glucose-regulated protein of 78 kDa) calcium-binding protein, molecular chaperone groEL2 gene, heme oxygenase 1 (HO1), heme oxygenase 2 (HO2), heat shock proteins (e.g. 27, 70, 90 alpha, beta), heat shock protein genes, heat-stable enterotoxin receptor, hedgehog protein, heparanase, hepatocyte growth factor, HERV-H LTR-associated protein 2, hexose kinase, histamine H2 receptor, histone methyltransferase (DOT1L), histone deacetylase (HDAC, e.g. 1, 2, 3, 6, 10, 11), histone H1, histone H3, HLA class I antigen (A-2 alpha), HLA class II antigen, HLA class I antigen alpha G (HLA-G), non-classical HLA, homeobox protein NANOG, HSPB1 gene, human leukocyte antigen (HLA), human papillomavirus (e.g. E6, E7) proteins, hyaluronic acid, hyaluronidase, hypoxia-inducible factor-1 alpha (HIF1α), Imprinted Maternally Expressed Transcript (H19) gene, mitogen-activated protein kinase 1 (MAP4K1), tyrosine-protein kinase HCK, I-kappa-B kinase (IKK, e.g., IKKbe), IL-1 alpha, IL-1 beta, IL-12, IL-12 gene, IL-15, IL-17, IL-2 gene, IL-2 receptor alpha subunit, IL-2, IL-3 receptor, IL-4, IL-6, IL-7, IL-8, immunoglobulins (e.g., G, G1, G2, K, M), immunoglobulin Fc receptor, immunoglobulin gamma Fc receptor (e.g., I, I II, IIIA), indoleamine 2,3-dioxygenase (IDO, e.g. IDO1 and IDO2), indoleamine pyrrole 2,3-dioxygenase 1 inhibitors, insulin receptor, insulin-like growth factors (e.g. 1, 2), integrin alpha-4 / beta-1, integrin alpha-4 / beta-7, integrin alpha-5 / beta-1, integrin alpha-V / beta-3, integrin alpha-V / beta-5, integrin alpha-V / beta-6, intercellular adhesion molecule 1 (ICAM-1), interferons (e.g. alpha,alpha 2, beta, gamma), interferon-inducible protein absent in melanoma 2 (AIM2), interferon type I receptor, interleukin 1 ligand, interleukin 13 receptor alpha 2, interleukin 2 ligand, interleukin-1 receptor-associated kinase 4 (IRAK4), interleukin-2, interleukin-29 ligand, , interleukin 35 (IL-35), isocitrate dehydrogenase (e.g., IDH1, IDH2), Janus kinase (JAK, e.g., JAK1, JAK2), Jun N-terminal kinase, kallikrein-related peptidase 3 (KLK3) gene, killer cell Ig-like receptor, kinase insert domain receptor (KDR), kinesin-like protein KIF11, Kirsten rat sarcoma viral oncogene homolog (KRAS) gene, kisspeptin (KiSS-1) receptor, KIT gene, v-kit Hardy-Zuckerman Feline sarcoma viral oncogene homolog (KIT) tyrosine kinase, lactoferrin, lanosterol-14 demethylase, LDL receptor-related protein-1, leukocyte immunoglobulin-like receptor subfamily B member 1 (ILT2), leukocyte immunoglobulin-like receptor subfamily B member 2 (ILT4), leukotriene A4 hydrolase, listeriolysin, L-selectin, progesterone receptor lyase, lymphocyte activation gene 3 protein (LAG-3), lymphocyte antigen 75, lymphocyte function antigen-3 receptor, lymphocyte-specific protein tyrosine kinase (LCK), lymphotactin, Lyn (Lck / Yes) novel) tyrosine kinase, lysine demethylase (e.g. KDM1, KDM2, KDM4, KDM5, KDM6, A / B / C / D), lysophosphatidic acid-1 receptor, lysosomal-associated membrane protein family (LAMP) genes, lysyl oxidase homolog 2, lysyl oxidase protein (LOX), 5-lipoxygenase (5-LOX), hematopoietic progenitor kinase 1 (HPK1), hepatocyte growth factor receptor (MET) gene, macrophage colony-stimulating factor (MCSF) ligand, macrophage migration inhibitory factor, MAGEC1 gene, MAGEC2 gene, major vault protein, MAPK-activated protein kinase (e.g. MK2), Mas-related G-protein-coupled receptor, matrix metalloproteinase (MMP, e.g. MMP2, MMP9), Mcl-1 differentiation protein, Mdm2 p53 binding protein, Mdm4 protein, Melan-A (MART-1) melanoma antigen, melanocyte protein Pmel 17, melanocyte stimulating hormone ligand, melanoma antigen family A3 (MAGEA3) gene,Melanoma-associated antigens (e.g., 1, 2, 3, 6), membrane copper amine oxidase, mesothelin, MET tyrosine kinase, metabotropic glutamate receptor 1, metalloreductase STEAP1 (six transmembrane epithelial antigen of the prostate 1), metastin, methionine aminopeptidase-2, methyltransferase, mitochondrial 3-ketoacyl-CoA thiolase, mitogen-activated protein kinase (MAPK), mitogen-activated protein kinase (MEK, e.g., MEK1, MEK2), mTOR (mechanistic target of rapamycin (serine / threonine kinase), mTOR complex (e.g., 1, 2), mucins (e.g., 1, 5A, 16), mut T homolog (MTH, e.g., MTH1), Myc proto-oncogene protein, myeloid cell leukemia 1 (MCL1) gene, myristoylated alanine-rich protein kinase C substrate (MARCKS) protein, NAD ADP-ribosyltransferase, natriuretic peptide receptor C, neural cell adhesion molecule 1, neurokinin 1 (NK1) receptor, neurokinin receptor, neuropilin 2, NF-kappa B-activating protein, NIMA-related kinase 9 (NEK9), nitric oxide synthase, NK cell receptor, NK3 receptor, NKG2 AB-activating NK receptor, NLRP3 (NACHT LRR PYD domain protein 3) modulator, noradrenaline transporter, Notch (e.g., Notch-2 receptor, Notch-3 receptor, Notch-4 receptor), nuclear erythroid 2-related factor 2, nuclear factor (NF) kappa B, nucleolin, nucleophosmin, nucleophosmin anaplastic lymphoma kinase (NPM-ALK), 2-oxoglutarate dehydrogenase, 2,5-oligoadenylate synthetase, O-methylguanine DNA methyltransferase, opioid receptor (e.g., delta), ornithine decarboxylase, orotate phosphoribosyltransferase, orphan nuclear hormone receptor NR4A1, osteocalcin, osteoclast differentiation factor, osteopontin, OX-40 (tumor necrosis factor receptor superfamily member 4 TNFRSF4, or CD134) receptor, P3 protein, p38 kinase, p38 MAP kinase, p53 tumor suppressor protein, parathyroid hormone ligand, peroxisome proliferator-activated receptor (PPAR,alpha, delta, gamma), P-glycoprotein (e.g. 1), phosphatase and tensin homolog (PTEN), phosphatidylinositol 3-kinase (PI3K), phosphoinositide-3 kinase (PI3K, e.g. alpha, delta, gamma), phosphorylase kinase (PK), PKN3 gene, placental growth factor, platelet-derived growth factor (PDGF, e.g. alpha, beta), platelet-derived growth factor (PDGF, e.g. alpha, beta), multidrug resistance transporter, Plexin B1, PLK1 gene, polo-like kinase (PLK), polo-like kinase 1, poly(ADP-ribose) polymerase (PARP, e.g. PARP1, PARP2 and PARP3, PARP7, and mono-PARPs), selectively expressed antigen in melanoma (PRAME) gene, prenyl-binding protein (PrPB), putative transcription factor (Probable transcription factor factor) PML, progesterone receptor, programmed cell death 1 (PD-1), programmed cell death ligand 1 inhibitor (PD-L1), prosaposin (PSAP) gene, prostanoid receptor (EP4), prostaglandin E2 synthase, prostate-specific antigen, prostatic acid phosphatase, proteasome, protein E7, protein farnesyltransferase, protein kinase (PK, e.g. A, B, C), protein tyrosine kinase, protein tyrosine phosphatase adenosine kinase beta, proto-oncogene serine / threonine-protein kinase (PIM, e.g. PIM-1, PIM-2, PIM-3), P-selectin, purine nucleoside phosphorylase, purinergic receptor P2X ligand-gated ion channel 7 (P2X7), pyruvate dehydrogenase (PDH), pyruvate dehydrogenase kinase, pyruvate kinase (PYK), 5-alpha-reductase, Raf protein kinase (e.g. 1, B), RAF1 gene, Ras gene, Ras GTPase, RET gene, Ret tyrosine kinase receptor, retinoblastoma-associated protein, retinoic acid receptor (e.g. gamma), retinoid X receptor, Rheb (Ras homolog enriched in brain) GTPase, Rho (Ras homolog)-associated protein kinase 2, ribonuclease,Ribonucleotide reductase (e.g., M2 subunit), ribosomal protein S6 kinase, RNA polymerase (e.g., I, II), Ron (Recepteur d'Origine Nantais) tyrosine kinase, ROS1 (ROS proto-oncogene 1, receptor tyrosine kinase) gene, Ros1 tyrosine kinase, Runt-related transcription factor 3, gamma-secretase, S100 calcium-binding protein A9, sarcoplasmic reticulum calcium ATPase, second mitochondrial-derived activator of caspases (SMAC) protein, secreted frizzled-associated protein-2, secreted phospholipase A2, semaphorin-4D, serine proteases, serine / threonine kinases (STKs), serine Threonine / threonine-protein kinase (TBK, e.g., TBK1), signal transducer and activator of transcription (STAT, e.g., STAT-1, STAT-3, STAT-5), signal transducing lymphocyte activation molecule (SLAM) family member 7, six transmembrane epithelial antigen of the prostate (STEAP) genes, SL cytokine ligand, smoothened (SMO) receptor, sodium iodide symporter, sodium phosphate symporter 2B, somatostatin receptors (e.g., 1, 2, 3, 4, 5), sonic hedgehog protein, Son of sevenless (SOS), specific protein 1 (Sp1) transcription factor, sphingomyelin synthase, sphingosine kinase (eg 1, 2), sphingosine-1-phosphate receptor-1, spleen tyrosine kinase (SYK), SRC gene, Src tyrosine kinase, Stabilin-1 (STAB1), STAT3 gene, steroid sulfatase, stimulator of interferon genes (STING) receptor, stimulator of interferon genes protein, stromal cell-derived factor 1 ligand, SUMO (small ubiquitin-like modifier), superoxide dismutase, suppressor of cytokine signaling modulators (SOCS), survivin protein, synapsin 3, syndecan-1, synuclein alpha, T cell surface glycoprotein CD28, tank-binding kinase (TBK), TATA box-binding protein-associated factor RNA polymerase I subunit B (TAF1B) gene, T cell CD3 glycoprotein zeta chain, T cell differentiation antigen CD6,T cell immunoglobulin and mucin domain containing-3 (TIM-3), T cell surface glycoprotein CD8, Tec protein tyrosine kinase, Tek tyrosine kinase receptor, telomerase, telomerase reverse transcriptase (TERT) gene, tenascin, three prime repair exonuclease 1 (TREX1), three prime repair exonuclease 2 (TREX2), thrombopoietin receptor, thymidine kinase, thymidine phosphorylase, thymidylate synthase, thymosin (e.g. alpha 1), thyroid hormone receptor, thyrotropin ... mon receptor, tissue factor, tumor necrosis factor-related apoptosis-inducing ligand, TNFR1-associated death domain protein, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor, TNFSF11 gene, TNFSF9 gene, Toll-like receptors (TLR, e.g., 1-13), topoisomerases (e.g., I, II, III), transcription factors, transferases, transferrin (TF), transforming growth factor alpha (TGFα), transforming growth factor beta (TGFB) and their isoforms, TGF beta 2 ligand, tra transforming growth factor TGF-β receptor kinase, transglutaminase, translocation-associated protein, transmembrane glycoprotein NMB, Trop-2 calcium signal transducer, trophoblast glycoprotein (TPBG) gene, trophoblast glycoprotein, tropomyosin receptor kinase (Trk) receptor (e.g. TrkA, TrkB, TrkC), tryptophan 2,3-dioxygenase (TDO), tryptophan 5-hydroxylase, tubulin, tumor necrosis factor (TNF, e.g. alpha, beta), tumor necrosis factor 13C receptor, Tumor progression locus 2 (TPL2), tumor protein 53 (TP53) gene, tumor suppressor candidate 2 (TUSC2) gene, tumor-specific neoantigen, tyrosinase, tyrosine hydroxylase, tyrosine kinase (TK), tyrosine kinase receptor, tyrosine kinase with immunoglobulin-like and EGF-like domains (TIE) receptor, tyrosine protein kinase ABL1 inhibitor, ubiquitin, ubiquitin carboxyl hydrolase isozyme L5, ubiquitin thioesterase-14, ubiquitin-conjugating enzyme E2I (UBE2I, UBC9),Ubiquitin-specific processing protease 7 (USP7), urease, urokinase plasminogen activator, uteroglobin, vanilloid VR1, vascular cell adhesion protein 1, vascular endothelial growth factor receptor (VEGFR), V-domain Ig inhibitor of T cell activation (VISTA), VEGF-1 receptor, VEGF-2 receptor, VEGF-3 receptor, VEGF-A, VEGF-B, vimentin, vitamin D3 receptor, proto-oncogene tyrosine-linked protein-1 (PTP-1), and kinase, Mer (Mer tyrosine kinase receptor modulator), YAP (Yes-associated protein modulator), Wee-1 protein kinase, Werner syndrome RecQ-like helicase (WRN), Wilms tumor antigen 1, Wilms tumor protein, WW domain-containing transcription regulator protein 1 (TAZ), X-linked inhibitor of apoptosis protein, zinc finger protein transcription factor, or a combination thereof.

[0075] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are combined with one or more additional therapeutic agents, which may be categorized by mechanism of action, for example, the following classes of therapeutic agents: antimetabolites / anticancer drugs, such as pyrimidine analogs floxuridine, capecitabine, cytarabine, CPX-351 (liposomal cytarabine, daunorubicin), and TAS-118; alpha 1 adrenergic receptor / alpha 2 adrenergic receptor antagonists, such as phenoxybenzamine hydrochloride (injectable, pheochromocytoma); androgen receptor antagonists, such as nilutamide; anti-cadherin antibodies, such as HKT-288; anti-leucine-rich repeat containing 15 ( ... 15, LRRC15) antibodies, such as ABBV-085.ARGX-110; angiotensin receptor blockers, nitric oxide donors; antisense oligonucleotides, such as AEG35156, IONIS-KRAS-2.5Rx, EZN-3042, RX-0201, IONIS-AR-2.5Rx, BP-100 (plexigenesis), IONIS-STAT3-2.5Rx; anti-angiopoietin (ANG)-2 antibodies, such as MEDI3617 and LY3127804; anti-ANG-1 / ANG-2 antibodies, such as AMG-780; anti-CSF1R antibodies, such as anti-endoglin antibodies, e.g., TRC105 (carotuximab); anti-ERBB antibodies, e.g., CDX-3379, HLX-02, seribantumab; anti-HER2 antibodies, e.g., HERCEPTIN® (trastuzumab), trastuzumab biosimilar, margetuximab, MEDI4276, BAT-8001, pertuzumab (Perjeta), RG6264, ZW25 (bispecific HER2-directed antibody targeting extracellular domains 2 and 4; Cancer Discov. 2019 Jan;9(1):8;PMID:30504239); anti-HLA-DR antibodies, e.g., IMMU-114;Anti-IL-3 antibodies, such as JNJ-56022473, anti-TNF receptor superfamily member 18 (TNFRSF18, GITR; NCBI Gene Number: 8784) antibodies, such as MK-4166, MEDI1873, FPA-154, INCAGN-1876, TRX-518, BMS-986156, MK-1248, GWN-323; and those described in, for example, International Patent Publication Nos. 2017 / 096179, 2017 / 096276, 2017 / 096189, and 2018 / 089628; anti-EphA3 antibodies, such as antibodies, e.g., KB-004; anti-CD37 antibodies, e.g., otlertuzumab (TRU-016); anti-FGFR-3 antibodies, e.g., LY3076226, B-701; anti-FGFR-2 antibodies, e.g., GAL-F2; anti-C5 antibodies, e.g., ALXN-1210; anti-EpCAM antibodies, e.g., VB4-845; anti-CEA antibodies, e.g., RG-7813; anti-carcinoembryonic-antigen-related-cell-adhesion-molecule-6 (CEACAM6, CD66C) antibodies, e.g., antibodies, e.g., BAY-1834942, NEO-201 (CEACAM5 / 6); anti-GD2 antibodies, e.g., APN-301, anti-interleukin 17 (IL-17) antibodies, e.g., CJM-112; anti-interleukin-1 beta antibodies, e.g., canakinumab (ACZ885), VPM087; anti-carbonic anhydrase 9 (CA9, CAIX) antibodies, e.g., TX-250; anti-mucin 1 (MUC1) antibodies, e.g., gatipotuzumab, Mab-AR-20.5; anti-KMA antibodies, e.g., MDX-1097; anti-CD55 antibodies, e.g., PAT-SC1, anti-c- Met antibodies, e.g., ABBV-399; anti-PSMA antibodies, e.g., ATL-101; anti-CD100 antibodies, e.g., VX-15, anti-EPHA3 antibodies, e.g., fibatuzumab; anti-APRIL antibodies, e.g., BION-1301; anti-fibroblast activation protein (FAP) / IL-2R antibodies, e.g., RG7461; anti-fibroblast activation protein (FAP) / TRAIL-R2 antibodies, e.g., RG7386; anti-fucosyl-GM1 antibodies, BMS-986012, etc.; anti-IL-8 (interleukin-8) antibodies, e.g., HuMax-Inflam;anti-myostatin inhibitors, e.g., landgrozumab; anti-delta-like protein ligand 3 (DDL3) antibodies, e.g., rovalpituzumab tesirin; anti-DLL4 (delta-like ligand 4) antibodies, e.g., demcizumab; anti-clusterin antibodies, e.g., AB-16B5; anti-ephrin-A4 (EFNA4) antibodies, e.g., PF-06647263; anti-mesothelin antibodies, e.g., BMS-986148, anti-MSLN-MMAE; anti-sodium phosphate cotransporter 2B (NaP2B) antibodies, such as rifastuzumab; anti-TGFβ antibodies, e.g., SAR439459; anti-tran Transforming growth factor-beta (TGF-beta) antibodies, e.g., ABBV-151, LY3022859, NIS793, XOMA089; purine analogs, folate antagonists (e.g., pralatrexate), cladribine, pentostatin, fludarabine, and related inhibitors; natural products, e.g., vinca alkaloids (vinblastine, vincristine), and microtubule disruptors, e.g., taxanes (paclitaxel, docetaxel), vinblastine, nocodazole, epothilones, vinorelbine (NAVELBINE®), and elastase. Antiproliferative / antimitotic agents, including hypodophyllotoxins (etoposide, teniposide); DNA damaging agents, such as actinomycin, amsacrine, busulfan, carboplatin, chlorambucil, cisplatin, cyclophosphamide (CYTOXAN®), dactinomycin, daunorubicin, doxorubicin, DEBDOX, epirubicin, ifosfamide, melphalan, mechlorethamine, mitomycin C, mitoxantrone, nitrosoureas, procarbazine, taxol, taxotere, teniposide, etoposide, and triethylamine. lenthiophosphoramides; hypomethylating agents such as guadecitabine (SGI-110), oral decitabine and cedazuridine (ASTX727); antibiotics such as dactinomycin, daunorubicin, doxorubicin, idarubicin, anthracyclines, mitoxantrone, bleomycin, primycin (mithramycin); enzymes such as L-asparaginase, which metabolizes L-asparagine throughout the body and eliminates cells that do not have the ability to synthesize asparagine themselves; DNAi oligonucleotides targeting Bcl-2, such as PNT2258;Agents that activate or reactivate latent human immunodeficiency virus (HIV), such as panobinostat and romidepsin; asparaginase stimulators, such as crisantaspase (Erwinase®) and GRASPA (ERY-001, ERY-ASP), calaspargase pegol, pegaspargase; pan-Trk, ROS1, and ALK inhibitors, such as entrectinib, TPX-0005; anaplastic lymphoma kinase (ALK) inhibitors, such as alectinib, ceritinib, Alecensa (RG7853), ALUNBRIG (registered trademark), (Brigatinib); antiproliferative / antimitotic alkylating agents such as nitrogen mustard cyclophosphamide and analogs (e.g., melphalan, chlorambucil, hexamethylmelamine, thiotepa), alkylnitrosoureas (e.g., carmustine) and analogs, streptozocin, and triazenes (e.g., dacarbazine); antiproliferative / antimitotic antimetabolites such as folic acid analogs (methotrexate); platinum coordination complexes (e.g., cisplatin, oxiloplatinim, and carboplatin), procarbazine, hydroxyurea, mitotane , and aminoglutethimide; hormones, hormone analogues (e.g., estrogen, tamoxifen, goserelin, bicalutamide, and nilutamide), and aromatase inhibitors (e.g., letrozole and anastrozole); antiplatelet agents; anticoagulants, such as heparin, synthetic heparin salts, and other inhibitors of thrombin; fibrinolytic agents, such as tissue plasminogen activator, streptokinase, urokinase, aspirin, dipyridamole, ticlopidine, and clopidogrel; antimigratory agents; antisecretory agents (e.g., breveldin, ); immunosuppressants such as tacrolimus, sirolimus, azathioprine, and mycophenolate; growth factor inhibitors and vascular endothelial growth factor inhibitors; fibroblast growth factor inhibitors such as FPA14; AMP-activated protein kinase stimulators such as metformin hydrochloride; ADP-ribosyl cyclase-1 inhibitors such as daratumumab (DARZALEX®); caspase recruitment domain protein-15 stimulators such as mifamurtide (liposomal); CCR5 chemokine antagonists such as MK-7690 (vicriviroc);CDC7 protein kinase inhibitors, such as TAK-931; cholesterol side chain cleavage enzyme inhibitors, such as ODM-209; dihydropyrimidine dehydrogenase / orotate phosphoribosyltransferase inhibitors, such as cefezone (tegafur + gimeracil + oteracil potassium); DNA polymerase / ribonucleotide reductase inhibitors, such as clofarabine; DNA interference oligonucleotides, such as PNT2258, AZD-9150; estrogen receptor modulators, such as bazedoxifene; estrogen receptor agonists / progesterone receptor antagonists, such as TRI-CYCLEN LO (norethindrone + ethinyl estradiol); HLA class I antigen A-2 alpha modulators, such as FH-MCVA2TCR; HLA class I antigen A-2 alpha / MART-1 melanoma antigen modulators, such as MART-1 F5 TCR engineered PBMC; human granulocyte colony stimulating factor, e.g., PF-06881894; GNRH receptor agonists, e.g., leuprorelin acetate, leuprorelin acetate sustained release depot (ATRIGEL), triptorelin pamoate, goserelin acetate; GNRH receptor antagonists, e.g., elagolix, relugolix, degarelix; endoplasmin modulators, e.g., anlotinib; H+K+ATPase inhibitors, e.g., omeprazole, esomeprazole; ICAM-1 / CD55 modulators, e.g., cavatak (V-937); IL-15 / IL-12 modulators, e.g., SAR441000; interleukin 23A inhibitors, e.g., guselkumab; lysine-specific histone demethylase 1 inhibitors, e.g., CC-90011; IL-12 mRNAs, e.g., MEDI1191; RIG-I modulators, e.g., RGT-100; NOD2 modulators, such as SB-9200 and IR-103; progesterone receptor agonists, e.g., levonorgestrel; protein cereblon modulators, such as CC-92480, CC-90009; protein cereblon modulators / DNA binding protein Ikaros inhibitors / zinc finger binding protein Aiolos inhibitors, e.g., iverdomid;Retinoid X receptor modulators, such as alitretinoin, bexarotene (oral formulations); RIP-1 kinase inhibitors, such as GSK-3145095; selective estrogen receptor degraders, such as AZD9833; SUMO inhibitors, such as TAK-981; thrombopoietin receptor agonists, such as eltrombopag; thyroid hormone receptor agonists, such as levothyroxine sodium; TNF agonists, such as tasonermin; tyrosine phosphatase substrate 1 inhibitors, such as CC-95251; HER2 inhibitors, such as neratinib, tucatinib (ONT-380); EGFR / E; rbB2 / Ephb4 inhibitors, e.g., tecevatinib; EGFR / HER2 inhibitors, e.g., TAK-788; EGFR family tyrosine kinase receptor inhibitors, e.g., DZD-9008; EGFR / ErbB-2 inhibitors, e.g., balitinib; mutation-selective EGFR inhibitors such as PF-06747775, EGF816 (nazartinib), ASP8273, ACEA-0010, BI-1482694; epha2 inhibitors, e.g., MM-310, polycomb protein (EED) inhibitors, e.g., MAK683; DHFR inhibitors / folate transporter 1 modulators / folate receptor antagonists, e.g., pralatrexate; DHFR / GAR transformylase / thymidylate synthase / transferase inhibitors, e.g., pemetrexed disodium; p38 MAP kinase inhibitors, e.g., ralimetinib; PRMT inhibitors, e.g., MS203, PF-06939999, GSK3368715, GSK3326595; sphingosine kinase 2 (SK2) inhibitors, e.g., opaganib; nuclear erythroid 2-related factor 2 stimulators, e.g., omaveloxolone (RTA-408); tropomyosin receptor kinase (TRK) inhibitors, e.g., LOXO-195, ONO-7579; mucin 1 inhibitors, e.g., GO-203-2C; MARCKS protein inhibitors, e.g., BIO-11006, folate antagonists such as arfolitixolin, e.g.; galectin-3 inhibitors, e.g., GR-MD-02; phosphorylated P68 inhibitors anti-inflammatory agents, such as RX-5902; CD95 / TNF modulators, such as ofranelgene obadenovec; pan-PIM kinase inhibitors, such as INCB-053914; IL-12 gene stimulators, such as EGEN-001, taboquinogen terce plasmid; heat shock protein HSP90 inhibitors, such as TAS-116, PEN-866; VEGF / HGF antagonists, such as MP-0250; VEGF ligand inhibitors, such as bevacizumab biosimilars; VEGF receptor antagonists / VEGF ligand inhibitors, such as ramucirumab; VEGF-1 / VEGF-2 / VEGF-3 receptor antagonists, such as fruquintinib;VEGF-1 / VEGF-2 receptor modulators, e.g., HLA-A2402 / HLA-A0201 restricted epitope peptide vaccines; placental growth factor ligand inhibitors / VEGF-A ligand inhibitors, e.g., aflibercept; SYK tyrosine kinase / JAK tyrosine kinase inhibitors such as ASN-002; Trk tyrosine kinase receptor inhibitors, e.g., larotrectinib sulfate; JAK3 / JAK1 / TBK1 kinase inhibitors, e.g., CS-12912; IL-24 antagonists, e.g., AD-IL24; NLRP3 (NACHT LRR PYD domain protein 3) modulators, e.g., BMS-986299; RIG-I agonists, e.g., RGT-100; aerolysin stimulators, e.g., topsalisin; P-glycoprotein 1 inhibitors, e.g., HM-30181A; CSF-1 antagonists, e.g., ARRY-382, BLZ-945; CCR8 inhibitors such as JTX-1811, I-309, SB-649701, HG-1013, RAP-310; anti-mesothelin antibodies, e.g., SEL-403; thymidine kinase stimulators, e.g., agratimagenbesadenovec; Polo-like kinase 1 inhibitors, e.g., PCM-075, onvansertib; NAE inhibitors, e.g., pevonedistat (MLN-4924); Trop-2 inhibitors, pleiotropic pathway modulators, such as avadomide (CC-122); amyloid protein binding protein-1 inhibitors / ubiquitin ligase modulators, such as sacituzumab govitecan; FoxM1 inhibitors, such as thiostreptopton; UBA1 inhibitors, such as TAK-243, Src tyrosine kinase inhibitors, such as VAL-201; VDAC / HK inhibitors, such as VDA-1102; Elf4a inhibitors, such as rohitinib, eFT226; TP53 gene stimulators, such as ad-p53; retinoic acid receptor agonists, such as tretinoin; retinoic acid receptor alpha (Retinoic acid receptor alpha (RARα) inhibitors, such as SY-1425; SIRT3 inhibitors, such as YC8-02, stromal cell-derived factor 1 ligand inhibitors, such as oraptest pegol (NOX-A12);IL-4 receptor modulators, e.g., MDNA-55; arginase I stimulators, e.g., PEGylliginase; topoisomerase I inhibitors, e.g., irinotecan hydrochloride, Onivyde; topoisomerase I inhibitors / hypoxia inducible factor-1 alpha inhibitors, e.g., PEG-SN38 (filtecan pegol); hypoxia inducible factor-1 alpha inhibitors, e.g., PT-2977, PT-2385; CD122 (IL-2 receptor) agonists agonists, such as proleukin (aldesleukin, IL-2); pegylated IL-2 (e.g., NKTR-214); modified variants of IL-2 (e.g., THOR-707); TLR7 / TLR8 agonists, such as NKTR-262; TLR7 agonists, such as DS-0509, GS-9620, LHC-165, TMX-101 (imiquimod); p53 tumor suppressor protein stimulators, such as quevetrin; Mdm4 / Mdm2 p53 binding protein inhibitors, e.g., ALRN-6924; kinesin spindle protein (KSP) inhibitors, e.g., filanesib (ARRY-520); CD80-Fc fusion protein inhibitors, e.g., FPT-155; menin and mixed leukemia (MLL) inhibitors, e.g., KO-539; liver x receptor agonists, e.g., RGX-104; IL-10 agonists, e.g., pegylodecaquin (AM-0010); VEGFR / PDGFR inhibitors, e.g., borolanib; IRAK4 inhibitors, e.g., CA-4948, anti-TLR-2 antibodies, e.g., OPN-305, calmodulin modulators such as CBP-501;

[0076] glucocorticoid receptor antagonists, e.g., Relacorilant (CORT-125134); second mitochondria-derived activator of caspases (SMAC) protein inhibitors, e.g., BI-891065; lactoferrin modulators, e.g., LTX-315; KIT proto-oncogene, receptor tyrosine kinase (KIT) inhibitors, e.g., PLX-9486; platelet-derived growth factor receptor alpha (PDGFRA) / KIT proto-oncogene, receptor tyrosine kinase (KIT) mutant-specific antagonists / inhibitors, e.g., BLU-285, DCC-2618; exportin 1 inhibitors, e.g., Ertanexo CHST15 gene inhibitors, e.g., STNM-01; somatostatin receptor antagonists, e.g., OPS-201; CEBPA gene stimulators, e.g., MTL-501; DKK3 gene modulators, e.g., MTG-201; chemokine (CXCR1 / CXCR2) inhibitors, e.g., SX-682; p70s6k inhibitors, e.g., MSC2363318A, methionine aminopeptidase 2 (MetAP2) inhibitors, e.g., M8891, APL-1202; arginine N-methyl lysyltransferase 5 inhibitors, e.g., GSK-3326595; CD71 modulators, e.g., CX-2029 (ABBV-2029); ATM (ataxia telangiectasia) inhibitors, e.g., AZD0156, AZD1390; CHK1 inhibitors, e.g., GDC-0575, LY2606368 (prexasertib), SRA737, RG7741 (CHK1 / 2); CXCR4 antagonists, e.g., BL-8040, LY2510924, blixafol (TG-0054), X4 P-002, X4P-001-IO, plerixafor; EXH2 inhibitors such as GSK2816126, KDM1 inhibitors such as ORY-1001, IMG-7289, INCB-59872, GSK-2879552; CXCR2 antagonists such as AZD-5069; DNA-dependent protein kinase inhibitors such as MSC2490484A (nedisertib), VX-984, AsiDNA (DT-01); Protein kinase C (PKC) inhibitors such as LXS-196,sotrastaurin; selective estrogen receptor downregulators (SERDs) such as fulvestrant (Faslodex®), RG6046, RG6047, RG6171, elacestrant (RAD-1901), SAR439859, and AZD9496; selective estrogen receptor covalent antagonists (SERCAs) such as H3B-6545; selective androgen receptor modulators (SARMs), e.g., GTX-024, darolutamide; transforming growth factors such as galunisertib, LY3200882. - beta (TGF-beta) kinase antagonists; TGF-beta inhibitors as described in WO 2019 / 103203; TGF beta receptor 1 inhibitors, such as PF-06952229; ABT-165 (DLL4 / VEGF), MM-141 (IGF-1 / ErbB3), MM-111 (Erb2 / Erb3), JNJ-64052781 (CD19 / CD3), PRS-343 (CD-137 / HER2), AFM26 (BCMA / CD16A), JNJ-61186372 (EGFR / cMET), AMG-211 (CEA / CD3), RG7802 (CEA / CD3), ERY-974 (CD3 / GPC3), vancizumab (angiopoietin / VEGF), PF-06671008 (cadherin / CD3), AFM-13 (CD16 / CD30), APVO436 (CD123 / CD3), flotetuzumab (CD123 / CD3), REGN-1979 (CD20 / CD3), MCLA-117 (CD3 / CLEC12A), MCLA-128 (HER2 / HER3), JNJ-0819, JNJ-7564 (CD3 / heme), AMG-757 (DLL3-CD3), MGD-01 3(PD-1 / LAG-3), FS-118(LAG-3 / PD-L1), MGD-019(PD-1 / CTLA-4), KN-046(PD-1 / CTLA-4), MEDI-5752(CTLA-4 / PD-1), RO-7121661(PD-1 / TIM-3), Xm Ab-20717(PD-1 / CTLA-4), AK-104(CTLA-4 / PD-1), AMG-420(BCMA / CD3), BI-836880(VEFG / ANG2), JNJ-63709178(CD123 / CD3), MGD-007(CD3 / gpA33),MGD-009(CD3 / B7H3), AGEN1223, IMCgp100(CD3 / gp100), AGEN-1423, ATOR-1015(CTLA-4 / OX40), LY-3415244(TIM-3 / PDL1), INHIBRX-105(4-1BB / PD L1), faricimab (VEGF-A / ANG-2), FAP-4-IBBL (4-1BB / FAP), XmAb-13676 (CD3 / CD20), TAK-252 (PD-1 / OX40L), TG-1801 (CD19 / CD47), XmAb-18087 (SSTR2 / CD3), catumaxomab (CD3 / EpCAM), SAR-156597 (IL4 / IL13), EMB-01 (EGFR / cMET), REGN-4018 (MUC16 / CD3), REGN-1979 (CD20 / CD3), RG-7828 (CD20 / CD3), CC-93269 (CD3 / BCMA), REGN-5458 (CD3 / BCMA), nabicizumab (DLL4 / VEGF), GRB-1302 (CD3 / Erbb2), vanucizumab (VEGF-A / ANG-2), GRB-1342 (CD38 / CD3), GEM-33 bispecific antibodies such as alpha-ketoglutarate dehydrogenase (KGDH) inhibitors, e.g., CPI-613; XPO1 inhibitors, e.g., selinexor (KPT-330); isocitrate dehydrogenase 2 (IDH2) inhibitors, e.g., enasidenib (AG-221); IDH1 inhibitors, e.g., AG-120 and AG-881 (IDH1 and IDH2), IDH -305, BAY-1436032; IDH1 gene inhibitors, such as ivosidenib; interleukin-3 receptor (IL-3R) modulators, such as SL-401; arginine deiminase stimulators, such as pegalgiminase (ADI-PEG-20); claudin-18 inhibitors, such as claudiximab; β-catenin inhibitors, such as CWP-291; chemokine receptor 2 (CCR) inhibitors, such as PF-04136309, CCX-872, BMS-813160 (CCR2 / CCR5); thymidylate synthase inhibitors, such asONX-0801; ALK / ROS1 inhibitors, e.g., lorlatinib; tankyrase inhibitors, e.g., G007-LK; triggering receptor expressed on myeloid cells 1 (TREM1; NCBI Gene ID: 54210), e.g., PY159; triggering receptor expressed on myeloid cells 2 (TREM2; NCBI Gene ID: 54209), e.g., PY314; Mdm2 p53 binding protein inhibitors, e.g., CMG-097, HDM-201; c-PIM inhibitors, e.g., PIM447; sphingosine kinase-2 (SK2) inhibitors, e.g., Yeliva® (ABC294640); DNA polymerase inhibitors, e.g., sapacitabine; cell cycle / microtubule inhibitors, e.g., eribulin mesylate; c-MET inhibitors, e.g., AMG-337, savolitinib, tivantinib (ARQ-197), capmatinib, and tepotinib. tinib, ABT-700, AG213, AMG-208, JNJ-38877618 (OMO-1), merestinib, HQP-8361; c-Met / VEGFR inhibitors, e.g., BMS-817378, TAS-115; c-Met / RON inhibitors, e.g., BMS-777607; BCR / ABL inhibitors, e.g., revastinib, asciminib, ponatinib (ICLUSIG®); MNK1 / MNK2 inhibitors, e.g., eFT-508; cytochrome P450 11B2 / cytochrome P450 17 / AKT protein kinase inhibitors, e.g., LAE-201; cytochrome P450 3A4 stimulators, such as mitotane; lysine-specific demethylase-1 (LSD1) inhibitors, such as CC-90011; CSF1R / KIT and FLT3 inhibitors, such as pexidartinib (PLX3397); Flt3 tyrosine kinase / Kit tyrosine kinase inhibitors such as quizartinib dihydrochloride, and PDGF receptor antagonists; kinase inhibitors, such as vandetanib; E-selectin antagonists, such as GMI-1271; differentiation inducers, such as tretinoin; epidermal growth factor receptor (EGFR) inhibitors, such as osimertinib (AZD-9291), cetuximab; topoisomerase inhibitors, such as adriamycin, doxorubicin, daunorubicin, dactinomycin, DaunoXome, Caelyx, eniposide, epirubicin, etoposide,Idarubicin, irinotecan, mitoxantrone, pixantrone, sobuzoxane, topotecan, irinotecan, MM-398 (liposomal irinotecan), vosaroxin and GPX-150, aldoxorubicin, AR-67, mavereltinib, AST-2818, avitinib (ACEA-0010), irofulven (MGI-114); corticosteroids such as cortisone, dexamethasone, hydrocortisone, methylprednisolone, prednisone, prednisolone; growth factor signaling kinase inhibitors; nucleoside analogues such as DF P-10917; Axl inhibitors, e.g., BGB-324 (bemcentinib), SLC-0211; Axl / Flt3 inhibitors, e.g., gilteritinib; ABBV-744, inhibitors of bromodomain and extraterminal motif (BET) proteins, including BRD2 (NCBI Gene ID: 6046), BRD3 (NCBI Gene ID: 8019), BRD4 (NCBI Gene ID: 23476), and bromodomain testis-specific protein (BRDT; NCBI Gene ID: 676), e.g., INCB-054329, INCB057643, TEN-0 10, AZD-5153, ABT-767, BMS-986158, CC-90010, GSK525762 (molybresive), NHWD-870, ODM-207, GSK-2820151, GSK-1210151A, ZBC246, ZBC260, ZEN3694, FT-1101, RG-6146, CC-90010, CC-95775, mibebrexit, BI-894999, PLX-2853, PLX-51107, CPI-0610, GS-5829; PARP inhibitors, e.g., pamiparib, fuzuloparib, tazoparib tosylate, niraparib butosylate monohydrate, rucaparib camsylate, olaparib, veliparib, ABT-767, BGB-290, bendamustine hydrochloride; PARP / tankyrase inhibitors, such as 2X-121 (e-7499); IMP-4297, SC-10914, IDX-1197, HWH-340, CK-102, simiparib; proteasome inhibitors, such as ixazomib (NINLARO®), carfilzomib (Kyprolis®), marizomib, bortezomib; glutaminase inhibitors, such as CB-839 (telaglenasto),Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES); mitochondrial complex I inhibitors, e.g., metformin, phenformin; peptide vaccine TG-01 (RAS), GALE-301, GALE-302, neripepimt-s, SurVaxM, DSP-7888, TPIV-200, PVX-410, VXL-10, Vaccines such as 0, DPX-E7, ISA-101, 6MHP, OSE-2101, Garinpepimut-S, SVN53-67 / M57-KLH, IMU-131, peptide subunit vaccine (acute lymphoblastic leukemia, University Children's Hospital Tuebingen); bacterial vector vaccines, e.g. CRS-207 / GVAX, Axalimodine phyllosvac (ADXS11-001); adenovirus vector vaccines, e.g. nadofaragene firadenovec; autologous Gp96 vaccine; dendritic cell vaccine, e.g., CVactm, stapuldencel-T, eltrapuldencel-T, rocapuldencel-T (AGS-003), DCVAC, SL-701, BSK01TM, ADXS31-142, autologous dendritic cell vaccine (metastatic melanoma, intradermal / intravenous, Universitatsklinikum Erlangen); oncolytic vaccines such as talimogene laherparepvec, pexastimodine devasilepvec, GL-ONC1, MG1-MA3, parvovirus H-1, ProstAtak, enadenocilib, MG1MA3, ASN-002 (TG-1042); therapeutic vaccines such as CVAC-301, CMP-001, CreaVax-BC, PF-06753512, VBI-1901, TG-4010, ProscaVax™; tumor cell vaccines such as Vigil® (IND-14205), Oncoquest-L vaccine. attenuated recombinant serotype 1 poliovirus vaccines, e.g., PVS-RIPO; adaggloxadocimorenin; MEDI-0457; tumor-derived autophagosome-enriched cancer vaccine, DPV-001; RNA vaccines, e.g., CV-9209, LV-305; DNA vaccines, e.g., MEDI-0457, MVI-816, INO-5401; modified vaccinia virus expressing p53, Ankara vaccine, e.g., MVA-p53; DPX-Survivac; BriaVax™; GI-6301; GI-6207; GI-4000; IO-103;Neo-antigen peptide vaccines, e.g., AGEN-2017, GEN-010, NeoVax, RG-6180, GEN-009, PGV-001 (TLR-3 agonist), GRANITE-001, NEO-PV-01; PhosphoSynVax™; Vitespen (HSPPC-96-C), NANT colorectal cancer vaccine containing aldoxorubicin, autologous tumor cell vaccine + systemic CpG-B + IFN-alpha (cancer), IO-120 + IO-103 (PD-L1 / PD-L2 vaccine), HB-201, HB-202, HB-301, TheraT-based vaccines peptide vaccines targeting heat shock proteins such as cutin; TLR-3 agonists / interferon inducers such as polyICLC (NSC-301463); STAT-3 inhibitors such as napabvacacin (BBI-608); ATPase p97 inhibitors such as CB-5083; Smoothened (SMO) receptor inhibitors such as Odomzo® (sonidegib, formerly LDE-225), LEQ506, vismodegib (GDC-0449), BMS-833923, glasdegib (PF-04449913), LY2940680, and itraconazole;Interferon alpha ligand modulators, such as interferon alpha-2b, interferon alpha-2a biosimilars (Biogenomics), PEG interferon alpha-2b (AOP-2014, P-1101, PEG IFN alpha-2b), multiferon (Alpha Nativ, Viragen), interferon alpha 1b, Roferon-A (Camferon, Ro-25-3036), interferon alpha-2a post-development (Biosidus) (Inmutag, Inter 2A), interferon alpha-2b post-development (Biosidus-Bioferon, Citoferon, Ganapar, Beijing Kawin Technology-Kaferon), Alphaferon, PEGylated interferon alpha-1b, pegylated interferon alpha-2b post-development formulation (Amega), recombinant human interferon alpha-1b, recombinant human interferon alpha-2a, recombinant human interferon alpha-2b, veltuzumab-IFN alpha 2b conjugate, Dynavax (SD-101), and interferon alpha-n1 (Humoferon, SM-10500, Sumiferon); interferon gamma ligand modulators, e.g., interferon gamma (OH-6000, Ogamma100); tertomotide (GV-1001, HR-2802, Riavax) and imetelstat (GRN- 163, JNJ-63935937); DNA methyltransferase inhibitors such as temozolomide (CCRG-81045), decitabine, oral decitabine and cedazuridine (ASTX727), guadecitabine (S-110, SGI-110), KRX-0402, RX-3117, RRx-001, and azacitidine (CC-486); DNA gyrase inhibitors such as pixantrone and sobuzoxane; DNA gyrase inhibitors / topoisomerase II inhibitors such as amrubicin; Bcl-2 family protein inhibitors such as ABT-263, venetoclax (ABT-199), obatoclax mesylate, pelcitoclax, ABT-737, RG7601, and AT-101;Bcl-2 / Bcl-XL inhibitors, e.g., Navitoclax (ABT-263; RG-7433); Notch inhibitors, e.g., LY3039478 (Crenigacestat), Tarexuzumab (anti-Notch2 / 3), BMS-906024; hyaluronidase stimulators, e.g., PEGPH-20; Erbb2 tyrosine kinase receptor inhibitors / hyaluronidase stimulators, e.g., Herceptin Hylecta; Wnt pathway inhibitors, e.g., SM-04755, PRI-724, WNT-974; gamma secretase inhibitors, For example, PF-03084014, MK-0752, RO-4929097; Grb-2 (growth factor receptor-bound protein-2) inhibitors, for example, BP1001; TRAIL pathway inducing compounds, for example, ONC201, ABBV-621; TRAIL modulators, for example, SCB-313; focal adhesion kinase inhibitors, for example, VS-4718, defactinib, GSK2256098; hedgehog inhibitors, for example, salidegib, sonidegib (LDE225), glasdegib; Aurora kinase inhibitors, for example, alisertib ( MLN-8237), and AZD-2811, AMG-900, barasertib, ENMD-2076; HSPB1 modulators (heat shock protein 27, HSP27), such as brivudine, apatorsen; ATR inhibitors, such as BAY-937, AZD6738, AZD6783, VX-803, VX-970 (berzosertib), and VX-970; Hsp90 inhibitors, such as AUY922, onarespib (AT13387), SNX-2112, SNX5422; DS-3032b, RG7775, AMG- mouse double minute chromosome (mdm2) oncogene inhibitors such as 232, HDM201, and idazanutulin (RG7388); CD137 agonists such as urelumab, utomilumab (PF-05082566), AGEN2373, ADG-106, BT-7480, and QL1806; STING agonists such as ADU-S100 (MIW-815), SB-11285, MK-1454, SR-8291, AdVCA0848, GSK-532, SYN-STING, MSA-1, SR-8291, and GSK3745417;FGFR inhibitors such as FGF-401, INCB-054828, BAY-1163877, AZD4547, JNJ-42756493, LY2874455, Debio-1347; fatty acid synthase (FASN) inhibitors such as TVB-2640; CD44 binders such as A6; protein phosphatase 2A (PP2A) inhibitors such as LB-100; CYP17 inhibitors such as ceviteronel (VT-464), ASN-001, ODM-204, CFG920, abiraterone acetate; RXR agonists such as IRX4204; hedgehog / smoothened (hh / Smo) antagonists such as taladegib, pachidegib, vismodegib; complement C3 modulators such as Imprime PGG; IL-15 agonists, e.g., ALT-803, NKTR-255, interleukin-15 / Fc fusion protein, AM-0015, NIZ-985, and hetIL-15; EZH2 (enhancer of zeste homolog 2) inhibitors, e.g., tazemetostat, CPI-1205, GSK-2816126, PF-06821497; pelareorep, CG-0070, MV-NIS therapy, HSV-1716, DS-1647, VCN-01, ONCOS-102, TBI-1401, tasadenoturev (DNX-2401), vocimagene Oncolytic viruses such as amiretrorepvec, RP-1, CVA21, Celyvir, LOAd-703, OBP-301, IMLYGIC®; DOT1L (histone methyltransferase) inhibitors such as pinometostat (EPZ-5676); toxins, e.g., cholera toxin, ricin, Pseudomonas exotoxin, Bordetella pertussis adenylate cyclase toxin, diphtheria toxin, and caspase activators; DNA plasmids, e.g., BC-819; PLK inhibitors of PLK1, 2, and 3, e.g., volasertib (PLK1); WEE1 inhibitors, e.g., AZD-1775 (adavosertib); Rho kinase (ROCK) inhibitors, e.g., AT13148, KD025; inhibitor of apoptosis protein (IAP) inhibitors, e.g., ASTX660, debio-1143, birinapant, APG-1387, LCL-161;RNA polymerase inhibitors, such as lurbinectedin (PM-1183), CX-5461; PM-184, BAL-101553 (risabumbulin), and OXI-4503, tubulin inhibitors such as fluorapasin (AC-0001), plinabulin, and vinflunine; Toll-like receptor 4 (TLR-4) agonists, such as G100, GSK1795091, and PEPA-10; elongation factor 1 alpha 2 inhibitors, such as plitidepsin; elongation factor 2 inhibitors / interleukin-2 ligand / NAD ADP-ribosyltransferase stimulators, such as denileukin diftitox; CD95 inhibitors, such as APG-101, APO-010, asnercept; WT1 inhibitors, such as splicing factor 3B subunit 1 (SF3B1) inhibitors, such as DSP-7888, H3B-8800; retinoid Z receptor gamma (RORγ) agonists, such as LYC-55716; and microbiome modulating agents, such as SER-401, EDP-1503, MRx-0518.

[0077] In various embodiments, the agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with one or more additional therapeutic agents, including inhibitors or antagonists of the following: myeloid cell leukemia sequence 1 (MCL1) apoptosis regulator (NCBI Gene ID: 4170); mitogen-activated protein kinase 1 (MAP4K1) (also referred to as hematopoietic progenitor kinase 1 (HPK1), NCBI Gene ID: 11184); diacylglycerol kinase alpha (DGKA, DAGK, DAGK1, or DGK-alpha; NCBI Gene ID: :1606); ecto-5'-nucleotidase (NT5E or CD73; NCBI Gene ID:4907); ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1 or CD39; NCBI Gene ID:593); transforming growth factor beta 1 (TGFB1 or TGFβ; NCBI Gene ID:7040); heme oxygenase 1 (HMOX1, HO-1, or HO1; NCBI Gene ID:3162); heme oxygenase 2 (HMOX2, HO-2, or HO2; NCBI Gene ID:3163 ); vascular endothelial growth factor A (VEGFA or VEGF; NCBI Gene ID: 7422); erb-b2 receptor tyrosine kinase 2 (ERBB2, HER2, HER2 / neu, or CD340; NCBI Gene ID: 2064), epidermal growth factor receptor (EGFR, ERBB, ERBB1, or HER1; NCBI Gene ID: 1956); ALK receptor tyrosine kinase (ALK, CD246; NCBI Gene ID: 238); poly(ADP-ribose) polymerase 1 (PARP1; NCBI Gene ID: 142); poly(ADP-ribose) polymerase 2 (PARP2; NCBI Gene ID: 10038); TCDD-inducible poly(ADP-ribose) polymerase (TIPARP, PARP7; NCBI Gene ID: 25976); cyclin-dependent kinase 4 (CDK4; NCBI Gene ID: 1019); cyclin-dependent kinase 6 (CDK6; NCBI Gene ID: 1021); TNF receptor superfamily member 14 (TNFRSF14, HVEM, CD270; NCBI Gene ID: 8764);T cell immunoreceptor with Ig and ITIM domains (TIGIT; NCBI Gene ID: 201633); X-linked inhibitor of apoptosis (XIAP, BIRC4, IAP-3; NCBI Gene ID: 331); baculovirus IAP repeat-containing 2 (BIRC2, cIAP1; NCBI Gene ID: 329); baculovirus IAP repeat-containing 3 (BIRC3, cIAP2; NCBI Gene ID: 330); baculovirus IAP repeat-containing 5 (BIRC5, survivin; NCBI Gene ID: 332); CC motif chemokine receptor 2 (CCR2, CD192; NCBI gene ID: 729230); CC motif chemokine receptor 5 (CCR5, CD195; NCBI gene ID: 1234); CC motif chemokine receptor 8 (CCR8, CDw198; NCBI gene ID: 1237); CXC motif chemokine receptor 2 (CXCR2, CD182; NCBI gene ID: 3579); CXC motif chemokine receptor 3 (CXCR3, CD182, CD183; NCBI gene ID: 2833); CXC motif chemokine receptor 4 (CXCR4, CD184; NCBI Gene ID: 7852); arginase (ARG1 (NCBI Gene ID: 383), ARG2 (NCBI Gene ID: 384)), carbonic anhydrase (CA1 (NCBI Gene ID: 759), CA2 (NCBI Gene ID: 760), CA3 (NCBI Gene ID: 761), CA4 (NCBI Gene ID: 762), CA5A (NCBI Gene ID: 763), CA5B (NCBI Gene ID: 11238), CA6 (NCBI Gene ID: 765), CA7 (NCBI Gene ID: 766) ), CA8 (NCBI Gene ID: 767), CA9 (NCBI Gene ID: 768), CA10 (NCBI Gene ID: 56934), CA11 (NCBI Gene ID: 770), CA12 (NCBI Gene ID: 771), CA13 (NCBI Gene ID: 377677), CA14 (NCBI Gene ID: 23632)), prostaglandin endoperoxide synthase 1 (PTGS1, COX-1; NCBI Gene ID: 5742), prostaglandin endoperoxide synthase 2 (PTGS2, COX-2;NCBI Gene ID: 5743), secretory phospholipase A2, prostaglandin E synthase (PTGES, PGES; Gene ID: 9536), arachidonate 5-lipoxygenase (ALOX5, 5-LOX; NCBI Gene ID: 240), and / or soluble epoxide hydrolase 2 (EPHX2, SEH; NCBI Gene ID: 2053); secretory phospholipase A2 (e.g., PLA2G1B (NCBI Gene ID: 5319) ;PLA2G7(NCBI Gene ID:7941), PLA2G3(NCBI Gene ID:50487), PLA2G2A(NCBI Gene ID:5320);PLA2G4A(NCBI Gene ID:5321);PLA2G12A(NCBI Gene ID:81579);PLA2G12B(NCBI Gene ID:84647);PLA2G10(NCBI Gene ID:8399);PLA2G5(NCBI Gene ID:5322);PLA2G 2D (NCBI Gene ID: 26279); PLA2G15 (NCBI Gene ID: 23659)); indoleamine-2,3-dioxygenase 1 (IDO1; NCBI Gene ID: 3620); indoleamine-2,3-dioxygenase 2 (IDO2; NCBI Gene ID: 169355); hypoxia-inducible factor 1 subunit alpha (HIF1A; NCBI Gene ID: 3091); angiopoietin 1 (ANGPT1; NCBI Gene ID: 23659) NCBI Gene ID: 284); endothelial TEK tyrosine kinase (TIE-2, TEK, CD202B; NCBI Gene ID: 7010); Janus kinase 1 (JAK1; NCBI Gene ID: 3716); catenin beta 1 (CTNNB1; NCBI Gene ID: 1499); histone deacetylase 9 (HDAC9; NCBI Gene ID: 9734), and / or 5'-3' exoribonuclease 1 (XRN1; NCBI Gene ID: 54464).

[0078] In various embodiments, the agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with agonists of fms-related receptor tyrosine kinase 3 (FLT3; FLK2; STK1; CD135; FLK-2; NCBI gene ID: 2322). Examples of FLT3 agonists include, but are not limited to, CDX-301 and GS-3583. GS-3583 is described, for example, in WO 2020 / 263830, which is incorporated herein by reference in its entirety for all purposes.

[0079] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-CD19 agent or antibody. Examples of anti-CD19 agents or antibodies that may be co-administered include, but are not limited to, blinatumomab, tafasitamab, XmAb5574 (Xencor), AFM-11, inebilizumab, loncastuximab, MEDI 551 (Cellective Therapeutics); and MDX-1342 (Medarex).

[0080] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-CD20 agent or antibody. Examples of anti-CD20 agents or antibodies that may be co-administered include, but are not limited to, IGN-002, PF-05280586; rituximab (Rituxan / Biogen Idec), ofatumumab (Arzerra / Genmab), obinutuzumab (Gazyva / Roche Glycart Biotech), alemtuzumab, veltuzumab, ocrelizumab (Ocrevus / Biogen Idec; Genentech), ocaratuzumab and ublituximab, and LFB-R603 (LFB Biotech.; rEVO Biologics).

[0081] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-CD22 agent or antibody. Examples of anti-CD22 agents or antibodies that may be co-administered include, but are not limited to, epratuzumab, AMG-412, IMMU-103 (Immunomedics).

[0082] In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-CD30 agent or antibody. Examples of anti-CD30 agents or antibodies that may be co-administered include, but are not limited to, brentuximab vedotin (Seattle Genetics).

[0083] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-CD33 agent or antibody. Examples of anti-CD33 agents or antibodies that may be co-administered include, but are not limited to, gemtuzumab, lintuzumab, vadastuximab, CIK-CAR.CD33;CD33CART, AMG-330 (CD33 / CD3), AMG-673 (CD33 / CD3), and GEM-333 (CD3 / CD33), and IMGN-779.

[0084] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-CD37 agent or antibody. Examples of anti-CD37 agents or antibodies that may be co-administered include, but are not limited to, BI836826 (Boehringer Ingelheim), Otlertuzumab, and TRU-016 (Trubion Pharmaceuticals).

[0085] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-CD38 agent or antibody. Exemplary anti-CD38 agents or antibodies that may be co-administered include, but are not limited to, CD38, such as T-007, UCART-38; Darzalex (Genmab), daratumumab, JNJ-54767414 (Darzalex / Genmab), isatuximab, SAR650984 (ImmunoGen), MOR202, MOR03087 (MorphoSys), TAK-079; and anti-CD38-attenukines, such as TAK573.

[0086] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-CD52 agent or antibody. Examples of anti-CD52 agents or antibodies that may be co-administered include, but are not limited to, anti-CD52 antibodies, such as alemtuzumab (Campath / University of Cambridge).

[0087] In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-CD98 (4F2, FRP-1) agent or antibody. Examples of anti-CD98 agents or antibodies that may be co-administered include, but are not limited to, IGN523 (Igenica).

[0088] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-CD157 (BST-1) agent or antibody. Examples of anti-CD157 agents or antibodies that may be co-administered include, but are not limited to, OBT357, MEN1112 (Menarini; Oxford BioTherapeutics).

[0089] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-DKK-1 agent or antibody. Examples of anti-DKK-1 agents or antibodies that may be co-administered include, but are not limited to, BHQ880 (MorphoSys; Novartis) and DKN-01, LY-2812176 (Eli Lilly).

[0090] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-GRP78 (BiP) agent or antibody. Examples of anti-GRP78 agents or antibodies that may be co-administered include, but are not limited to, PAT-SM6 (OncoMab GmbH).

[0091] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-NOTCH1 agent or antibody. Examples of anti-NOTCH1 agents or antibodies that may be co-administered include, but are not limited to, Brontictuzumab, OMP-52M51 (OncoMed Pharmaceuticals).

[0092] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-ROR1 agent or antibody. Examples of anti-ROR1 agents or antibodies that may be co-administered include, but are not limited to, mapatuzumab, TRM1, HGS-1012 (Cambridge Antibody Technology).

[0093] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-SLAMF7 (CS1, CD319) agent or antibody. Examples of anti-SLAMF7 agents or antibodies that may be co-administered include, but are not limited to, elotuzumab, HuLuc63, BMS-901608 (Empliciti / PDL BioPharma), mogamulizumab (KW-0761).

[0094] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with anti-TNFRSF10A (DR4; APO2; CD261; TRAILR1; TRAILR-1) agents or antibodies. Examples of anti-TNFRSF10A agents or antibodies that may be co-administered include, but are not limited to, mapatuzumab, TRM1, HGS-1012 (Cambridge Antibody Technology).

[0095] In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-transferrin receptor (TFRC; CD71) agent or antibody. Examples of anti-transferrin receptor agents or antibodies that may be co-administered include, but are not limited to, E2.3 / A27.15 (University of Arizona).

[0096] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-EPHA3 agent or antibody. Examples of anti-EPHA3 agents or antibodies that may be co-administered include, but are not limited to, Ifabotuzumab, KB004 (Ludwig Institute for Cancer Research).

[0097] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-CCR4 agent or antibody. Examples of anti-CCR4 agents or antibodies that may be co-administered include, but are not limited to, mogamulizumab, KW-0761 (Poteligeo / Kyowa Hakko Kirin Co.).

[0098] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-CXCR4 agent or antibody. Examples of anti-CXCR4 agents or antibodies that may be co-administered include, but are not limited to, BMS-936564, MDX-1338 (Medarex), and PF-06747143 (Pfizer).

[0099] In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-BAFF agent or antibody. Examples of anti-BAFF agents or antibodies that may be co-administered include, but are not limited to, tabalumab, LY2127399 (Eli Lilly).

[0100] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-BAFF receptor (BAFF-R) agent or antibody. Examples of anti-BAFF-R agents or antibodies that may be co-administered include, but are not limited to, VAY736 (MorphoSys; Novartis).

[0101] In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-RANKL agent or antibody. Examples of anti-RANKL agents or antibodies that may be co-administered include, but are not limited to, denosumab, AMG-162 (Prolia; Ranmark; Xgeva / Amgen).

[0102] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-IL-6 agent or antibody. Examples of anti-IL-6 agents or antibodies that may be co-administered include, but are not limited to, siltuximab, CNTO-328 (Sylvant / Centocor).

[0103] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-IL-6 receptor (IL-6R) agent or antibody. Examples of anti-IL-6R agents or antibodies that may be co-administered include, but are not limited to, tocilizumab, R-1569 (Actemra / Chugai Pharmaceutical; Osaka University), or AS-101 (CB-06-02, IVX-Q-101).

[0104] In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-IL3RA (CD123) agent or antibody. Examples of anti-IL3RA (CD123) agents or antibodies that may be co-administered include, but are not limited to, tagraxofusp, talaxuzumab (JNJ-56022473; CSL362 (CSL)), pivekimab suniline (IMGN632), MB-102 (Mustang Bio), CSL360 (CSL); bibecotamab (XmAb14045; Xencor); KHK2823 (Kyowa Hakko Kirin Co.); MGD-024 (CD123 / CD3; Macrogenics), APVO436 (CD123 / CD3); flotetuzumab (CD123 / CD3); JNJ-63709178 (CD123, CD3); and XmAb-14045 (CD123 / CD3) (Xencor).

[0105] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-IL2RA (CD25) agent or antibody. Examples of anti-IL2RA agents or antibodies that may be co-administered include, but are not limited to, basiliximab, SDZ-CHI-621 (Simulect / Novartis), and daclizumab.

[0106] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-IGF-1R (CD221) agent or antibody. Examples of anti-IGF-1R agents or antibodies that may be co-administered include, but are not limited to, ganitumab, AMG-479 (Amgen); ganitumab, AMG-479 (Amgen), dalotuzumab, MK-0646 (Pierre Fabre), and AVE1642 (ImmunoGen).

[0107] In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-GM-CSF (CSF2) agent or antibody. An example of an anti-GM-CSF agent or antibody that may be co-administered includes, but is not limited to, lenzilumab (aka KB003; KaloBios Pharmaceuticals).

[0108] In various embodiments, the agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-HGF agent or antibody. Examples of anti-HGF agents or antibodies that may be co-administered include, but are not limited to, ficlatuzumab, AV-299 (AVEO Pharmaceuticals).

[0109] In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-CD44 agent or antibody. Examples of anti-CD44 agents or antibodies that may be co-administered include, but are not limited to, RG7356, RO5429083 (Chugai Biopharmaceuticals; Roche).

[0110] In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-VLA-4 (CD49d) agent or antibody. Examples of anti-VLA-4 agents or antibodies that may be co-administered include, but are not limited to, natalizumab, BG-0002-E (Tysabri / Elan Corporation).

[0111] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-ICAM-1 (CD54) agent or antibody. Examples of anti-ICAM-1 agents or antibodies that may be co-administered include, but are not limited to, BI-505 (BioInvent International).

[0112] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-VEGF-A agent or antibody. Examples of anti-VEGF-A agents or antibodies that may be co-administered include, but are not limited to, bevacizumab (Avastin / Genentech; Hackensack University Medical Center).

[0113] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with anti-endosialin (CD248, TEM1) agents or antibodies. Examples of anti-endosialin agents or antibodies that may be co-administered include, but are not limited to, ontecizumab, MORAB-004 (Ludwig Institute for Cancer Research; Morphotek).

[0114] In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-CD79 agent or antibody. Examples of anti-CD79 agents or antibodies that may be co-administered include, but are not limited to, polatuzumab, DCDS4501A, RG7596 (Genentech).

[0115] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-isocitrate dehydrogenase (IDH) agent or antibody. Examples of anti-IDH agents or antibodies that may be co-administered include, but are not limited to, the IDH1 inhibitor ivosidenib (Tibsovo; Agios) and the IDH 2 inhibitor enasidenib (Idhifa; Celgene / Agios).

[0116] In various embodiments, an agent that inhibits the binding between CD47 and SIRPα (e.g., magrolimab) and an anti-Trop-2 ADC (e.g., sacituzumab govitecan) described herein is further combined with an anti-major histocompatibility complex, class I, G (HLA-G; NCBI gene ID: 3135) antibody, such as TTX-080.

[0117] In various embodiments, an agent that inhibits the binding between CD47 and SIRPα (e.g., magrolimab) and an anti-Trop-2 ADC (e.g., sacituzumab govitecan) described herein is further combined with an anti-Leukocyte Immunoglobulin-Like Receptor B2 (LILRB2, also known as CD85D, ILT4; NCBI Gene ID: 10288) antibody, such as JTX-8064 or MK-4830.

[0118] Agonists or activators of members of the TNF Receptor Superfamily (TNFRSF) In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein may also inhibit the binding of one or more TNF receptor superfamily (TNFRSF) members, such as agonists of TNFRSF1A (NCBI Gene ID: 7132), TNFRSF1B (NCBI Gene ID: 7133), TNFRSF4 (OX40, CD134; NCBI Gene ID; 7293), TNFRSF5 (CD40; NCBI Gene ID; 958), TNFRSF6 (FAS, NCBI Gene ID; 355), TNFRSF7 ( CD27, NCBI gene ID; 939), TNFRSF8 (CD30, NCBI gene ID; 943), TNFRSF9 (4-1BB, CD137, NCBI gene ID; 3604), TNFRSF10A (CD261, DR4, TRAILR1, NCBI gene ID; 8797), TNFRSF10B (CD262, DR5, TRAILR2, NCBI gene ID; 8795), TNFRSF10C (CD263, TRAILR3, NCBI gene ID; 8794), T NFRSF10D (CD264, TRAILR4, NCBI gene ID; 8793), TNFRSF11A (CD265, RANK, NCBI gene ID; 8792), TNFRSF11B (NCBI gene ID; 4982), TNFRSF12A (CD266, NCBI gene ID; 51330), TNFRSF13B (CD267, NCBI gene ID; 23495), TNFRSF13C (CD268, NCBI gene ID; 115650), TNFRSF16 (NG and / or one or more agonists of TNFRSF17 (BCMA, CD269, NCBI Gene ID; 608), TNFRSF18 (GITR, CD357, NCBI Gene ID; 8784), TNFRSF19 (NCBI Gene ID; 55504), TNFRSF21 (CD358, DR6, NCBI Gene ID; 27242), and TNFRSF25 (DR3, NCBI Gene ID; 8718).

[0119] Exemplary anti-TNFRSF4 (OX40) antibodies that may be co-administered include, but are not limited to, MEDI6469, MEDI6383, MEDI0562 (tabolixizumab), MOXR0916, PF-04518600, RG-7888, GSK-3174998, INCAGN1949, BMS-986178, GBR-8383, ABBV-368, and antibodies described in WO2016179517, WO2017096179, WO2017096182, WO2017096281, and WO2018089628, each of which is incorporated by reference in its entirety.

[0120] Exemplary anti-TNF receptor superfamily member 10b (TNFRSF10B, DR5, TRAILR2) antibodies that may be co-administered include, but are not limited to, DS-8273, CTB-006, INBRX-109, and GEN-1029.

[0121] Anti-TNFRSF5 (CD40) antibodies that may be co-administered include, but are not limited to, celicrelumab (RO7009789), mitazalimab (also known as banalimab, ADC-1013, JNJ-64457107), RG7876, SEA-CD40, APX-005M, and ABBV-428, ABBV-927, and JNJ-64457107.

[0122] Examples of anti-TNFRSF7 (CD27) agents that may be co-administered include, but are not limited to, valilumab (CDX-1127).

[0123] Examples of anti-TNFRSF9 (4-1BB, CD137) antibodies that may be co-administered include, but are not limited to, urelumab, utomilumab (PF-05082566), AGEN2373, and ADG-106, BT-7480, and QL1806.

[0124] Examples of anti-TNFRSF17 (BCMA) agents that may be co-administered include, but are not limited to, GSK-2857916.

[0125] Examples of anti-TNFRSF18 (GITR) antibodies that may be co-administered include, but are not limited to, MEDI1873, FPA-154, INCAGN-1876, TRX-518, BMS-986156, MK-1248, GWN-323, and those described in WO 2017096179, WO 2017096276, WO 2017096189, and WO 2018089628. In some embodiments, an antibody or fragment thereof that simultaneously targets TNFRSF4 (OX40) and TNFRSF18 (GITR) is co-administered. Such antibodies are described, for example, in WO 2017096179 and WO 2018089628, each of which is incorporated herein by reference in its entirety.

[0126] Exemplary anti-TRAILR1, anti-TRAILR2, anti-TRAILR3, anti-TRAILR4 antibodies that may be co-administered include, but are not limited to, ABBV-621.

[0127] Examples of bispecific antibodies targeting TNFRSF family members that can be co-administered include, but are not limited to, PRS-343 (CD-137 / HER2), AFM26 (BCMA / CD16A), AFM-13 (CD16 / CD30), REGN-1979 (CD20 / CD3), AMG-420 (BCMA / CD3), INHIBRX-105 (4-1BB / PDL1), FAP-4-IBBL (4-1BB / FAP), XmAb-13676 (CD3 / CD20), RG-7828 (CD20 / CD3), CC-93269 (CD3 / BCMA), REGN-5458 (CD3 / BCMA), and IMM-0306 (CD47 / CD20), and AMG-424 (CD38.CD3).

[0128] Examples of PVR-related immunoglobulin domain-containing (PVRIG, CD112R) inhibitors that may be co-administered include, but are not limited to, COM-701.

[0129] Examples of inhibitors of T cell immunoreceptor with Ig and ITIM domains (TIGIT; NCBI Gene ID: 201633) that may be co-administered include, but are not limited to, BMS-986207, RG-6058, AGEN-1307, and COM-902, etigilimab, tiragolumab (also known as MTIG-7192A; RG-6058; RO 7092284), AGEN1777, IBI-939, AB154, MG1131, and EOS884448 (EOS-448).

[0130] Examples of inhibitors of Hepatitis A Virus Cellular Receptor 2 (HAVCR2, TIMD3, TIM-3) that may be co-administered include, but are not limited to, covolimab (TSR-022), LY-3321367, sabatolimab (MBG-453), INCAGN-2390, RO-7121661 (PD-1 / TIM-3), LY-3415244 (TIM-3 / PDL1), and RG7769 (PD-1 / TIM-3).

[0131] Examples of inhibitors of lymphocyte activation 3 (LAG-3, CD223) that may be co-administered include, but are not limited to, leratolimab (ONO-4482), LAG-525, MK-4280, REGN-3767, INCAGN2385, TSR-033, MGD-013 (PD-1 / LAG-3), and FS-118 (LAG-3 / PD-L1).

[0132] Examples of anti-killer cell immunoglobulin-like receptor, three Ig domains, and long cytoplasmic tail 1 (KIR3DL1; KIR; NCBI Gene ID: 3811) monoclonal antibodies include lirilumab (IPH-2102), IPH-4102, etc.

[0133] An example of an anti-NKG2a antibody that may be co-administered includes, but is not limited to, monalizumab.

[0134] Examples of anti-V-set immunoregulatory receptor (VSIR, B7H5, VISTA) antibodies that may be co-administered include, but are not limited to, HMBD-002, and CA-170 (PD-L1 / VISTA).

[0135] Examples of anti-CD70 antibodies that may be co-administered include, but are not limited to, AMG-172.

[0136] Examples of anti-ICOS antibodies that may be co-administered include, but are not limited to, JTX-2011, GSK3359609.

[0137] Examples of ICOS agonists that may be co-administered include, but are not limited to, ICOS-L.COMP (Gariepy, et al. 106th Annu Meet Am Assoc Immunologists (AAI) (May 9-13, San Diego) 2019, Abst 71.5).

[0138] Immune checkpoint inhibitors In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with one or more immune checkpoint inhibitors. In some embodiments, the one or more immune checkpoint inhibitors are proteinaceous (e.g., antibodies or fragments thereof, or antibody mimetics) inhibitors of PD-L1 (CD274), PD-1 (PDCD1), or CTLA4. In some embodiments, the one or more immune checkpoint inhibitors include small organic molecule inhibitors of PD-L1 (CD274), PD-1 (PDCD1), or CTLA4.

[0139] Examples of CTLA4 inhibitors that may be co-administered include, but are not limited to, ipilimumab, tremelimumab, BMS-986218, AGEN1181, AGEN1884, BMS-986249, MK-1308, REGN-4659, ADU-1604, CS-1002, BCD-145, APL-509, JS-007, BA-3071, ONC-392, AGEN-2041, JHL-1155, KN-044, CG-0161, ATOR- 1144, PBI-5D3H5, BPI-002, HBM-4003, and the multispecific inhibitors FPT-155 (CTLA4 / PD-L1 / CD28), PF-06936308 (PD-1 / CTLA4), MGD-019 (PD-1 / CTLA4), KN-046 (PD-1 / CTLA4), MEDI-5752 (CTLA4 / PD-1), XmAb-20717 (PD-1 / CTLA4), and AK-104 (CTLA4 / PD-1).

[0140] Examples of PD-L1 (CD274) or PD-1 (PDCD1) inhibitors / antibodies that may be co-administered include zimberelimab, pembrolizumab (KEYTRUDA®, MK-3477), nivolumab (OPDIVO®, BMS-936558, MDX-1106), cemiplimab, pidilizumab, spartalizumab (PDR-001), atezolizumab (RG-7446; TECENTRIQ, MPDL3280A), durvalumab (MEDI-4736), avelumab (MSB0010718C), tislelizumab (BGB -A317), toripalimab (JS-001), genolimuzumab (CBT-501), camrelizumab (SHR-1210), dostallimab (TSR-042), sintilimab (IBI-308), tislelizumab (BGB-A317), cemiplimab (REGN-2810), lambrolizumab (CAS Registry Number 1374853-91-4), AMG-404, AMP-224, MEDI0680 (AMP-514), BMS-936559, CK-301, PF-06801591, GEN-1046 (PD-L1 / 4-1BB), GLS-01 0(WBP-3055), AK-103(HX-008), AK-105, CS-1003, HLX-10, MGA-012, BI-754091, AGEN-2034, JNJ-63723283, LZM-009, BCD-100, LY-3300054, SHR-12 01, Sym-021, ABBV-181, PD1-PIK, BAT-1306, CX-072, CBT-502, MSB-2311, JTX-4014, BGB-A333, SHR-1316, CS-1001(WBP-3155, KN-035, HLX-20, KL-A1 67, STI-A1014, STI-A1015 (IMC-001), BCD-135, FAZ-053, TQB-2450, MDX1105-01, GS-4224, GS-4416, INCB086550, MAX10181, and multispecific inhibitors FPT-155 (CTLA4 / PD-L1 / CD28), PF-06936308 (PD-1 / CTLA4), MGD-013 (PD-1 / LAG-3), RO-7247669 (PD-1 / LAG-3), FS-118 (LAG-3 / PD-L1) MGD-019 (PD-1 / CTLA4),KN-046(PD-1 / CTLA4), MEDI-5752(CTLA4 / PD-1), RO-7121661(PD-1 / TIM-3), XmAb-20717(PD-1 / CTLA4), AK-104(CTLA4 / PD-1), M7824(PD-L1 / TGFβ-EC domain), CA-170 (PD-L1 / VISTA), CDX-527 (CD27 / PD-L1), LY-3415244 (TIM-3 / PDL1), RG7769 (PD-1 / TIM-3) and INBRX-105 (4-1BB / PDL1), GNS-1480 (PD-L1 / EGFR), SCH-900475, PF-06801591, AGEN-2034, AK-105, PD1-PIK, BAT-1306, BMS-936559, CK-301, MEDI-0680, PDR001+Tafinlar®+Mekinist®, and those described in, for example, WO 2018195321, WO 2020014643, WO 2019160882, and WO 2018195321, but are not limited thereto.

[0141] In various embodiments, the anti-CD47 agents described herein are combined with inhibitors of MCL1 apoptosis regulators, BCL2 family members (MCL1, TM; EAT; MCL1L; MCL1S; Mcl-1; BCL2L3; MCL1-ES; bcl2-L-3; mcl1 / EAT; NCBI gene ID: 4170). Examples of MCL1 inhibitors include AMG-176, AMG-397, S-64315 and AZD-5991, 483-LM, A-1210477, UMI-77, JKY-5-037, and those described in WO 2018183418, WO 2016033486, and WO 2017147410.

[0142] Toll-like receptor (TLR) agonists In various embodiments, the anti-CD47 agents or anti-SIRPα agents described herein are combined with an agonist of a Toll-like receptor (TLR), such as an agonist of TLR1 (NCBI Gene ID: 7096), TLR2 (NCBI Gene ID: 7097), TLR3 (NCBI Gene ID: 7098), TLR4 (NCBI Gene ID: 7099), TLR5 (NCBI Gene ID: 7100), TLR6 (NCBI Gene ID: 10333), TLR7 (NCBI Gene ID: 51284), TLR8 (NCBI Gene ID: 51311), TLR9 (NCBI Gene ID: 54106), and / or TLR10 (NCBI Gene ID: 81793).Exemplary TLR7 agonists that may be co-administered include, but are not limited to, DS-0509, GS-9620, LHC-165, TMX-101 (imiquimod), GSK-2245035, resiquimod, DSR-6434, DSP-3025, IMO-4200, MCT-465, MEDI-9197, 3M-051, SB-9922, 3M-052, Limtop, TMX-30X, TMX-202, RG-7863, RG-7795, and the TLR7 agonists described in U.S. Patent Application Publication Nos. 20100143301 (Gilead Sciences), 20110098248 (Gilead Sciences), and 20090047249 (Gilead Sciences). Sciences), 20140045849 (Janssen), 20140073642 (Janssen), WO 2014 / 056953 (Janssen), WO 2014 / 076221 (Janssen), WO 2014 / 128189 (Janssen), U.S. Patent Application Publication No. 20140350031 (Janssen), WO 2014 / 023813 (Janssen), U.S. Patent Application Publication No. 20080234251 (Array Biopharma), U.S. Patent Application Publication No. 20080306050 (Array Biopharma), U.S. Patent Application Publication No. 20100029585 (Ventirx Pharma), U.S. Patent Application Publication No. 20110092485 (Ventirx Examples of TLR7 / TLR8 agonists that may be co-administered include those disclosed in Ventirx Pharma, No. 20110118235 (Ventirx Pharma), No. 20120082658 (Ventirx Pharma), No. 20120219615 (Ventirx Pharma), No. 20140066432 (Ventirx Pharma), No. 20140088085 (Ventirx Pharma), No. 20140275167 (Novira Therapeutics), and No. 20130251673 (Novira Therapeutics). A TLR7 / TLR8 agonist that may be co-administered is NKTR-262.Examples of TLR8 agonists that may be co-administered include, but are not limited to, E-6887, IMO-4200, IMO-8400, IMO-9200, MCT-465, MEDI-9197, motolimod, resiquimod, GS-9688, VTX-1463, VTX-763, 3M-051, 3M-052, and those described in U.S. Patent Application Publication No. 20140045849 (Janssen), ... No. 140073642 (Janssen), WO 2014 / 056953 (Janssen), WO 2014 / 076221 (Janssen), WO 2014 / 128189 (Janssen), U.S. Patent Application Publication No. 20140350031 (Janssen), WO 2014 / 023813 (Janssen), U.S. Patent Application Publication No. 20080234251 (Array No. 20100029585 (Ventirx Pharma), U.S. Patent Application Publication No. 20110092485 (Ventirx Pharma), U.S. Patent Application Publication No. 20110118235 (Ventirx Pharma), U.S. Patent Application Publication No. 20120082658 (Ventirx Pharma), U.S. Patent Application Publication No. 20120219615 (Ventirx Pharma), U.S. Patent Application Publication No. 20140066432 (Ventirx Pharma), U.S. Patent Application Publication No. 20140088085 (Ventirx Pharma), U.S. Patent Application Publication No. 20140275167 (Novira Examples of compounds disclosed in US Pat. Appl. Pub. No. 20130251673 (Novira Therapeutics) include those disclosed in US Pat.Exemplary TLR9 agonists that may be co-administered include, but are not limited to, AST-008, CMP-001, IMO-2055, IMO-2125, ritenimod, MGN-1601, BB-001, BB-006, IMO-3100, IMO-8400, IR-103, IMO-9200, agatolimod, DIMS-9054, DV-1079, DV-1179, AZD-1419, lefitolimod (MGN-1703), CYT-003, CYT-003-QbG10, and PUL-042. Examples of TLR3 agonists include lintatorimod, poly-ICLC, RIBOXXON®, Apoxxim, RIBOXXIM®, IPH-33, MCT-465, MCT-475, and ND-1.1.

[0143] Examples of TLR8 inhibitors include, but are not limited to, E-6887, IMO-8400, IMO-9200, and VTX-763.

[0144] Examples of TLR8 agonists include, but are not limited to, MCT-465, motolimod, GS-9688, and VTX-1463.

[0145] Examples of TLR9 agonists include, but are not limited to, AST-008, IMO-2055, IMO-2125, lefitolimod, ritenimod, MGN-1601, and PUL-042.

[0146] Examples of TLR7 / TLR8 agonists include, but are not limited to, NKTR-262, IMO-4200, MEDI-9197 (telluratolimod) and resiquimod.

[0147] Examples of TLR agonists include, but are not limited to, lefitolimod, tilsotolimod, lintatolimod, DSP-0509, AL-034, G-100, cobitolimod, AST-008, motolimod, GSK-1795091, GSK-2245035, VTX-1463, GS-9688, LHC-165, BDB-001, RG-7854, tellulatorimod.

[0148] In some embodiments, the therapeutic agent is a stimulator of interferon genes (STING). In some embodiments, the STING receptor agonist or activator is selected from ADU-S100 (MIW-815), SB-11285, MK-1454, SR-8291, AdVCA0848, GSK-532, SYN-STING, MSA-1, SR-8291, 5,6-dimethylxanthenone-4-acetic acid (DMXAA), cyclic GAMP (cGAMP), and cyclic-di-AMP.

[0149] TCR Signaling Modulators In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with one or more agonists or antagonists of T cell receptor (TCR) signaling modulators. Activation of T cells through the TCR is essential for thymocyte development and effector T cell function. TCR activation promotes signaling cascades that ultimately determine cell fate by regulating cytokine production, cell survival, proliferation, and differentiation. Examples of TCR signaling modulators include, but are not limited to, CD2 (cluster of differentiation 2, LFA-2, T11, LFA-3 receptor), CD3 (cluster of differentiation 3), CD4 (cluster of differentiation 4), CD8 (cluster of differentiation 8), CD28 (cluster of differentiation 28), CD45 (PTPRC, B220, GP180), LAT (linker for T cell activation, LAT1), Lck, LFA-1 (ITGB2, CD18, LAD, LCAMB), Src, Zap-70, SLP-76, DGK alpha, CBL-b, CISH, HPK1. Examples of cluster of differentiation 3 (CD3) agonists that may be co-administered include, but are not limited to, MGD015.

[0150] In various embodiments, the agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with one or more blockers or inhibitors of inhibitory immune checkpoint proteins or receptors, and / or one or more stimulators, activators, or agonists of one or more stimulatory immune checkpoint proteins or receptors. Blocking or inhibiting an inhibitory immune checkpoint may positively regulate T cell or NK cell activation and prevent immune evasion of cancer cells within the tumor environment. Activation or stimulation of a stimulatory immune checkpoint may enhance the effect of immune checkpoint inhibitors in cancer treatment. In various embodiments, an immune checkpoint protein or receptor regulates T cell responses (e.g., as reviewed in Xu, et al., J Exp Clin Cancer Res. (2018) 37:110). In various embodiments, immune checkpoint proteins or receptors regulate NK cell responses (reviewed, e.g., in Davis, et al., Semin Immunol. (2017) 31:64-75, and Chiossone, et al., Nat Rev Immunol. (2018) 18(11):671-688).

[0151] Examples of immune checkpoint proteins or receptors include, but are not limited to, CD27, CD70; CD40, CD40LG; CD47, CD48 (SLAMF2), transmembrane and immunoglobulin domain containing 2 (TMIGD2, CD28H), CD84 (LY9B, SLAMF5), CD96, CD160, MS4A1 (CD20), CD244 (SLAMF4); CD276 (B7H3); V-set domain-containing T-cell activation inhibitor 1 (VTCN1, B7H4); V-set immunoregulatory receptor (VSIR, B7H5, VISTA); immunoglobulin superfamily member 11 (IGSF11, VSIG3); natural killer cytotoxicity receptor 3 ligand 1 (NCR3LG1, B7H6); HERV-H LTR-associated 2 (HHLA2, B7H7); inducible T cell costimulatory molecule (ICOS, CD278); inducible T cell costimulatory molecule ligand (ICOSLG, B7H2); TNF receptor superfamily member 4 (TNFRSF4, OX40); TNF superfamily member 4 (TNFSF4, OX40L); TNFRSF8 (CD30), TNFSF8 (CD30L); TNFRSF10A (CD261, DR4, TRAILR1), TNFRSF9 (CD137), TNFSF9 (CD137L); TNFRSF10B (CD262, DR5, TRAILR2), TNFRSF10 (TRAIL); TNFRSF14 (HVEM, CD270), TNFSF14 (HVEML); CD272 (B and T lymphocyte-associated (BTLA));TNFRSF17 (BCMA, CD269), TNFSF13B (BAFF);TNFRSF18 (GITR), TNFSF18 (GITRL);MHC class I polypeptide-related sequence A (MICA);MHC class I polypeptide-related sequence B (MICB);CD274 (PDL1, PD-L1);Programmed cell death 1 (PDCD1, PD-1, PD-1);Cytotoxic T lymphocyte-associated protein 4 (CTLA4, CD152);CD80 (B7-1), CD28;Nectin cell adhesion molecule 2 (NECTIN2, CD112);CD226 (DNAM-1);Poliovirus receptor (PVR) cell adhesion molecule (PVR, CD155);T cell immunoreceptor with Ig and ITIM domains (TIGIT);T-cell immunoglobulin and mucin domain containing 4 (TIMD4; TIM4); Hepatitis A virus cellular receptor 2 (HAVCR2, TIMD3, TIM-3); Galectin 9 (LGALS9); Lymphocyte activation 3 (LAG-3, CD223); Signaling lymphocyte activation molecule family member 1 (SLAMF1, SLAM, CD150); Lymphocyte antigen 9 (LY9, CD229, SLAMF3); SLAM family member 6 (SLAMF 6, CD352); SLAM family member 7 (SLAMF7, CD319); UL16 binding protein 1 (ULBP1); UL16 binding protein 2 (ULBP2); UL16 binding protein 3 (ULBP3); retinoic acid early transcript 1E (RAET1E; ULBP4); retinoic acid early transcript 1G (RAET1G; ULBP5); retinoic acid early transcript 1L (RAET1L; ULBP6); lymphocyte activation 3 (CD223); Killer cell immunoglobulin-like receptor (KIR); Killer cell lectin-like receptor C1 (KLRC1, NKG2A, CD159A); Killer cell lectin-like receptor K1 (KLRK1, NKG2D, CD314); Killer cell lectin-like receptor C2 (KLRC2, CD159c, NKG2C); Killer cell lectin-like receptor C3 (KLRC3, NKG2E); Killer cell lectin-like receptor C4 (KLRC4, NKG2F); Killer cell immunoglobulin killer cell immunoglobulin-like receptor, one Ig domain, and long cytoplasmic tail 2 (KIR2DL1); killer cell immunoglobulin-like receptor, two Ig domains, and long cytoplasmic tail 2 (KIR2DL2); killer cell immunoglobulin-like receptor, three Ig domains, and long cytoplasmic tail 2 (KIR2DL3); killer cell immunoglobulin-like receptor, three Ig domains, and long cytoplasmic tail 1 (KIR3DL1); killer cell lectin-like receptor D1 (KLRD1).

[0152] In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with one or more blockers or inhibitors of one or more T cell inhibitory immune checkpoint proteins or receptors. Exemplary T cell inhibitory immune checkpoint proteins or receptors include, but are not limited to, CD274 (PDL1, PD-L1); programmed cell death 1 ligand 2 (PDCD1LG2, PD-L2, CD273); programmed cell death 1 (PDCD1, PD1, PD-1); cytotoxic T lymphocyte-associated protein 4 (CTLA4, CD152); CD276 (B7H3); V-set domain-containing inhibitor of T cell activation 1 (VTCN1, B7H4); V-set immunoregulatory receptor (VSIR, B7H5, VISTA); immunoglobulin superfamily member 11 (IGSF11, VSIG3); TNFRSF14 (HVEM, CD270), TNFSF14 (HVEML); CD272 (B and T lymphocyte-associated (BTLA)); PVR-associated related immunoglobulin domain containing (PVRIG, CD112R); T cell immunoreceptor with Ig and ITIM domains (TIGIT); lymphocyte activation 3 (LAG-3, CD223); Hepatitis A virus cell receptor 2 (HAVCR2, TIMD3, TIM-3); galectin 9 (LGALS9); killer cell immunoglobulin-like receptor (KIR); killer cell immunoglobulin-like receptor, one Ig domain, and long cytoplasmic tail 2 (KIR2DL1); killer cell immunoglobulin-like receptor, two Ig domains, and long cytoplasmic tail 2 (KIR2DL2); killer cell immunoglobulin-like receptor, three Ig domains, and long cytoplasmic tail 2 (KIR2DL3); and killer cell immunoglobulin-like receptor, three Ig domains, and long cytoplasmic tail 1 (KIR3DL1).

[0153] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with one or more agonists or activators of one or more T cell stimulatory immune checkpoint proteins or receptors. Exemplary T cell stimulatory immune checkpoint proteins or receptors include, but are not limited to, CD27, CD70; CD40, CD40LG; inducible T cell costimulatory molecule (ICOS, CD278); inducible T cell costimulatory molecule ligand (ICOSLG, B7H2); TNF receptor superfamily member 4 (TNFRSF4, OX40); TNF superfamily member 4 (TNFSF4, OX40L); TNFRSF9 (CD137), TNFSF9 (CD137L); TNFRSF18 (GITR), TNFSF18 (GITRL); CD80 (B7-1), CD28; nectin cell adhesion molecule 2 (NECTIN2, CD112); CD226 (DNAM-1); CD244 (2B4, SLAMF4), poliovirus receptor (PVR) cell adhesion molecule (PVR, CD155). See, e.g., Xu, et al., J Exp Clin Cancer Res. (2018) 37:110.

[0154] In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with one or more blockers or inhibitors of one or more NK cell inhibitory immune checkpoint proteins or receptors. Exemplary NK cell inhibitory immune checkpoint proteins or receptors include, but are not limited to, killer cell immunoglobulin-like receptor, three Ig domains and long cytoplasmic tail 1 (KIR, CD158E1); killer cell immunoglobulin-like receptor, one Ig domain and long cytoplasmic tail 2 (KIR2DL1); killer cell immunoglobulin-like receptor, two Ig domains and long cytoplasmic tail 2 (KIR2DL2); killer cell immunoglobulin-like receptor, three Ig domains and long cytoplasmic tail 2 (KIR2DL3); killer cell immunoglobulin-like receptor, three Ig domains and long cytoplasmic tail 1 (KIR3DL1); killer cell lectin-like receptor C1 (KLRC1, NKG2A, CD159A); and killer cell lectin-like receptor D1 (KLRD1, CD94).

[0155] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with one or more agonists or activators of one or more NK cell stimulatory immune checkpoint proteins or receptors. Exemplary NK cell stimulatory immune checkpoint proteins or receptors include, but are not limited to, CD16, CD226 (DNAM-1); CD244 (2B4, SLAMF4); Killer cell lectin-like receptor K1 (KLRK1, NKG2D, CD314); SLAM family member 7 (SLAMF7). See, e.g., Davis, et al., Semin Immunol. (2017) 31:64-75; Fang, et al., Semin Immunol. (2017) 31:37-54, and Chiossone, et al., Nat Rev Immunol. (2018) 18(11):671-688.

[0156] Adenosine Generation and Signaling In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are selected from the group consisting of agonists or antagonists of A1R, A2AR, A2BR, A3R, CD73, CD39, CD26, e.g., adenosine A3 receptor (A3R) agonists such as namodenoson (CF102); A2aR / A2bR antagonists such as AB928; anti-CD73 antibodies such as MEDI-9447 (oleculab), CPX-006, IPH-53, BMS-986179, NZV-930, CPI-006; AB-680, P Further combined with CD73 inhibitors such as SB-12379, PSB-12441, PSB-12425, CB-708, and those described in WO 19173692; CD39 / CD73 inhibitors such as PBF-1662; anti-CD39 antibodies, adenosine A2A receptor antagonists such as TTX-030, CPI-444, AZD-4635, preladenant, PBF-509; and adenosine deaminase inhibitors such as pentostatin, cladribine.

[0157] Bispecific T cell engagers In various embodiments, an agent that inhibits the binding between CD47 and SIRPα (e.g., magrolimab) and an anti-Trop-2 ADC (e.g., sacituzumab govitecan) described herein are further combined with a bispecific T cell engager (e.g., without Fc) or an anti-CD3 bispecific antibody (e.g., with Fc).Exemplary anti-CD3 bispecific antibodies or BiTEs that may be co-administered include AMG-160 (PSMA / CD3), AMG-212 (PSMA / CD3), AMG-330 (CD33 / CD3), AMG-420 (BCMA / CD3), AMG-427 (FLT3 / CD3), AMG-562 (CD19 / CD3), AMG-596 (EGFRvIII / CD3), AMG-701 (BCMA / CD3), AMG-757 (DLL3 / CD3), JNJ-64052781 (CD 19 / CD3), AMG-211 (CEA / CD3), BLINCYTO® (CD19 / CD3), RG7802 (CEA / CD3), ERY-974 (CD3 / GPC3), huGD2-BsAb (CD3 / GD2), PF-06671008 (cadherin / CD3), APVO436 (CD123 / CD3), ERY974, flotetuzumab (CD123 / CD3), GEM333 (CD3 / CD33), GEMoab (CD3 / PSCA), REGN-1979 ( CD20 / CD3), REGN-5678(PSMA / CD28), MCLA-117(CD3 / CLEC12A), JNJ-0819, JNJ-7564(CD3 / hem), JNJ-63709178(CD123 / CD3), MGD-0 07(CD3 / gpA33), MGD-009(CD3 / B7H3), IMCgp100(CD3 / gp100), XmAb-14045(CD123 / CD3), XmAb-13676(CD3 / CD20), XmAb-18087(SS TR2 / CD3), catumaxomab (CD3 / EpCAM), REGN-4018 (MUC16 / CD3), RG6026, RG6076, RG6194, RG-7828 (CD20 / CD3), CC-93269 (CD3 / BCMA), REGN-5458 (CD3 / BCMA), GRB-1302 (CD3 / Erbb2), GRB-1342 (CD38 / CD3), PF-06863135 (BCMA / CD3), SAR440234 (CD3 / CDw123). Optionally, the anti-CD3 binding bispecific molecule may or may not have an Fc.Exemplary bispecific T cell engagers that may be co-administered target CD3 and tumor associated antigens described herein, including, for example, CD19 (e.g., blinatumomab); CD33 (e.g., AMG330); CEA (e.g., MEDI-565); receptor tyrosine kinase-like orphan receptor 1 (ROR1) (Gohil, et al., Oncoimmunology. (2017) May 17; 6(7): e1326437); PD-L1 (Horn, et al., Oncotarget. 2017 Aug 3; 8(35): 57964-57980); and EGFRvIII (Yang, et al., Cancer Lett. 2017 Sep 10; 403: 224-230).

[0158] Bispecific and Trispecific Natural Killer (NK) Cell Engagers In various embodiments, the agents described herein that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 The ADC (e.g., sacituzumab govitecan) is further combined with a bispecific NK cell engager (BiKE) or trispecific NK cell engager (TriKE) (e.g., without Fc) or a bispecific antibody (e.g., with Fc) against an NK cell activating receptor, such as CD16A, C-type lectin receptors (CD94 / NKG2C, NKG2D, NKG2E / H, and NKG2F), natural cytotoxicity receptors (NKp30, NKp44, and NKp46), killer cell C-type lectin-like receptors (NKp65, NKp80), Fc receptors FcγR (mediating antibody-dependent cellular cytotoxicity), SLAM family receptors (e.g., 2B4, SLAM6, and SLAM7), killer cell immunoglobulin-like receptors (KIR) (KIR-2DS and KIR-3DS), DNAM-1, and CD137 (41BB). Exemplary anti-CD16 bispecific antibodies, BiKE, or TriKE that may be co-administered include AFM26 (BCMA / CD16A) and AFM-13 (CD16 / CD30). Optionally, the anti-CD16 binding bispecific molecule may or may not have an Fc. Exemplary bispecific NK cell engagers that may be co-administered target CD16 and one or more tumor-associated antigens described herein, including, for example, CD19, CD20, CD22, CD30, CD33, CD123, EGFR, EpCAM, ganglioside GD2, HER2 / neu, HLA class II, and FOLR1. BiKE and TriKE are described, for example, in Felices, et al., Methods Mol Biol. (2016) 1441:333-346; Fang, et al., Semin Immunol. (2017) 31:37-54.

[0159] Hematopoietic progenitor kinase 1 (HPK1) inhibitors In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an inhibitor of mitogen-activated protein kinase kinase kinase kinase 1 (MAP4K1, HPK1; NCBI Gene ID: 11184). Examples of inhibitors of hematopoietic progenitor kinase 1 (HPK1) include, but are not limited to, those described in WO 2018183956, WO 2018183964, WO 2018167147, WO 2018183964, WO 2016205942, WO 2018049214, WO 2018049200, WO 2018049191, WO 2018102366, WO 2018049152, WO 2020092528, WO 2020092621, and WO 2016090300.

[0160] Apoptosis signal-regulating kinase (ASK) inhibitors In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an ASK inhibitor, such as an inhibitor of mitogen-activated protein kinase kinase kinase 5 (MAP3K5; ASK1, MAPKKK5, MEKK5; NCBI gene ID: 4217). Examples of ASK1 inhibitors include, but are not limited to, those described in WO 2011 / 008709 (Gilead Sciences) and WO 2013 / 112741 (Gilead Sciences).

[0161] Bruton's tyrosine kinase (BTK) inhibitors In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an inhibitor of Bruton's tyrosine kinase (BTK, AGMX1, AT, ATK, BPK, IGHD3, IMD1, PSCTK1, XLA; NCBI Gene ID: 695). Examples of BTK inhibitors include, but are not limited to, (S)-6-amino-9-(1-(but-2-ynoyl)pyrrolidin-3-yl)-7-(4-phenoxyphenyl)-7H-purin-8(9H)-one, acalabrutinib (ACP-196), BGB-3111, CB988, HM71224, ibrutinib (Imbruvica), M-2951 (evobrutinib), M7583, tirabrutinib (ONO-4059), PRN-1008, spebrutinib (CC-292), TAK-020, becabrutinib, ARQ-531, SHR-1459, DTRMWXHS-12, TAS-5315, Calquence+AZD6738, Calquence+danvatirsen.

[0162] Cyclin-dependent kinase (CDK) inhibitors In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein inhibit the binding between cyclin-dependent kinase 1 (CDK1, CDC2; CDC28A; P34CDC2; NCBI Gene ID: 983); cyclin-dependent kinase 2 (CDK2, CDKN2; p33(CDK2); NCBI Gene ID: 1017); cyclin-dependent kinase 3 (CDK3; NCBI Gene ID: 1018); cyclin-dependent kinase 4 (CDK4, CMM3; PSK-J3; NCBI Gene ID: 10 19); cyclin-dependent kinase 6 (CDK6, MCPH12; PLSTIRE; NCBI Gene ID: 1021); cyclin-dependent kinase 7 (CDK7, CAK; CAK1; HCAK; MO15; STK1; CDKN7; p39MO15; NCBI Gene ID: 1022); or cyclin-dependent kinase 9 (CDK9, TAK; C-2k; CTK1; CDC2L4; PITALRE; NCBI Gene ID: 1025). Inhibitors of CDK1, 2, 3, 4, 6, 7, and / or 9 include, but are not limited to, abemaciclib, alvocidib (HMR-1275, flavopiridol), AT-7519, dinaciclib, ibrance, FLX-925, LEE001, palbociclib, ribociclib, rigosertib, selinexor, UCN-01, SY1365, CT-7001, SY-1365, G1T38, mirciclib, trilaciclib, PF-06873600, AZD4573, and TG-02.

[0163] Discoidin domain receptor (DDR) inhibitor. In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with inhibitors of discoidin domain receptor tyrosine kinase 1 (DDR1, CAK, CD167, DDR, EDDR1, HGK2, MCK10, NEP, NTRK4, PTK3, PTK3A, RTK6, TRKE; NCBI Gene ID: 780); and / or discoidin domain receptor tyrosine kinase 2 (DDR2, MIG20a, NTRKR3, TKT, TYRO10, WRCN; NCBI Gene ID: 4921). Examples of DDR inhibitors include, but are not limited to, dasatinib, and those disclosed in WO 2014 / 047624 (Gilead Sciences), U.S. Patent Application Publication No. 2009 / 0142345 (Takeda Pharmaceutical), U.S. Patent Application Publication No. 2011 / 0287011 (Oncomed Pharmaceuticals), WO 2013 / 027802 (Chugai Pharmaceutical), and WO 2013 / 034933 (Imperial Innovations).

[0164] Histone deacetylase (HDAC) inhibitors In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with inhibitors of histone deacetylase, e.g., histone deacetylase 9 (HDAC9, HD7, HD7b, HD9, HDAC, HDAC7, HDAC7B, HDAC9B, HDAC9FL, HDRP, MITR; Gene ID: 9734). Examples of HDAC inhibitors include, but are not limited to, abexinostat, ACY-241, AR-42, BEBT-908, belinostat, CKD-581, CS-055 (HBI-8000), CUDC-907 (fimepinostat), entinostat, gibinostat, mocetinostat, panobinostat, pracinostat, xinostat (JNJ-26481585), resminostat, ricolinostat, SHP-141, valproic acid (VAL-001), vorinostat, tinostamustine, remetinostat, entinostat, romidepsin, and tucidinostat.

[0165] Indoleamine-pyrrole-2,3-dioxygenase (IDO1) inhibitors In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1; NCBI Gene ID: 3620). Examples of IDO1 inhibitors include, but are not limited to, BLV-0801, epacadostat, F-001287, GBV-1012, GBV-1028, GDC-0919, indoximod, NKTR-218, NLG-919-based vaccines, PF-06840003, pyranonaphthoquinone derivatives (SN-35837), resminostat, SBLK-200802, BMS-986205, and shIDO-ST, EOS-200271, KHK-2455, LY-3381916.

[0166] Janus Kinase (JAK) Inhibitors In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with inhibitors of Janus kinase 1 (JAK1, JAK1A, JAK1B, JTK3; NCBI Gene ID: 3716); Janus kinase 2 (JAK2, JTK10, THCYT3; NCBI Gene ID: 3717); and / or Janus kinase 3 (JAK3, JAK-3, JAK3_HUMAN, JAKL, L-JAK, LJAK; NCBI Gene ID: 3718). Examples of JAK inhibitors include, but are not limited to, AT9283, AZD1480, baricitinib, BMS-911543, fedratinib, filgotinib (GLPG0634), gandotinib (LY2784544), INCB039110 (itacitinib), restortinib, momelotinib (CYT0387), NS-018, pacritinib (SB1518), peficitinib (ASP015K), ruxolitinib, tofacitinib (formerly tasocitinib), INCB052793, and XL019.

[0167] Matrix metalloproteinase (MMP) inhibitors In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are used in combination with inhibitors of matrix metallopeptidases (MMPs), such as MMP1 (NCBI Gene ID: 4312), MMP2 (NCBI Gene ID: 4313), MMP3 (NCBI Gene ID: 4314), MMP7 (NCBI Gene ID: 4316), MMP8 (NCBI Gene ID: 4317), MMP9 (NCBI Gene ID: 4318); MMP10 (NCBI Gene ID: 4319); MMP11 (NCBI Gene ID: 4320); MMP12 (NCBI Gene ID: 4321), MMP13 (NCBI Gene ID: 4322), MMP14 (NCBI Gene ID: 4323), MMP15 (NCBI Gene ID: 4324), MMP16 (NCBI Gene ID: 4325), MMP17 (NCBI Gene ID: 4326), MMP18 (NCBI Gene ID: 4327), MMP19 (NCBI Gene ID: 4330), MMP20 (NCBI Gene ID: 4331), MMP21 (NCBI Gene ID: 4332), MMP22 (NCBI Gene ID: 4333), MMP23 (NCBI Gene ID: 4334), MMP24 (NCBI Gene ID: 4335), MMP25 (NCBI Gene ID: 4336), MMP26 (NCBI Gene ID: 4337), MMP27 (NCBI Gene ID: 4338), MMP28 (NCBI Gene ID: 4339), MMP29 (NCBI Gene ID: 4340), MMP30 (NCBI Gene ID: 4341), MMP31 (NC and / or an inhibitor of MMP28 (NCBI Gene ID: 79148). Examples of MMP9 inhibitors include, but are not limited to, marimastat (BB-2516), sipemastat (Ro 32-3555), GS-5745 (andecaliximab), and those described in WO 2012 / 027721 (Gilead Biologics).

[0168] RAS and RAS pathway inhibitors In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein inhibit the binding between CD47 and SIRPα by inhibiting KRAS proto-oncogene, GTPase (KRAS; also known as NS; NS3; CFC2; RALD; K-Ras; KRAS1; KRAS2; RASK2; KI-RAS; CK-RAS; K-RAS2A; K-RAS2B; K-RAS4A; K-RAS4B; c-Ki-ras2; NCBI Gene ID: 3845); NRAS proto-oncogene, GTPase (NRAS; also known as NS6; CMNS; NC MS; ALPS4; N-ras; NRAS1; NCBI Gene ID: 4893); HRas proto-oncogene, further combined with an inhibitor of GTPase (HRAS; also known as CTLO; KRAS; HAMSV; HRAS1; KRAS2; RASH1; RASK2; Ki-Ras; p21ras; CH-RAS; cK-ras; H-RASIDX; c-Ki-ras; C-BAS / HAS; C-HA-RAS1; NCBI Gene ID: 3265). Ras inhibitors can inhibit Ras either at the polynucleotide level (e.g., transcription inhibitors) or at the polypeptide level (e.g., GTPase enzyme inhibitors). In some embodiments, the inhibitor targets one or more proteins in the Ras pathway, e.g., inhibiting one or more of EGFR, Ras, Raf (A-Raf, B-Raf, C-Raf), MEK (MEK1, MEK2), ERK, PI3K, AKT, and mTOR.

[0169] In various embodiments, an agent that inhibits the binding between CD47 and SIRPα (e.g., magrolimab) and an anti-Trop-2 ADC (e.g., sacituzumab govitecan) described herein is further combined with an inhibitor of KRAS. Examples of KRAS inhibitors include AMG-510, COTI-219, MRTX-1257, ARS-3248, ARS-853, WDB-178, BI-3406, BI-1701963, ARS-1620(G12C), SML-8-73-1(G12C), compound 3144(G12D), Kobe0065 / 2602(Ras GTP), RT11, MRTX-849(G12C), and K-RAS(G12D) selective inhibitory peptides, including KRpep-2(Ac-RRCPLYISYDPVCRR-NH2) (SEQ ID NO:256) and KRpep-2d(Ac-RRRRCPLYISYDPVCRRRR-NH2) (SEQ ID NO:257).

[0170] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with inhibitors of KRAS mRNA. Exemplary KRAS mRNA inhibitors include anti-KRAS U1 adaptor-, AZD-4785, siG12D-LODER™, and siG12D exosomes.

[0171] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with inhibitors of MEK. Exemplary MEK inhibitors that may be co-administered include binimetinib, cobimetinib, PD-0325901, pimasertib, RG-7304, selumetinib, trametinib, and selumetinib.

[0172] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with inhibitors of AKT. Exemplary AKT inhibitors that may be co-administered include RG7440, MK-2206, ipatasertib, afuresertib, AZD5363, and ARQ-092, capivasertib, triciribine, ABTL-0812 (PI3K / Akt / mTOR).

[0173] In various embodiments, the agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with inhibitors of Raf. Exemplary Raf inhibitors that may be co-administered include BGB-283 (Raf / EGFR), HM-95573, LXH-254, LY-3009120, RG7304, TAK-580, dabrafenib, vemurafenib, encorafenib (LGX818), PLX8394. RAF-265 (Raf / VEGFR), ASN-003 (Raf / PI3K).

[0174] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with inhibitors of ERK. Exemplary ERK inhibitors that may be co-administered include LTT-462, LY-3214996, MK-8353, ravoxertinib, GDC-0994, and ulixertinib.

[0175] In various embodiments, the agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with inhibitors of PI3K. Exemplary PI3K inhibitors that may be co-administered include idelalisib (Zydelig®), alpelisib, buparlisib, pitilisib, eganelisib (IPI-549). Exemplary PI3K / mTOR inhibitors that may be co-administered include dactolisib, omipalisib, voxtalisib, gedatolicib, GSK2141795, RG6114.

[0176] In various embodiments, the agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with inhibitors of mTOR. Exemplary mTOR inhibitors that may be co-administered include sapoanisertib, bistusertib (AZD2014), ME-344, sirolimus (oral nano-amorphous formulation, cancer), TYME-88 (mTOR / cytochrome P450 3A4).

[0177] In certain embodiments, Ras-driven cancers (e.g., NSCLC) with CDKN2A mutations can be inhibited by co-administration of the MEK inhibitor selumetinib and the CDK4 / 6 inhibitor palbociclib. See, e.g., Zhou, et al., Cancer Lett. 2017 Nov 1; 408: 130-137. Also, K-RAS and mutant N-RAS can be reduced by the irreversible inhibitor neratinib of ERBB1 / 2 / 4. See, e.g., Booth, et al., Cancer Biol Ther. 2018 Feb 1; 19(2): 132-137.

[0178] In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with inhibitors of the RAS. Examples of RAS inhibitors include NEO-100 and rigosertib.

[0179] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an EGFR antagonist, such as AMG-595, necitumumab, ABBV-221, depatuxizumab mafodotin (ABT-414), tomzotuximab, ABT-806, Vectibix®, modotuximab, or RM-1929.

[0180] In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with inhibitors of protein tyrosine phosphatase non-receptor type 11 (PTPN11; BPTP3, CFC, JMML, METCDS, NS1, PTP-1D, PTP2C, SH-PTP2, SH-PTP3, SHP2; NCBI gene ID: 5781). Examples of SHP2 inhibitors include TNO155 (SHP-099), RMC-4550, JAB-3068, RMC-4630, SAR442720, and those described in WO2018172984 and WO2017211303.

[0181] In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an inhibitor of mitogen-activated protein kinase 7 (MAP2K7, JNKK2, MAPKK7, MEK, MEK7, MKK7, PRKMK7, SAPKK-4, SAPKK4; NCBI Gene ID: 5609). Examples of MEK inhibitors include antroquinol, binimetinib, CK-127, cobimetinib (GDC-0973, XL-518), MT-144, selumetinib (AZD6244), sorafenib, trametinib (GSK1120212), uprosertib + trametinib, PD-0325901, pimasertib, LTT462, AS703988, CC-90003, refametinib, TAK-733, CI-1040, and RG7421.

[0182] In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein inhibit the binding of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit, e.g., phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA, CLAPO, CLOVE, CWS5, MCAP, MCM, MCMTC, PI3K, PI3K-alpha, p110-alpha; NCBI Gene ID: 5290); phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta (PIK3CB, P110BETA, PI3K, PI3KBETA, PIK3C1; NCBI Gene ID: 5291); phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG, PI3CG, PI3K, PI3K gamma, PIK3, p110 gamma, p120-PI3K; Gene ID: 5494);and / or an inhibitor of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (PIK3CD, APDS, IMD14, P110delta, PI3K, p110D, NCBI gene ID: 5293). In some embodiments, the PI3K inhibitor is a pan-PI3K inhibitor. Examples of PI3K inhibitors include ACP-319, AEZA-129, AMG-319, AS252424, AZD8186, BAY 1082439, BEZ235, bimiralisib (PQR309), bupallisib (BKM120), BYL719 (alpelisib), carboxyamidotriazole orotate (CTO), CH5132799, CLR-457, CLR-1401, copanlisib (BAY 1082439), ... 80-6946), DS-7423, dactolisib, duvelisib (IPI-145), fimepinostat (CUDC-907), gedatolisib (PF-05212384), GDC-0032, GDC-0084 (RG7666), GDC-0077, pictilisib (GDC-0941), GDC-0980, GSK2636771, GSK2269577, GSK2141795, idelalisib (Zydelig®), I NCB040093, INCB50465, IPI-443, IPI-549, KAR4141, LY294002, LY3023414, NERLYNX® (neratinib), nemiralisib (GSK2269557), omipalisib (GSK2126458, GSK458), OXY111A, panulisib (P7170, AK151761), PA799, perifosine (KRX-0401), piralalisib (SAR245408);XL147), pukitinib mesylate (XC-302), SAR260301, seravelisib (UCB-5857), seravelisib (INK-1117, MLN-1117, TAK-117), SF1126, sonolisib (PX-866), RG6114, RG7604, rigosertib sodium (ON-01910 sodium), RP5090, tenalisib (RP6530), RV-172 9, SRX3177, taselisib, TG100115, umbralisib (TGR-1202), TGX221, voxtalisib (SAR245409), VS-5584, WX-037, X-339, X-414, XL499, XL756, wortmannin, ZSTK474, and the compounds disclosed in International Publication No. 2005 / 113556 (ICOS), International Publication No. 2013 / 052699 (Gilead Calistoga), WO 2013 / 116562 (Gilead Calistoga), WO 2014 / 100765 (Gilead Calistoga), WO 2014 / 100767 (Gilead Calistoga), and WO 2014 / 201409 (Gilead Sciences);

[0183] Spleen Tyrosine Kinase (SYK) Inhibitors In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an inhibitor of spleen-associated tyrosine kinase (SYK, p72-Syk, Gene ID: 6850). Examples of SYK inhibitors include, but are not limited to, 6-(1H-indazol-6-yl)-N-(4-morpholinophenyl)imidazo[1,2-a]pyrazin-8-amine, BAY-61-3606, celduratinib (PRT-062607), enstopretinib, fostamatinib (R788), HMPL-523, NVP-QAB 205 AA, R112, R343, tamatinib (R406), and those described in U.S. Pat. No. 8,450,321 (Gilead Connecticut), and those described in U.S. Patent Application Publication No. 2015 / 0175616.

[0184] Tyrosine kinase inhibitors (TKIs) In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with a tyrosine kinase inhibitor (TKI) that may target the epidermal growth factor receptor (EGFR) and receptors for fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF). Examples of TKIs include, but are not limited to, axitinib, afatinib, ARQ-087 (derazantinib), asp5878, AZD3759, AZD4547, bosutinib, brigatinib, cabozantinib, cediranib, crenolanib, crizotinib, dacomitinib, dasatinib, dovitinib, E-6201, erdafitinib, erlotinib, gefitinib, gilteritinib (ASP-2215), FP-1039, HM61713, icotinib, imatinib, K X2-391 (Src), lapatinib, restortinib, lenvatinib, midostaurin, nintedanib, ODM-203, olmutinib, osimertinib (AZD-9291), pazopanib, ponatinib, poziotinib, quizartinib, radotinib, rociletinib, surufatinib (HMPL-012), sunitinib, famitinib L-malate, (MAC-4), TH-4000, tivoanib, MEDI-575 (anti-PDGFR antibody), and TAK-659.

[0185] Chemotherapy (standard treatment) In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with a chemotherapeutic or anti-tumor agent.

[0186] As used herein, the term "chemotherapeutic agent" or "chemotherapeutic agent" (or "chemotherapy" in the case of treatment with a chemotherapy drug) is meant to encompass any non-proteinaceous (e.g., non-peptidic) compound useful in the treatment of cancer. Examples of chemotherapeutic agents include, but are not limited to, alkylating agents such as thiotepa and cyclophosphamide (CYTOXAN®); alkyl sulfonates such as busulfan, improsulfan, and piposulfan; aziridines such as benzodepa, carboquone, meturedepa, and uredepa; ethylenimines and methylamelanamines, including altretamine, triethylenemelamine, triethylenephosphoramide, triethylenethiophosphoramide, and trimerylomelanamine; acetogenins such as bullatacin and bullatacinone; camptothecins, including the synthetic analog topotecan; bryostatin, kallistatin; CC-1065, including the synthetic analogs adozelesin, carzelesin, and bizeresin; cryptoxanthin, which are useful in the treatment of cancer. phycins, especially cryptophycin 1 and cryptophycin 8; dolastatins; duocarmycins, including synthetic analogs KW-2189 and CBI-TMI; eleutherobin; 5-azacytidine; pancratistatin; sarcodictyin; spongistatins; nitrogen mustards, such as chlorambucil, chlornaphazine, cyclophosphamide, glufosfamide, evofosfamide, bendamustine, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembitine, phenesterine, prednimustine, trofosfamide, and uracil mustard; nitrosoureas, such as carmustine, chlorozotocin, foremstine, lomustine, nimustine, and ranimustine;Antibiotics, such as enediyne antibiotics (e.g., calicheamicins, especially calicheamicin gamma II and calicheamicin phi I1), dynemicins, including dynemicin A, bisphosphonates such as clodronate, esperamicin, neocarzinostatin chromophore and related chromoprotein enediyne antibiotic chromophores, aclacinomycin, actinomycin, anthramycin, azaserine, bleomycin, cactinomycin, carabimycin, carminomycin, carzinophilin, chromoproteins ... doxorubicin, dactinomycin, daunorubicin, detorubicin, 6-diazo-5-oxo-L-norleucine, doxorubicin (including morpholino-doxorubicin, cyanomorpholino-doxorubicin, 2-pyrrolino-doxorubicin, and deoxydoxorubicin), epirubicin, esorubicin, idarubicin, marcelomycin, mitomycins such as mitomycin C, mycophenolic acid, nogalamycin, olivomycin, peplomycin, porfiromycin, puromycin, keramycin, and lomimycin. dorbicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, and zorubicin; antimetabolites such as methotrexate and 5-fluorouracil (5-FU); folic acid analogs such as demopterin, methotrexate, pteropterin, and trimetrexate; purine analogs such as cladribine, pentostatin, fludarabine, 6-mercaptopurine, thiamiprine, and thioguanine; pyrimidine analogs such as ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, and floxuridine; androgens such as calsterone, dromostanolone propionate, epithiostanol, mepitiostane, and testolactone; antiadrenal drugs such as aminoglutethimide, mitotane, and trilostane; folic acid supplements such as floric acid; radiotherapeutic agents such as radium-223, 177-Lu-PSMA-617; trichothecenes, especially T-2 toxin, veracrine A, roridin A, and anguidine;Taxoids such as paclitaxel (TAXOL®), albumin-bound paclitaxel or nab-paclitaxel (ABRAXANE®), docetaxel (TAXOTERE®), cabazitaxel, BIND-014, tesetaxel; platinum analogues such as cisplatin and carboplatin, NC-6004 nanoplatin; aceglatone; aldophosphamide glycosides; aminolevulinic acid; eniluracil; amsa Clin;Hestrabucil;Bisantrene;Edatrexate;Defofamine;Demecolcine;Diaziquone;Elformucine;Elliptinium acetate;Epothilone;Etoglucide;Gallium nitrate;Hydroxyurea;Lentinan;Leucovorin;Lonidamine;Maytansinoids, such as maytansine and ansamitocin;Mitoguazone;Mitoxantrone;Mopidamol;Nitracrine;Phenamet;Pirarubicin;Rosoxantrone;Fluoropyrimidines ;Folinic acid;Podophyllic acid, 2-ethylhydrazide;Procarbazine;Polysaccharide K (PSK);Razoxane;Rhizoxin;Sizofiran;Spirogermanium;Tenuazonic acid;Trabectedin, Triaziquone;2,2',2''-Trichlorotriemylamine;Urethane;Vindesine;Dacarbazine;Mannomustine;Mitobronitol;Mitolactol;Pipobroman;Gacytosine;Arabinoside ("Ara-C");Cyclophosphamide; Thiotepa;Chlorambucil;Gemcitabine (GEMZAR®);6-Thioguanine;Mercaptopurine;Methotrexate;Vinblastine;Platinum;Etoposide (VP-16);Ifosfamide;Mitoxantrone;Vancristine;Vinorelbine (NAVELBINE®);Novantrone;Teniposide;Edatrexate;Daunomycin, Aminopterin, Xeloda;Ibandronate;CPT-11;Topoisomerase inhibitors RFS 2000;Difluoromethylornithine (DFMO);Retinoids, e.g., retinoic acid;Capecitabine;NUC-1031;FOLFOX (Folinic acid, 5-fluorouracil, oxaliplatin);FOLFIRI (Folinic acid, 5-fluorouracil, irinotecan);These include FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, irinotecan), FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan, oxaliplatin), as well as pharma- ceutically acceptable salts, acids, or derivatives of any of the above. Such agents may be conjugated to an antibody or any of the targeting agents described herein to create an antibody drug conjugate (ADC) or targeted drug conjugate;

[0187] Also included within the definition of "chemotherapeutic agent" are antihormonal agents such as antiestrogens and selective estrogen receptor modulators (SERMs), inhibitors of the enzyme aromatase, antiandrogens, and pharma- ceutically acceptable salts, acids, or derivatives of any of the above that act to modulate or inhibit hormone action on tumors. Examples of antiestrogens and SERMs include, for example, tamoxifen (including NOLVADEX™), raloxifene, droloxifene, 4-hydroxytamoxifen, trioxyfene, keoxyfene, LY117018, onapristone, and toremifene (FARESTON®). Inhibitors of the enzyme aromatase regulate estrogen production in the adrenal gland. Examples include 4(5)-imidazole, aminoglutethimide, megestrol acetate (MEGACE®), exon 100, cyclosporine ... Examples of antiandrogens include semestane, formestane, fadrozole, vorozole (RIVISOR®), letrozole (FEMARA®), and anastrozole (ARIMIDEX®). Examples of antiandrogens include apalutamide, abiraterone, enzalutamide, flutamide, galeterone, nilutamide, bicalutamide, leuprolide, goserelin, ODM-201, APC-100, and ODM-204. Examples of progesterone receptor antagonists include onapristone.

[0188] Antiangiogenic Agents In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-angiogenic agent. Antiangiogenic agents that may be co-administered include, but are not limited to, retinoid acid and its derivatives, 2-methoxyestradiol, ANGIOSTATIN®, ENDOSTATIN®, regorafenib, necupranib, suramin, squalamine, tissue inhibitor of metalloproteinase-1, tissue inhibitor of metalloproteinase-2, plasminogen activator inhibitor-1, plasminogen activator inhibitor-2, cartilage-derived inhibitor, paclitaxel (nab-paclitaxel), platelet factor 4, protamine sulfate (clupeine), sulfated chitin derivatives (prepared from snow crab shells), sulfated polysaccharide peptidoglycan complex (sp-pg), staurosporine, proline analogs such as l-azetidine-2-carboxylic acid (LACA), modulators of matrix metabolism, such as cis-hydroxyproline, d,I-3,4-dehydroproline, metalloproteinase inhibitors such as thiaproline, α,α'-dipyridyl, beta-aminopropionitrile fumarate, 4-propyl-5-(4-pyridinyl)-2(3h)-oxazolone, methotrexate, mitoxantrone, heparin, interferon, 2 macroglobulin serum, chicken inhibitor of metalloproteinase-3 (ChIMP-3), chymostatin, beta-cyclodextrin tetradecasulfate, eponemycin, fumagillin, gold sodium thiomalate, d-penicillamine, beta-1-anticollagenase serum, alpha-2-antiplasmin, bisantrene, lobenzarit disodium, n-2-carboxyphenyl-4-chloroanthonylate disodium or "CCA", thalidomide, angiogenesis-suppressing steroids, carboxyaminoimidazole, metalloproteinase inhibitors such as BB-94, and S100A9 inhibitors such as tasquinimod. Other anti-angiogenic agents include antibodies, preferably monoclonal antibodies against the following angiogenic growth factors: beta-FGF, alpha-FGF, FGF-5, VEGF isoforms, VEGF-C, HGF / SF, and Ang-1 / Ang-2.

[0189] Antifibrotic Agents In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-fibrotic agent. Anti-fibrotic agents that may be co-administered include, but are not limited to, compounds such as beta-aminopropionitrile (BAPN) and those disclosed in U.S. Pat. No. 4,965,288 for inhibitors of lysyl oxidase and their use in treating diseases and conditions associated with abnormal deposition of collagen, and U.S. Pat. No. 4,997,854 for compounds that inhibit LOX for the treatment of various pathological fibrotic conditions, which are incorporated herein by reference. Further exemplary inhibitors are described in U.S. Pat. No. 4,943,593, U.S. Pat. No. 5,021,456, U.S. Pat. No. 5,059,714, U.S. Pat. No. 5,120,764, U.S. Pat. No. 5,182,297, U.S. Pat. No. 5,252,608, U.S. Pat. No. 2-(1-naphthyloxymemyl)-3-fluoroallylamine, and U.S. Patent Application Publication No. 2004 / 0248871, which are incorporated herein by reference.

[0190] Exemplary antifibrotic agents include primary amines that react with the carbonyl group of the active site of lysyl oxidase, more specifically, those that generate products stabilized by resonance after binding to the carbonyl, such as the following primary amines: emilenmamine, hydrazine, phenylhydrazine, and their derivatives; semicarbazide and urea derivatives; aminonitriles, such as BAPN or 2-nitroethylamine; unsaturated or saturated haloamines, such as 2-bromo-ethylamine, 2-chloroethylamine, 2-trifluoroethylamine, 3-bromopropylamine, and p-halobenzylamines; and selenohomocysteine ​​lactones.

[0191] Other antifibrotic agents are copper chelators that may or may not permeate cells. Exemplary compounds include indirect inhibitors that inhibit the aldehyde derivatives derived from the oxidative deamination of lysyl and hydroxylysyl residues by lysyl oxidase. Examples include thiolamines, particularly D-penicillamine and its analogs, such as 2-amino-5-mercapto-5-methylhexanoic acid, D-2-amino-3-methyl-3-((2-acetamidoethyl)dithio)butanoic acid, p-2-amino-3-methyl-3-((2-aminoethyl)dithio)butanoic acid, sodium-4-(((p-1-dimethyl-2-amino-2-carboxyethyl)dithio)butane sulfate, 2-acetamidoethyl-2-acetamidoethanethiolsulfanate, and sodium-4-mercaptobutanesulfinate trihydrate.

[0192] Anti-inflammatory agents In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with an anti-inflammatory agent. Exemplary anti-inflammatory agents include, but are not limited to, arginase (ARG1 (NCBI Gene ID: 383), ARG2 (NCBI Gene ID: 384)), carbonic anhydrase (CA1 (NCBI Gene ID: 759), CA2 (NCBI Gene ID: 760), CA3 (NCBI Gene ID: 761), CA4 (NCBI Gene ID: 762), CA5A (NCBI Gene ID: 763), CA5B (NCBI Gene ID: 11238), CA6 (NCBI Gene ID: 765), CA7 (NCBI Gene ID: 766), CA8 (NCBI Gene ID: 767), CA9 (NCBI Gene ID: 768), CA10 (NCBI Gene ID: 56934), CA11 (NCBI Gene ID: 770), CA12 (NCBI Gene ID: 771), CA13 (NCBI Gene ID: 377677), CA14 (NCBI Gene ID: 23632)), prostaglandin endoperoxide synthase 1 (PTGS1, COX-1; NCBI Gene ID: 5742), prostaglandin endoperoxide synthase 2 (PTGS2, COX-2; NCBI Gene ID: 5743), secretory phospholipase A2, prostaglandin E synthase (PTGES, PGES; Gene ID: 9536), arachidonate 5-lipoxygenase (ALOX5, 5-LOX; NCBI Gene ID: 240), soluble epoxide hydrolase 2 (EPHX2, SEH; NCBI Gene ID: 2053), and / or mitogen-activated protein kinase kinase kinase 8 (MAP3K8, TPL2; NCBI Gene ID: 1326). In some embodiments, the inhibitor is a dual inhibitor, for example, a COX-2 / COX-1, COX-2 / SEH, COX-2 / CA, COX-2 / 5-LOX dual inhibitor.

[0193] Examples of inhibitors of prostaglandin endoperoxide synthase 1 (PTGS1, COX-1; NCBI gene ID: 5742) that may be co-administered include, but are not limited to, mofezolac, GLY-230, and TRK-700.

[0194] Examples of inhibitors of prostaglandin endoperoxide synthase 2 (PTGS2, COX-2; NCBI Gene ID: 5743) that may be co-administered include, but are not limited to, diclofenac, meloxicam, parecoxib, etoricoxib, AP-101, celecoxib, AXS-06, diclofenac potassium, DRGT-46, AAT-076, maceoshuri, lumiracoxib, meloxicam, valdecoxib, zaltoprofen, nimesulide, anitrazafen, apricoxib, cimicoxib, deracoxib, flumisole, firocoxib, macoxib, NS-398, pamicogrel, parecoxib, robenacoxib, rofecoxib, rutaecarpine, tilmacoxib, and zaltoprofen. Examples of COX1 / COX2 dual inhibitors that may be co-administered include, but are not limited to, HP-5000, lornoxicam, ketorolac tromethamine, bromfenac sodium, ATB-346, HP-5000. Examples of COX-2 / carbonic anhydrase (CA) dual inhibitors that may be co-administered include, but are not limited to, pormacoxib and imrecoxib.

[0195] Examples of inhibitors of secretory phospholipase A2, prostaglandin E synthase (PTGES, PGES; Gene ID: 9536) that may be co-administered include, but are not limited to, LY3023703, GRC 27864, and the compounds described in WO 2015158204, WO 2013024898, WO 2006063466, WO 2007059610, WO 2007124589, WO 2010100249, WO 2010034796, WO 2010034797, WO 2012022793, WO 2013024898 ... International Publication No. 2012076673, International Publication No. 2012076672, International Publication No. 2010034798, International Publication No. 2010034799, International Publication No. 2012022792, International Publication No. 2009103778, International Publication No. 2011048004, International Publication No. 2012087771, International Publication No. 2012161965, International Publication No. 2013118 071, International Publication No. 2013072825, International Publication No. 2014167444, International Publication No. 2009138376, International Publication No. 2011023812, International Publication No. 2012110860, International Publication No. 2013153535, International Publication No. 2009130242, International Publication No. 2009146696, International Publication No. 2013186692, International Publication No. 2 Examples of compounds that can be used include those described in International Publication Nos. 015059618, 2016069376, 2016069374, 2009117985, 2009064250, 2009064251, 2009082347, 2009117987, and 2008071173. Additionally, metformin has been found to inhibit the COX2 / PGE2 / STAT3 axis and can be co-administered. See, for example, Tong, et al., Cancer Lett. (2017) 389: 23-32, and Liu, et al., Oncotarget. (2016) 7(19): 28235-46.

[0196] Carbonic anhydrases that may be co-administered (e.g., CA1 (NCBI Gene ID: 759), CA2 (NCBI Gene ID: 760), CA3 (NCBI Gene ID: 761), CA4 (NCBI Gene ID: 762), CA5A (NCBI Gene ID: 763), CA5B (NCBI Gene ID: 11238), CA6 (NCBI Gene ID: 765), CA7 (NCBI Gene ID: 766), CA8 (NCBI Gene ID: 767), CA9 (NCBI Gene ID: 768), Examples of inhibitors of one or more of CA10 (NCBI Gene ID: 768), CA10 (NCBI Gene ID: 56934), CA11 (NCBI Gene ID: 770), CA12 (NCBI Gene ID: 771), CA13 (NCBI Gene ID: 377677), CA14 (NCBI Gene ID: 23632) include, but are not limited to, acetazolamide, methazolamide, dorzolamide, zonisamide, brinzolamide, and diclophenamide. Dual COX-2 / CA1 / CA2 inhibitors that may be co-administered include CG100649.

[0197] Examples of inhibitors of arachidonate 5-lipoxygenase (ALOX5, 5-LOX; NCBI gene ID: 240) that may be co-administered include, but are not limited to, meclofenamate sodium, zileuton.

[0198] Examples of soluble epoxide hydrolase 2 (EPHX2, SEH; NCBI Gene ID: 2053) inhibitors that may be co-administered include, but are not limited to, compounds described in WO2015148954. Dual COX-2 / SEH inhibitors that may be co-administered include compounds described in WO2012082647. Dual SEH and fatty acid amide hydrolase (FAAH; NCBI Gene ID: 2166) inhibitors that may be co-administered include compounds described in WO2017160861.

[0199] Examples of inhibitors of mitogen-activated protein kinase kinase kinase 8 (MAP3K8, tumor progression locus 2, TPL2; NCBI Gene ID: 1326) that may be co-administered include, but are not limited to, GS-4875, GS-5290, BHM-078, as well as those described in, for example, WO 2006124944, WO 2006124692, WO 2014064215, WO 2018005435, Teli, et al., J Enzyme Inhib Med Chem. (2012) 27(4):558-70; Gangwall, et al., Curr Top Med Chem. (2013) 13(9):1015-35; Wu, et al., Bioorg Med Chem. Lett. (2009) 19(13):3485-8; Kaila, et al., Bioorg Med Chem. (2007) 15(19):6425-42; and Hu, et al., Bioorg Med Chem Lett. (2011) 21(16):4758-61.

[0200] Tumor oxygenators In various embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with agents that promote or increase tumor oxygenation or reoxygenation, or prevent or reduce tumor hypoxia. Exemplary agents that may be co-administered include, for example, hypoxia inducible factor-1 alpha (HIF-1α) inhibitors, e.g., PT-2977, PT-2385; VEGF inhibitors, e.g., bevacizumab, IMC-3C5, GNR-011, tanibirumab, LYN-00101, ABT-165; and / or oxygen carrier proteins such as OMX-302 and HNOX proteins (e.g., heme-nitric oxide and / or oxygen binding protein (HNOX)), e.g., as described in WO 2007 / 137767, WO 2007 / 139791, WO 2014 / 107171, and WO 2016 / 149562.

[0201] Immunotherapeutic agents In various embodiments, an agent that inhibits the binding between CD47 and SIRPα (e.g., magrolimab) and an anti-Trop-2 ADC (e.g., sacituzumab govitecan) described herein is further combined with an immunotherapeutic agent.Examples of immunotherapeutic agents that may be co-administered include abagovomab, ABP-980, adecatumumab, afutumumab, alemtuzumab, altumomab, amatuximab, anatumomab, arcitunomab, bavituximab, bectumomab, bevacizumab biosimilar, bivatuzumab, blinatumab, brentuximab, cantuzumab, catumaxomab, CC49, cetuximab, sitatuzumab, cixutumumab, clivatuzumab, conatumumab, dacetuzumab, darotuzumab, daratuzumab, detumomab, dinutuximab, docetaximab, and darotuzumab. Logitumab, durigotumab, dusigitumab, ecromeximab, emibetuzumab, ensituzumab, ertumaxomab, etaracizumab, farletuzumab, figitumumab, framvotumab, futuximab, gemtuzumab, girentuximab, glenbatumumab, ibritumomab, igovomab, imgatuzumab, indatuximab, inotumomab, intetumumab, ipilimumab (YERVOY®, MDX-010, BMS-734016, and MDX-101), iratumumab, labetuzumab, lexa tuzumab, lintuzumab, lorvotuzumab, lucatumumab, matuzumab, milatuzumab, minletuzumab, mitumomab, moxetumomab, moxetumomab-passudotox, naptumomab, narutuzumab, necitumumab, nimotuzumab, nofetumomab, OBI-833, obinutuzumab, ocaratuzumab, ofatumumab, olaratuzumab, onartuzumab, oportuzumab, oregovomab, panitumumab, palsatuzumab, passudotox, patritumab, pemtumomab, pertuzumab, pintumomab, pritumumab, laco These include, but are not limited to, tumomab, radletuzumab, ramucirumab (Cyramza®), rilotumumab, rituximab, lobatumumab, samalizumab, satumomab, sibrotuzumab, siltuximab, solitomab, simtuzumab, tacatuzumab, taplitumomab, tenatumomab, teprotumumab, tigatuzumab, tositumomab, trastuzumab, biosimilar of trastuzumab, tucotuzumab, ubirituximab, veltuzumab, borsetuzumab, votumumab, zalutumumab, and 3F8.Rituximab can be used to treat indolent B-cell cancers, including marginal zone lymphoma, WM, CLL, and small lymphocytic lymphoma. The combination of rituximab and chemotherapy agents is particularly effective.

[0202] The exemplified therapeutic antibodies may further be labeled with or combined with radioisotope particles such as indium-111, yttrium-90 (90Y clivatuzumab), or iodine-131.

[0203] In some embodiments, the immunotherapeutic agent is an antibody drug conjugate (ADC). Exemplary ADCs that may be co-administered include, but are not limited to, drug-conjugated antibodies, fragments thereof, or antibody mimetics that target the proteins or antigens listed above and herein (e.g., Table B). Exemplary ADCs that may be co-administered include, but are not limited to, gemtuzumab, brentuximab, trastuzumab, inotuzumab, glembatumumab, anetumab, mirvetuximab, depatuximab, novalpituzumab, vadastuximab, labetuzumab, rifastuzumab, indusatuzumab, polatuzumab, pinatuzumab, cortuximab, indatuximab, milatuzumab, rovalpituzumab, ABBV-011, ABBV-2029, ABBV-3 21, ABBV-647, MLN0264 (anti-GCC, guanylyl cyclase C), T-DM1 (trastuzumab emtansine, Kadcycla); SYD985 (anti-HER2, duocarmycin), milatuzumab doxorubicin (hCD74-DOX), DCDT2980S, belantamab mafodotin (GSK2857916), polatuzumab vedotin (RG-7596), SGN-CD70A, SGN-CD19A, inotuzumab ozogamicin (CMC-544) , lorvotuzumab mertansine, SAR3419, isactuzumab govitecan, enfortumab vedotin (ASG-22ME), ASG-15ME, DS-8201 ((trastuzumab deruxtecan), 225Ac-lintuzumab, U3-1402, 177Lu-tetraxetane-tetuloma, tisotumab vedotin, anetumab ravtansine, CX-2009, SAR-566658, W-0101, ABBV-085, gemtuzumab ozogamicin, ABT-414, Glenbatumumab vedotin (CDX-011), labetuzumab govitecan (IMMU-130), rifasuzumab vedotin, (RG-7599), milatuzumab doxorubicin (IMMU-110), indatuximab ravtansine (BT-062), pinatuzumab vedotin (RG-7593), SGN-LIV1A, SGN-CD33A, SAR566658, MLN2704, SAR408701, rovalpituzumab tesirine, ABBV-399, AGS-16C3F,ASG-22ME, AGS67E, AMG172, AMG595, AGS-15E, BAY1129980, BAY1187982, BAY94-934 (anetumab vedotin), GSK2857916, Humax-TF-ADC (tisotumab vedotin), IMGN289, IMGN529, IMGN853 (mirvetuximab soravtansine), LOP628, PCA062, MDX-1203, MEDI-5 47, PF-06263507, PF-06647020, PF-06647263, PF-06664178, PF-06688992, PF-06804103, RG7450, RG7458, RG7598, SAR566658, SGN-CD33A, DS-1602, and DS-7300, DS-6157, DS-6000, TAK-164, MEDI2228, MEDI7247, AMG575. ADCs that can be co-administered are described, for example, in Lambert, et al., Adv Ther (2017) 34: 1015-1035 and de Goeij, Current Opinion in Immunology (2016) 40: 14-23.

[0204] Exemplary therapeutic agents (e.g., anti-cancer or anti-tumor agents) that can be conjugated to a drug-conjugated antibody, fragment thereof, or antibody mimetic include, but are not limited to, monomethyl auristatin E (MMAE), monomethyl auristatin F (MMAF), calicheamicins, ansamitocins, maytansine or analogs thereof (e.g., mertansine / emtansine (DM1), ravtansine / soravtansine (DM4)), anthracyclines (e.g., doxorubicin, daunorubicin, epirubicin, idarubicin), pyrrolobenzodiazepine (PBD) DNA crosslinker SC-DR002 (D6.5), duocarmycins, microtubule inhibitors (MTIs) (e.g., taxanes, vinca alkaloids, epothilones), pyrrolobenzodiazepine (PBD) or dimers thereof, duocarmycins (A, B1, B2, C1, C2, D, SA, CC-1065) and other anti-cancer or anti-neoplastic agents described herein.

[0205] Cancer Gene Therapy and Cell Therapy In various embodiments, the agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with cancer gene therapy and cell therapy, including insertion of normal genes into cancer cells to replace mutated or altered genes; genetic modifications to silence mutated genes; genetic approaches to directly kill cancer cells; infusion of immune cells designed to enhance the immune response against cancer cells or to activate the patient's own immune system (T cells or natural killer cells) to kill cancer cells or to replace a large portion of the patient's own immune system to find and kill cancer cells; genetic approaches to modify cell activity to further alter endogenous immune responsiveness against cancer.

[0206] cell therapy In various embodiments, the agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with one or more cell therapies. Exemplary cell therapies include, but are not limited to, the co-administration of one or more populations of immune cells. In some embodiments, the immune cells are natural killer (NK) cells, NK-T cells, T cells, gamma delta T cells, B cells, cytokine-induced killer (CIK) cells, macrophage (MAC) cells, tumor infiltrating lymphocytes (TIL), granulocytes, innate lymphoid cells, megakaryocytes, monocytes, macrophages, platelets, thymocytes, myeloid cells, and / or dendritic cells (DCs). In some embodiments, the cell therapy involves the co-administration of a population of T cell therapy, e.g., alpha / beta TCR T cells, gamma / delta TCR T cells, regulatory T (Treg) cells, and / or TRuC™ T cells. In some embodiments, the cell therapy involves the co-administration of NK cell therapy, e.g., NK-92 or JK500 cells. Optionally, the cell therapy can involve the co-administration of cells that are autologous, syngeneic, or allogeneic to the subject.

[0207] In some embodiments, the cell therapy involves the co-administration of immune cells engineered to express a chimeric antigen receptor (CAR) or a T cell receptor (TCR). In certain embodiments, the population of immune cells is engineered to express a CAR, where the CAR comprises a tumor antigen binding domain. In other embodiments, the population of immune cells is engineered to express a T cell receptor (TCR) that is engineered to target a tumor-derived peptide displayed on the surface of a tumor cell. In one embodiment, the immune cells engineered to express a chimeric antigen receptor (CAR) or a T cell receptor (TCR) are T cells. In another embodiment, the immune cells engineered to express a chimeric antigen receptor (CAR) or a T cell receptor (TCR) are NK cells.

[0208] With regard to the structure of the CAR, in some embodiments, the CAR comprises an antigen binding domain, a transmembrane domain, and an intracellular signaling domain. In some embodiments, the intracellular domain comprises a primary signaling domain, a costimulatory domain, or both a primary signaling domain and a costimulatory domain. In certain embodiments, the primary signaling domain is selected from the group consisting of CD3 zeta, CD3 gamma, CD3 delta, CD3 epsilon, common FcR gamma (FCERIG), FcR beta (Fc Epsilon Rlb), CD79a, CD79b, Fc gamma RIIa, DAP10, and DAP12, 4-1BB / CD137, activating NK cell receptor, immunoglobulin protein, B7-H3, BAFFR, BLAME (SLAMF8), BTLA, CD100 (SEMA4D), CD103, CD160 (BY55), CD18, CD19, CD19a, CD2, CD247, CD27, CD276 (B7-H3), CD28, CD29, CD3 delta, CD3 epsilon, CD3 gamma, CD30, CD4, CD40, CD49a, CD49D, CD49f, CD69, CD7, CD84, CD8 alpha, CD8 beta, CD96 (Tactile), CD11a, CD11b, CD11c, CD11d, CDS, CEACAM1, CRT AM, cytokine receptor, DAP-10, DNAM1 (CD226), Fc gamma receptor, GADS, GITR, HVEM (LIGHTR), IA4, ICAM-1, ICAM-1, Ig alpha (CD79a), IL-2R beta, IL-2R gamma, IL-7R alpha, inducible T cell costimulator (ICOS), integrin, ITGA4, ITGA4, ITGA6, ITGAD, ITGAE, ITGAL, ITGAM, ITGAX, ITGB2, ITGB7, ITGB1, KIRDS2, LAT, LFA-1, ligand binding to CD83, LIGHT, LIGHT, LTBR, ​​Ly9 (CD229), Ly108), lymphocyte function-associated antigen-1 (LFA-1;and / or a functional signaling domain of one or more proteins selected from CD1-1a / CD18), MHC class 1 molecule, NKG2C, NKG2D, NKp30, NKp44, NKp46, NKp80 (KLRF1), OX-40, PAG / Cbp, programmed death-1 (PD-1), PSGL1, SELPLG (CD162), signaling lymphocyte activation molecule (SLAM protein), SLAM (SLAMF1, CD150; IPO-3), SLAMF4 (CD244, 2B4), SLAMF6 (NTB-A, SLAMF7, SLP-76, TNF receptor protein, TNFR2, TNFSF14, Toll ligand receptor, TRANCE / RANKL, VLA1, or VLA-6, or fragments, truncations, or combinations thereof;

[0209] In some embodiments, the costimulatory domain is selected from the group consisting of CD27, CD28, 4-1BB (CD137), OX40, CD30, CD40, PD-1, ICOS, CD2, CD7, LIGHT, NKG2C, lymphocyte function-associated antigen-1 (LFA-1), MYD88, B7-H3, a ligand that specifically binds CD83, CDS, ICAM-1, GITR, BAFFR, HVEM (LIGHTR), SLAMF7, NKp80 ( KLRFI), CD19, CD4, CD8 alpha, CD8 beta, IL2R beta, IL2R gamma, IL7R alpha, ITGA4, VLA1, CD49a, ITGA4, IA4, CD49D, ITGA6, VLA-6, CD49f, ITGAD, ITGAE, CD103, ITGAL, CD1A (NCBI gene ID: 909), CD1B (NCBI gene ID: 910), CD1C (NCBI gene ID: 91 1), CD1D (NCBI gene ID: 912), CD1E (NCBI gene ID: 913), ITGAM, ITGAX, ITGB1, CD29, ITGB2 (CD18, LFA-1), ITGB7, TNFR2, TRANCE / RANKL, DNAM1 (CD226), SLAMF4 (CD244, 2B4), CD84, CD96 (Tactile), CEACAM1, CRTAM, Ly9 (CD229), CD16 The present invention comprises a functional domain of one or more proteins selected from the group consisting of 0 (BY55), PSGL1, CD100 (SEMA4D), CD69, SLAMF6 (NTB-A, Ly108), SLAM (SLAMF1, CD150, IPO-3), BLAME (SLAMF8), SELPLG (CD162), LTBR, ​​LAT, GADS, SLP-76, PAG / Cbp, NKp44, NKp30, NKp46 and NKG2D.

[0210] In some embodiments, the transmembrane domain is selected from the group consisting of the alpha, beta, or zeta chain of the T cell receptor, CD28, CD3 epsilon, CD3 delta, CD3 gamma, CD45, CD4, CD5, CD7, CD8 alpha, CD8 beta, CD9, CD11a, CD11b, CD11c, CD11d, CD16, CD18, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137, CD154, KIRDS2, OX40, CD2, CD27, ICOS (CD278), 4-1BB (CD137), GITR, CD40, BAFFR, HVEM (LIGHTR), SLAMF7, NKp80 (KLRF1), CD19, CD19a, IL2R beta, IL2R gamma, IL7R alpha, ITGA1, VLA1, CD49a, ITGA4, IA4, CD49D, ITGA6, VLA-6, CD49f, ITGAD, CD1A, CD1B, CD1C, CD1D, CD1E, ITGAE, CD103, ITGAL, ITGAM, ITGAX, ITGB1, ITGB2, ITGB7, CD29, ITGB2 (LFA-1, CD18 ), ITGB7, TNFR2, DNAM1(CD226), SLAMF4(CD244, 2B4), CD84, CD96(TACTILE), CEACAM1, CRTAM, Ly9(CD229), CD160(BY55), PSGL1, CD100(SEMA4) D), SLAMF6 (NTB-A, Ly108), SLAM (SLAMF1, CD150, IPO-3), BLAME (SLAMF8), SELPLG (CD162), LTBR, ​​PAG / Cbp, NKp44, NKp30, NKp46, NKG2D, NKG2C The antibody comprises a transmembrane domain derived from a protein selected from an activating NK cell receptor, an immunoglobulin protein, BTLA, CD247, CD276 (B7-H3), CD30, CD84, CDS, a cytokine receptor, an Fc gamma receptor, GADS, ICAM-1, Ig alpha (CD79a), an integrin, LAT, a ligand that binds CD83, LIGHT, an MHC class 1 molecule, PAG / Cbp, TNFSF14, a Toll ligand receptor, TRANCE / RANKL, or a fragment, truncation, or combination thereof.

[0211] In some embodiments, the CAR comprises a hinge domain. The hinge domain is selected from the group consisting of CD2, CD3 delta, CD3 epsilon, CD3 gamma, CD4, CD7, CD8 alpha, CD8 beta, CD11a (ITGAL), CD11b (ITGAM), CD11c (ITGAX), CD11d (ITGAD), CD18 (ITGB2), CD19 (B4), CD27 (TNFRSF7), CD28, CD28T, CD29 (ITGB1), CD30 (TNFRSF8), CD40 (TNFRSF5), CD48 (SLAMF2), CD49a (ITGA1), CD49d (ITGA4), CD49f ( ITGA6), CD66a (CEACAM1), CD66b (CEACAM8), CD66c (CEACAM6), CD66d (CEACAM3), CD66e (CEACAM5), CD69 (CLEC2), CD79A (B cell antigen receptor complex-associated alpha chain), CD79B (B cell antigen receptor complex-associated beta chain), CD84 (SLAMF5), CD96 (Tactile), CD100 (SEMA4D), CD103 (ITGAE), CD134 (OX40), CD137 (4-1BB), CD150 (SLAMF1), CD15 8A(KIR2DL1), CD158B1(KIR2DL2), CD158B2(KIR2DL3), CD158C(KIR3DP1), CD158D(KIRDL4), CD158F1(KIR2DL5A), CD158F2(KIR2DL5B), CD158K(K IR3DL2), CD160(BY55), CD162(SELPLG), CD226(DNAM1), CD229(SLAMF3), CD244(SLAMF4), CD247(CD3-Zeta), CD258(LIGHT), CD268(BAFFR), CD270 (TNFSF14), CD272(BTLA), CD276(B7-H3), CD279(PD-1), CD314(NKG2D), CD319(SLAMF7), CD335(NK-p46), CD336(NK-p44), CD337(NK-p30), CD352 (SLAMF6), CD353 (SLAMF8), CD355 (CRTAM), CD357 (TNFRSF18), inducible T cell costimulatory factor (ICOS), LFA-1 (CD11a / CD18), NKG2C, DAP-10, ICAM-1, NKp80 (KLRF1),The antibody may be derived from a protein selected from IL-2R beta, IL-2R gamma, IL-7R alpha, LFA-1, SLAMF9, LAT, GADS (GrpL), SLP-76 (LCP2), PAG1 / CBP, CD83 ligand, Fc gamma receptor, MHC class 1 molecule, MHC class 2 molecule, TNF receptor protein, immunoglobulin protein, cytokine receptor, integrin, activating NK cell receptor, or Toll ligand receptor, IgG1, IgG2, IgG3, IgG4, IgA, IgD, IgE, IgM, or a fragment or combination thereof.

[0212] In some embodiments, the TCR or CAR antigen binding domain or immunotherapeutic agent (e.g., a monospecific or multispecific antibody or antigen-binding fragment thereof or an antibody mimetic) described herein binds to a tumor-associated antigen (TAA). In some embodiments, the tumor associated antigen is CD19; CD123; CD22; CD30; CD171; CS-1 (CD2 subset 1, also referred to as CRACC, SLAMF7, CD319, and 19A24); C-type lectin-like molecule-1 (CLL-1 or CLECLI); CD33; epidermal growth factor receptor variant III (EGFRvlll); ganglioside G2 (GD2); ganglioside GD3 (αNeuSAc(2-8)αNeuSAc(2-3)βDGaip(1-4)bDGIcp(1-1)Cer); ganglioside GM3 (αNeuSAc(2-3)βDGalp(1-4)βDGlcp(1-1)Cer); GM-CSF receptor; TNF receptor superfamily member 17 (TNFRSF17, BCMA); B-lymphocyte cell adhesion molecule; Tn antigen ((Tn Ag) or (GaINAcu-Ser / Thr)); prostate-specific membrane antigen (PSMA); receptor tyrosine kinase-like orphan receptor 1 (RORI); tumor-associated glycoprotein 72 (TAG72); CD38; CD44v6; carcinoembryonic antigen (CEA); epithelial cell adhesion molecule (EPCAM); B7H3 (CD276); KIT (CD117); interleukin-13 receptor subunit alpha-2 (IL-13Ra2 or CD213A2); mesothelin; interleukin-11 receptor alpha (IL-11Ra); prostate stem cell antigen (PSCA); protease inhibitor phospho-21 (testisin or PRSS21); vascular endothelial growth factor receptor 2 (VEGFR2); HLA class I antigen A-2 alpha; HLA antigen; Lewis (Y) antigen; CD24; platelet-derived growth factor receptor beta (PDGFR-beta); stage-specific embryonic antigen-4 (SSEA-4); CD20; delta-like 3 (DLL3); folate receptor alpha; folate receptor beta, GDNF alpha 4 receptor, receptor tyrosine protein kinase, ERBB2 (Her2 / neu); mucin 1, cell surface associated (MUC1); APRIL receptor; ADP-ribosyl cyclase-1;Ephb4 tyrosine kinase receptor, DCAMKL1 serine threonine kinase, aspartate beta-hydroxylase, epidermal growth factor receptor (EGFR); neural cell adhesion molecule (NCAM); prostase; prostatic acid phosphatase (PAP); elongation factor 2 mutated (ELF2M); ephrin B2; fibroblast activation protein alpha (FAP); insulin-like growth factor 1 receptor (IGF-I receptor), carbonic anhydrase IX (CAIX); proteasome (prosome, macropheoin) LMP2, subunit, beta type, 9 (LMP2); glycoprotein 100 (gp100); oncogene fusion protein consisting of breakpoint cluster region (BCR) and Abelson murine leukemia viral oncogene homolog 1 (abl) (bcr-abl); tyrosinase; ephrin type A receptor 2 (EphA2); ephrin type A receptor 3 (EphA3), fucosyl-GM1; sialyl Lewis adhesion molecule (sLe); transglutaminase 5 (TGS5); high molecular weight melanoma-associated antigen (HMWMAA); o-acetyl-GD2 ganglioside (OAcGD2); folate receptor beta; tumor endothelial marker 1 (TEM1 / CD248); tumor endothelial marker 7-related (TEM7R); six transmembrane epithelial antigen of prostate I (STEAP1); claudin 6 (CLDN6); thyroid-stimulating hormone receptor (TSHR); G protein-coupled receptor class C group 5 member D (GPRCSD); IL-15 receptor (IL-15); X chromosome open reading frame 61 (CXORF61); CD97 ;CD179a;anaplastic lymphoma kinase (ALK);polysialic acid;placenta specific 1 (PLAC1);hexasaccharide moiety of globoH glycoceramide (GloboH);mammary differentiation antigen (NY-BR-1);uroplakin 2 (UPK2);hepatitis A virus cell receptor 1 (HAVCR1);adrenergic receptor beta 3 (ADRB3);pannexin 3 (PANX3);G protein-coupled receptor 20 (GPR20);lymphocyte antigen 6 complex, locus K9 (LY6K);olfactory receptor 51E2 (ORS IE2);TCR gamma alternative reading frame protein (TARP);Wilms tumor protein (WT1);cancer / testis antigen 1 (NY-ESO-1);cancer / testis antigen 2 (LAGE-la);melanoma-associated antigen 1 (MAGE-A1);melanoma-associated antigen 3 (MAGE-A3);melanoma-associated antigen 4 (MAGE-A4); T-cell receptor beta 2 chain C; ETS translocation variant gene 6 located on chromosome 12p (ETV6-AML); sperm protein 17 (SPA17); X antigen family, member 1A (XAGE1); angiopoietin-binding cell surface receptor 2 (Tie2); melanoma cancer testis antigen-1 (MADCT-1); melanoma cancer testis antigen-2 (MAD-CT-2); Fos-related antigen 1; tumor protein p53 (p53); p53 mutant; prostein; survivin; telomerase; prostate cancer tumor antigen-1 (PCTA-1 or galectin 8), melanoma antigen 1 recognized by T cells (MelanA or MARTI); rat sarcoma (Ras) mutant; human telomerase reverse transcriptase (hTERT); sarcoma translocation breakpoints; melanoma inhibitor of apoptosis (ML-IAP); ERG (transmembrane protease, serine 2 (TMPRSS2) ETS fusion gene); N-acetylglucosaminyltransferase V (NA17); paired box protein Pax-3 (PAX3); androgen receptor; cyclin-A1; cyclin B1; v-myc avian myeloma viral oncogene neuroblastoma-derived homolog (MYCN); Ras homolog family member C (RhoC); tyrosinase-related protein 2 (TRP-2); cytochrome P450 1B1 (CYP IBI); CCCTC-binding agent (zinc finger protein)-like (BORIS or Brother of the Regulator of Imprinted Sites), squamous cell carcinoma antigen 3 recognized by T cells (SART3); paired box protein Pax-5 (PAX5); proacrosin-binding protein sp32 (OY-TES I); lymphocyte-specific protein tyrosine kinase (LCK); A-kinase anchoring protein 4 (AKAP-4); peptidoglycan recognition protein, synovial sarcoma, X-breakpoint 2 (SSX2); receptor for advanced glycation end products (RAGE-I); renal ubiquitous 1 (RUI); renal ubiquitous 2 (RU2); legumain; human papillomavirus E6 (HPV E6); human papillomavirus E7 (HPV E7); intestinal carboxylesterase; heat shock protein 70-2 mutant (mut hsp70-2);CD79a;CD79b;CD72;leukocyte-associated immunoglobulin-like receptor 1 (LAIRI);The target is selected from Fc fragment of IgA receptor (FCAR or CD89); leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2); CD300 molecule-like family member f (CD300LF); C-type lectin domain family 12 member A (CLEC12A); bone marrow stromal cell antigen 2 (BST2); EGF-like module-containing mucin-like hormone receptor-like 2 (EMR2); lymphocyte antigen 75 (LY75); glypican-2 (GPC2); glypican-3 (GPC3); Fc receptor-like 5 (FCRL5); and immunoglobulin lambda-like polypeptide 1 (IGLL1). In some embodiments, the target is an epitope of a tumor-associated antigen that is presented on MHC.;

[0213] In some embodiments, the tumor antigen is CD150, 5T4, ActRIIA, B7, TNF receptor superfamily member 17 (TNFRSF17, BCMA), CA-125, CCNA1, CD123, CD126, CD138, CD14, CD148, CD15, CD19, CD20, CD200, CD21, CD22, CD23, CD24, CD25, CD26, CD261, CD262, CD30, CD33, CD362, CD37, CD38, CD4, CD40, CD40L, CD44, CD46, CD5, C D52, CD53, CD54, CD56, CD66a-d, CD74, CD8, CD80, CD92, CE7, CS-1, CSPG4, ED-B Fibronectin, EGFR, EGFRvIII, EGP-2, EGP-4, EPHa2, ErbB2, ErbB3, ErbB4, FBP, HER1-HER2 combination, HER2-HER3 combination, HERV-K, HIV-1 envelope glycoprotein gp120, HIV-1 envelope glycoprotein gp41, HLA-DR, HLA class I antigen alpha G, HM1.24, K-Ras GTPase, HMW-MAA, Her2, Her2 / neu, IGF-1R, IL-11Ralpha, IL-13R-alpha2, IL-2, IL-22R-alpha, IL-6, IL-6R, Ia, Ii, L1-CAM, L1-cell adhesion molecule, Lewis Y, Ll-CAM, MAGE A3, MAGE-A1, MART-1, MUC1, NKG2C ligand, NKG2D ligand, NYESO-1, OEPHa2, PIGF, PSCA, PSMA, ROR1, T101, TAC, TAG72, TIM-3, TRAIL R1, TRAIL R1 (DR4), TRAIL-R2 (DR5), VEGF, VEGFR2, WT-I, G protein-coupled receptor, alpha-fetoprotein (AFP), angiogenic agent, exogenous cognate binding molecule (ExoCBM), oncogene product, antifolate receptor, c-Met, carcinoembryonic antigen (CEA), cyclin (D1), ephrin B2, epithelial tumor antigen, estrogen receptor, fetal acetylcholine e receptor, folate binding protein, gp100, hepatitis B surface antigen, Epstein-Barr nuclear antigen 1 , latent membrane protein 1, secreted protein BARF1, P2X7 purinergic receptor, syndecan-1, kappa chain, kappa light chain, kdr, lambda chain, livin, melanoma associated antigen, mesothelin, mouse double minute 2 homolog (MDM2), mucin 16 (MUC16), mutant p53, mutant ras, necrosis antigen, carcinoembryonic antigen, ROR2, progesterone receptor, prostate specific antigen, tEGFR, tenascin, P2-microglobulin, Fc receptor-like 5 (FcRL5).

[0214] Examples of cell therapies include AMG-119, Algenpantucel-L, ALOFISEL (registered trademark), Sipuleucel-T, (BPX-501) rivogenlecleucel, U.S. Patent Application Publication No. 9,089,520, International Publication No. 2016 / 100236, AU-105, ACTR-087, activated allogeneic natural killer cells CNDO-109-AANK, MG-4101, AU-101, BPX-601, FATE-NK100, LFU-835 hematopoietic stem cells, Imilecleucel-T, baltaleucel-T, PNK-007, UCARTCS1, ET-1504, ET-1501, ET-1502, ET-190, CD19-ARTEMIS, ProHema, FT-1050 bone marrow stem cell therapy by treatment, CD4CARNK-92 cells, SNK-01, NEXI-001, CryoStim, AlloStim, lentiviral transduction of huCART-meso cells, CART-22 cells, EGFRt / 19-28z / 4-1BBL CAR T cells, autologous 4H11-28z / fIL-12 / EFGRt T cells, CCR5-SBC-728-HSPC, CAR4-1BBZ, CH-296, dnTGFbRII-NY-ESOc259T, Ad-RTS-IL-12, IMA-101, IMA-201, CARMA-0508, TT-18, CMD-501, CMD-503, CMD-504, CMD-502, CMD-601, CMD-602, CSG-005, LAAP T cell therapy, PD-1 knockout T cell therapy (esophageal cancer / NSCLC), anti-MUC1 CAR T cell therapy (esophageal cancer / NSCLC), anti-MUC1 CAR T cell therapy + PD-1 knockout T cell therapy (esophageal cancer / NSCLC), anti-KRAS G12D mTCR PBL, anti-CD123 CAR T cell therapy, anti-mutated neoantigen TCR T cell therapy, tumor lysate / MUC1 / survivin PepTivator-loaded dendritic cell vaccine, autologous dendritic cell vaccine (metastatic malignant melanoma, intradermal / intravenous), anti-LeY-scFv-CD28-zeta CAR T cells, PRGN-3005, iC9-GD2-CAR-IL-15T-cells, HSC-100, ATL-DC-101, MIDRIX4-LUNG, MIDRIXNEO, FCR-001, PLX stem cell therapy, MDR-101, GeniusVac-Mel4, ilixadencel, allogeneic mesenchymal stem cell therapy, romyelocel L, CYNK-001, ProTrans, ECT-100, MSCTRAIL, dilanubicel, FT-516, ASTVAC-2, E-CEL These include, but are not limited to, UVEC, CK-0801, allogeneic alpha / beta CD3+ T cell and CD19+ B cell depleted stem cells (hematological disorders, TBX-1400, HLCN-061, umbilical cord derived Hu-PHEC cells (hematological malignancies / aplastic anemia), AP-011, apceth-201, apceth-301, SENTI-101, stem cell therapy (pancreatic cancer), ICOVIR15-cBiTE, CD33HSC / CD33 CAR-T, PLX-Immune, SUBCUVAX, CRISPR allogeneic gamma-delta T cell based gene therapy (cancer), ex vivo CRISPR allogeneic healthy donor NK cell based gene therapy (cancer), ex vivo allogeneic induced pluripotent stem cell-derived NK cell based gene therapy (solid tumors), and anti-CD20 CAR T cell therapy (non-Hodgkin's lymphoma).

[0215] Additional agents for targeting tumors Additional agents for targeting tumors include alpha-fetoprotein modulating agents such as ET-1402, and AFP-TCR; anthrax toxin receptor 1 modulators, e.g., anti-TEM8 CAR T cell therapy; TNF receptor superfamily member 17 (TNFRSF17, BCMA), such as bb-2121 (ide-cel), bb-21217, JCARH125, UCART-BCMA, ET-140, MCM-998, LCAR-B38M, CART-BCMA, SEA-BCMA, BB212, ET-140, P-BCMA-101, AUTO-2 (APRIL-CAR), JNJ-68284528; anti-CLL-1 antibodies (see, e.g., International Application No. PCT / US2017 / 025573); anti-PD-L1-CAR tank cell therapy, such as KD-045; anti-PD-L1 t-haNK, e.g., PD-L1 t-haNK; anti-CD45 antibodies, such as 131I-BC8 (lomab-B); anti-HER3 antibodies, such as LJM716, GSK2849330; APRIL receptor modulators, such as anti-BCMA CAR T cell therapy, Descartes-011; ADP-ribosyl cyclase-1 / APRIL receptor modulators, such as anti-BCMA / anti-CD38 dual CAR T cell therapy; CART-ddBCMA; B7 homolog 6, such as CAR-NKp30 and CAR-B7H6;B lymphocyte antigen CD19, e.g., TBI-1501, CTL-119 huCART-19 T cells, liso-cel, JCAR-015 U.S. Pat. No. 7,446,190, JCAR-014, JCAR-017 (WO 2016196388, WO 2016033570, WO 2015157386), axicabtageneciloreucel (KTE-C19, Yescarta®), KTE-X19, U.S. Pat. No. 7,741,465, WO 6,319,494, UCART-19, EBV-CTL, Ttisagenlecleucel-T (CTL019), WO 2012079000, WO 2017049166, CD19CAR-CD28-CD3zeta-EGFRt expressing T cells, CD19 / 4-1BBL armed CAR T cell therapy, C-CAR-011, CIK-CAR.CD19, CD19CAR-28-zeta T cell, PCAR-019, MatchCART, DSCAR-01, IM19 CAR-T, TC-110; Anti-CD19 CAR T-cell therapy (B-cell acute lymphoblastic leukemia, National University of Malaysia); Anti-CD19 CAR T cell therapy (acute lymphoblastic leukemia / non-Hodgkin's lymphoma, Heidelberg University Hospital), anti-CD19 CAR T cell therapy (IL-6 expression suppression, cancer, Shanghai Unicar-Therapy Bio-medicine) Technology), MB-CART2019.1 (CD19 / CD20), GC-197 (CD19 / CD7), CLIC-1901, ET-019003, anti-CD19-STAR-T cells, AVA-001, BCMA-CD19 cCAR(CD19 / APRIL), ICG-134, ICG-132(CD19 / CD20), CTA-101, WZTL-002, anti-CD19 / anti-CD20 dual CAR T cells (chronic lymphocytic leukemia / B cell lymphoma), HY-001, ET-019002, YTB-323, GC-012(CD19 / APRIL), GC-022(CD19 / CD22), CD19CAR-CD28-CD3 zeta-EGFRt expressing Tn / mem; allogeneic anti-CD19 CAR T cells such as UCAR-011, ICTCAR-014, GC-007F, PTG-01, CC-97540; GC-007G; APRIL receptor modulators;SLAM family member 7 modulators, BCMA-CS1 cCAR; autologous dendritic cell tumor antigens (ADCTA), such as ADCTA-SSI-G; B-lymphocyte antigen CD20, e.g., ACTR707 ATTCK-20, PBCAR-20A; allogeneic T cells expressing CD20 CARs, such as LB-1905; B-lymphocyte antigen CD19 / B-lymphocyte antigen 22, e.g., TC-310; B-lymphocyte antigen 22 cell adhesion, e.g., UCART-22, JCAR-018 International Publication No. WO2016090190; NY-ESO-1 modulators, e.g., GSK-3377794, TBI-1301, GSK3537142; carbonic anhydrase, e.g., DC-Ad-GMCAIX; caspase 9 suicide genes, e.g., CaspaCIDe DLI, BPX-501; CCR5, e.g., SB-728; CCR5 gene inhibitor / TAT gene / TRIM5 gene stimulator, e.g., CCR5 shRNA / TRIM5 alpha / TAR decoy lentiviral vector transduced autologous CD34 positive hematopoietic progenitor cells; CDw123, e.g., MB-102, IM-23, JEZ-567, UCART-123; CD4, e.g., ICG-122; CD5 modulator, e.g., CD5.28z CART cells; anti-CD22, e.g., anti-CD22 CART; anti-CD30, e.g., TT-11; dual anti-CD33 / anti-CLL, such as LB-1910 1;CD40 ligand, e.g., BPX-201, MEDI5083;CD56, e.g., allogeneic CD56 positive CD3 negative natural killer cells (myeloid malignancies);CD19 / CD7 modulators, e.g., GC-197;T cell antigen CD7 modulators, e.g., anti-CD7 CAR T cell therapy (CD7 positive hematologic malignancies);CD123 modulators, e.g., UniCAR02-T-CD123;anti-CD276, e.g., anti-CD276 CART;CEACAM protein 5 modulators, e.g., MG7-CART;Claudin 6, e.g., CSG-002;Claudin 18.2, e.g., LB-1904;Chlorotoxin, e.g., CLTX-CART;EBV targeting, e.g., CMD-003;MUC16EGFR, e.g., autologous 4H11-28z / fIL-12 / EFGRt T cells; endonucleases, e.g., PGN-514, PGN-201;Epstein-Barr virus specific T lymphocytes, e.g., TT-10; Epstein-Barr nuclear antigen 1 / latent membrane protein 1 / secreted protein BARF1 modulators, e.g., TT-10X; Erbb2, e.g., CST-102, CIDeCAR; Ganglioside (GD2), e.g., 4SCAR-GD2; Gamma delta T cells, e.g., ICS-200; Folate hydrolase 1 (FOLH1, glutamic acid carboxypeptidase II, PSMA; NCBI Gene ID: 2346), e.g., CIK-CAR.PSMA, CART-PSMA-TGFβRDN, P-PSMA-101; Glypican-3 (GPC3), e.g., TT-16, GLYCAR; Hemoglobin, e.g., PGN-236; Hepatocyte growth factor receptor, e.g., anti-cMet RNA CAR T; HLA class I antigen A-2 alpha modulators, e.g., FH-MCVA2TCR; HLA class I antigen A-2 alpha / melanoma associated antigen 4 modulators, e.g., ADP-A2M4CD8; HLA antigen modulators, e.g., FIT-001, NeoTCR-P1; human papillomavirus E7 proteins such as KITE-439 (see, e.g., International Application No. PCT / US2015 / 033129); ICAM-1 modulators, e.g., AIC-100; immunoglobulin gamma Fc receptor III, e.g., ACTR087; IL-12, e.g., DC-RTS-I L-12; IL-12 agonist / mucin 16, e.g., JCAR-020; IL-13 alpha 2, e.g., MB-101; IL-15 receptor agonists such as PRGN-3006, ALT-803; interleukin-15 / Fc fusion proteins (e.g., XmAb24306), recombinant interleukin-15 (e.g., AM0015, NIZ-985), pegylated IL-15 (e.g., NKTR-255); IL-2, e.g., CST-101; interferon alpha ligands, e.g., autologous tumor cell vaccine + systemic CpG-B + IFN-alpha (cancer); K-Ras GTPases, e.g., anti-KRAS G12V mTCR cell therapy; neural cell adhesion molecule L1 L1CAM (CD171), e.g., JCAR-023; latent membrane protein 1 / latent membrane protein 2, e.g., Ad5f35-LMPd1-2 transduced autologous dendritic cells;MART-1 melanoma antigen modulators, e.g., MART-1 F5 TCR engineered PBMC; melanoma associated antigen 10, e.g., MAGE-A10C796T MAGE-A10 TCR; melanoma associated antigen 3 / melanoma associated antigen 6 (MAGE A3 / A6) such as KITE-718 (see, e.g., International Application PCT / US2013 / 059608); mesothelin, e.g., CSG-MESO, TC-210; mucin 1 modulators, e.g., ICTCAR-052, Tn MUC-1 CAR-T, ICTCAR-053; anti-MICA / MICB, e.g., CYAD-02; NKG2D, e.g., NKR-2; Ntrkr1 tyrosine kinase receptor, e.g., JCAR-024; PRAMET cell receptor, e.g., BPX-701; prostate stem cell antigen modulators, e.g., MB-105; roundabout homolog 1 modulators, e.g., ATCG-427; peptidoglycan recognition protein modulators, e.g., Tag-7 genetically modified autologous tumor cell vaccines; PSMA-CAR T cell therapy (PSMA, e.g., lentiviral vectors, castration-resistant prostate cancer); SLAM family member 7 modulators, e.g., IC9-Luc90-CD828Z; TGF beta receptor modulators, e.g., DNR.NPC These include, but are not limited to, T cells; T lymphocytes, e.g., TT-12; T lymphocyte stimulators, e.g., ATL-001; TSH receptor modulators, e.g., ICTCAR-051; tumor infiltrating lymphocytes, such as LN-144, LN-145; and / or Wilms tumor proteins, such as JTCR-016, WT1-CTL, ASP-7517;

[0216] MCL1 Apoptosis Regulator, BCL2 Family Member (MCL1) Inhibitor In various embodiments, the anti-CD47 or anti-SIRPα agents described herein are combined with an inhibitor of MCL1 apoptosis regulator, BCL2 family member (MCL1, TM; EAT; MCL1L; MCL1S; Mcl-1; BCL2L3; MCL1-ES; bcl2-L-3; mcl1 / EAT; NCBI gene ID: 4170). Examples of MCL1 inhibitors include AMG-176, AMG-397, S-64315, and AZD-5991, 483-LM, A-1210477, UMI-77, JKY-5-037, and those described in WO2018183418, WO2016033486, WO2019222112, and WO2017147410.

[0217] Cytokine-induced SH2-containing protein (CISH) inhibitors In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with inhibitors of cytokine-inducible SH2-containing proteins (CISH; CIS; G18; SOCS; CIS-1; BACTS2; NCBI Gene ID: 1154). Examples of CISH inhibitors include those described in WO2017100861, WO2018075664, and WO2019213610.

[0218] Gene Editor In various embodiments, agents that inhibit binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are further combined with a gene editor. Exemplary gene editing systems that may be co-administered include, but are not limited to, CRISPR / Cas9 systems, zinc finger nuclease systems, TALEN systems, homing endonuclease systems (e.g., ARCUS), and homing meganuclease systems.

[0219] Other drugs with unspecified targets In various embodiments, the agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are administered in the form of human immunoglobulin (10% liquid formulation), Cuvitru (human immunoglobulin (20% solution), levofolinate disodium, IMSA-101, BMS-986288, IMUNO BGC Moreau Further combined with RJ, R-OKY-034F, GP-2250, AR-23, calcium levofolinate, porfimer sodium, RG6160, ABBV-155, CC-99282, polifeprozan 20 with carmustine, Veregen, gadoxetate disodium, gadobutrol, gadoterate meglumine, gadoteridol, 99mTc-sestamibi, pomalidomide, pacibanil, and / or valrubicin.

[0220] Exemplary Combination Therapies In various embodiments, an agent that inhibits the binding between CD47 and SIRPα (e.g., magrolimab) and an anti-Trop-2 ADC (e.g., sacituzumab govitecan) described herein are further combined with a standard of care regimen for treating Trop-2 positive solid tumors.

[0221] Breast Cancer Combination Therapy Therapeutic agents used to treat breast cancer include albumin-bound paclitaxel, anastrozole, atezolizumab, capecitabine, carboplatin, cisplatin, cyclophosphamide, docetaxel, doxorubicin, epirubicin, everolimus, exemestane, fluorouracil, fulvestrant, gemcitabine, ixabepilone, lapatinib, letrozole, methotrexate, mitoxantrone, paclitaxel, pegylated liposomal doxorubicin, pertuzumab, tamoxifen, toremifene, trastuzumab, vinorelbine, and any combination thereof. In some embodiments, therapeutic agents used to treat breast cancer (e.g., HR+ / - / HER2+ / -) include trastuzumab (HERCEPTIN®), pertuzumab (PERJETA®), docetaxel, carboplatin, palbociclib (IBRANCE®), letrozole, trastuzumab emtansine (KADCYLA®), fulvestrant (FASLODEX®), olaparib (LYNPARZA®), eribulin, tucatinib, capecitabine, lapatinib, everolimus (AFINITOR®), exemestane, eribulin mesylate (HALAVEN®), and combinations thereof. In some embodiments, the therapeutic agents used to treat breast cancer include trastuzumab + pertuzumab + docetaxel, trastuzumab + pertuzumab + docetaxel + carboplatin, palbociclib + letrozole, tucatinib + capecitabine, lapatinib + capecitabine, palbociclib + fulvestrant, or everolimus + exemestane. In some embodiments, the therapeutic agents used to treat breast cancer include trastuzumab deruxtecan (ENHERTU®), datopotamab deruxtecan (DS-1062), enfortumumab vedotin (PADCEV®), balixafortide, elacestrant, or combinations thereof. In some embodiments, the therapeutic agents used to treat breast cancer include balixafortide + eribulin.

[0222] Triple Negative Breast Cancer (TNBC) Combination Therapy Therapeutic agents used to treat TNBC include atezolizumab, cyclophosphamide, docetaxel, doxorubicin, epirubicin, fluorouracil, paclitaxel, and combinations thereof. In some embodiments, therapeutic agents used to treat TNBC include olaparib (LYNPARZA®), atezolizumab (TECENTRIQ®), paclitaxel or nab-paclitaxel (ABRAXANE®), eribulin, bevacizumab (AVASTIN®), carboplatin, gemcitabine, eribulin mesylate (HALAVEN®), pembrolizumab (KEYTRUDA®), cisplatin, doxorubicin, epirubicin, or combinations thereof. In some embodiments, therapeutic agents for treating TNBC include atezolizumab + paclitaxel, bevacizumab + paclitaxel, carboplatin + paclitaxel, carboplatin + gemcitabine, or paclitaxel + gemcitabine. In some embodiments, therapeutic agents used to treat TNBC include eliyaspase, capivasertib, alpelisib, rucaparib + nivolumab, atezolumab + paclitaxel + gemcitabine + capecitabine + carboplatin, ipatasertib + paclitaxel, radilatuzumab vedotin + pembrolimab, durvalumab + DS-8201a, trilaciclib + gemcitabine + carboplatin. In some embodiments, therapeutic agents used to treat TNBC include trastuzumab deruxtecan (ENHERTU®), datopotamab deruxtecan (DS-1062), enfortumab vedotin (PADCEV®), balixafortide, adagroxadocimorenin, neripepimto-s (NEUVAX®), nivolumab (OPDIVO®), rucaparib, toripalimab (TUOYI®), camrelizumab, capivasertib, durvalumab (IMFINZI®), and combinations thereof.In some embodiments, therapeutic agents used to treat TNBC include nivolumab + rucaparib, bevacizumab (AVASTIN®) + chemotherapy, toripalimab + paclitaxel, toripalimab + albumin-bound paclitaxel, camrelizumab + chemotherapy, pembrolizumab + chemotherapy, balixafortide + eribulin, durvalumab + trastuzumab deruxtecan, durvalumab + paclitaxel, or capivasertib + paclitaxel.

[0223] Bladder Cancer Combination Therapy Therapeutic agents used to treat bladder cancer include datopotamab deruxtecan (DS-1062), trastuzumab deruxtecan (ENHERTU®), erdafitinib, eganelisib, lenvatinib, bempegaldesleukin (NKTR-214), or combinations thereof. In some embodiments, therapeutic agents used to treat bladder cancer include eganelisib + nivolumab, pembrolizumab (KEYTRUDA®) + enfortumumab vedotin (PADCEV®), nivolumab + ipilimumab, duravalumab + tremelimumab, lenvatinib + pembrolizumab, enfortumumab vedotin (PADCEV®) + pembrolizumab, and bempegaldesleukin + nivolumab.

[0224] Colorectal cancer (CRC) combination therapy Therapeutic agents used to treat CRC include bevacizumab, capecitabine, cetuximab, fluorouracil, irinotecan, leucovorin, oxaliplatin, panitumumab, ziv-aflibercept, and any combination thereof. In some embodiments, therapeutic agents used to treat CRC include bevacizumab (AVASTIN®), leucovorin, 5-FU, oxaliplatin (FOLFOX), pembrolizumab (KEYTRUDA®), FOLFIRI, regorafenib (STIVARGA®), aflibercept (ZALTRAP®), cetuximab (ERBITUX®), Lonsurf (ORCANTAS®), XELOX, FOLFOXIRI, or combinations thereof. In some embodiments, therapeutic agents used to treat CRC include bevacizumab + leucovorin + 5-FU + oxaliplatin (FOLFOX), bevacizumab + FOLFIRI, bevacizumab + FOLFOX, aflibercept + FOLFIRI, cetuximab + FOLFIRI, bevacizumab + XELOX, and bevacizumab + FOLFOXIRI. In some embodiments, therapeutic agents used to treat CRC include binimetinib + encorafenib + cetuximab, trametinib + dabrafenib + panitumumab, trastuzumab + pertuzumab, napabucasin + FOLFIRI + bevacizumab, nivolumab + ipilimumab.

[0225] Combination therapy for esophageal and esophagogastric junction cancer Therapeutic agents used to treat esophageal and esophagogastric junction cancer include capecitabine, carboplatin, cisplatin, docetaxel, epirubicin, fluoropyrimidines, fluorouracil, irinotecan, leucovorin, oxaliplatin, paclitaxel, ramucirumab, trastuzumab, and any combination thereof. In some embodiments, therapeutic agents used to treat gastroesophageal junction cancer (GEJ) include herceptin, cisplatin, 5-FU, ramicurimab, or paclitaxel. In some embodiments, therapeutic agents used to treat GEJ cancer include ALX-148, AO-176, or IBI-188.

[0226] Gastric Cancer Combination Therapy Therapeutic agents used to treat gastric cancer include capecitabine, carboplatin, cisplatin, docetaxel, epirubicin, fluoropyrimidines, fluorouracil, irinotecan, leucovorin, mitomycin, oxaliplatin, paclitaxel, ramucirumab, trastuzumab, and any combination thereof.

[0227] Head and Neck Cancer Combination Therapy Therapeutic agents used to treat head and neck cancer include afatinib, bleomycin, capecitabine, carboplatin, cetuximab, cisplatin, docetaxel, fluorouracil, gemcitabine, hydroxyurea, methotrexate, nivolumab, paclitaxel, pembrolizumab, vinorelbine, and any combination thereof.

[0228] Therapeutic agents used to treat head and neck squamous cell carcinoma (HNSCC) include pembrolizumab, carboplatin, 5-FU, docetaxel, cetuximab (Erbitux®), cisplatin, nivolumab (OPDIVO®), and combinations thereof. In some embodiments, therapeutic agents used to treat HNSCC include pembrolizumab + carboplatin + 5-FU, cetuximab + cisplatin + 5-FU, cetuximab + carboplatin + 5-FU, cisplatin + 5-FU, and carboplatin + 5-FU. In some embodiments, therapeutic agents used to treat HNSCC include durvalumab, durvalumab + tremelimumab, nivolumab + ipilimumab, lovaleucel, pembrolizumab, pembrolizumab + epacadostat, GSK3359609 + pembrolizumab, lenvatinib + pembrolizumab, retifanlimab, retifanlimab + enobituzumab, ADU-S100 + pembrolizumab, epacadostat + nivolumab + ipilimumab / lirilumab.

[0229] Combination therapy for non-small cell lung cancer Therapeutic agents used to treat non-small cell lung cancer (NSCLC) include afatinib, albumin-bound paclitaxel, alectinib, atezolizumab, bevacizumab, cabozantinib, carboplatin, cisplatin, crizotinib, dabrafenib, docetaxel, erlotinib, etoposide, gemcitabine, nivolumab, paclitaxel, pembrolizumab, pemetrexed, ramucirumab, trametinib, trastuzumab, vandetanib, vemurafenib, vinblastine, vinorelbine, and any combination thereof. In some embodiments, therapeutic agents used to treat NSCLC include alectinib (ALECENSA®), dabrafenib (TAFINLAR®), trametinib (MEKINIST®), osimertinib (TAGRISSO®), entrectinib (TARCEVA®), crizotinib (XALKORI®), pembrolizumab (KEYTRUDA®), carboplatin (CTLAR®), rivaroxaban (RIRVOX ... These include cisplatin, pemetrexed (ALIMTA®), nab-paclitaxel (ABRAXANE®), ramucirumab (CYRAMZA®), docetaxel, bevacizumab (AVASTIN®), brigatinib, gemcitabine, cisplatin, afatinib (GILOTRIF®), nivolumab (OPDIVO®), gefitinib (IRESSA®), and combinations thereof. In some embodiments, the therapeutic agents used to treat NSCLC include dabrafenib + trametinib, pembrolizumab + carboplatin + pemetrexed, pembrolizumab + carboplatin + nab-paclitaxel, ramucirumab + docetaxel, bevacizumab + carboplatin + pemetrexed, pembrolizumab + pemetrexed + carboplatin, cisplatin + pemetrexed, bevacizumab + carboplatin + nab-paclitaxel, cisplatin + gemzar, nivolumab + docetaxel, carboplatin + pemetrexed, carboplatin + nab-paclitaxel, or pemetrexed + cisplatin + carboplatin.In some embodiments, therapeutic agents used for NSCLC include datopotamab deruxtecan (DS-1062), trastuzumab deruxtecan (ENHERTU®), enfortumab vedotin (PADCEV®), durvalumab, canakinumab, cemiplimab, nogapendekin alfa, avelumab, tiragolumab, donbanalimab, vibostolimab, osipellimab, or combinations thereof. In some embodiments, the therapeutic agents used to treat NSCLC include datopotamab deruxtecan + pembrolizumab, datopotamab deruxtecan + durvalumab, durvalumab + tremelimumab, pembrolizumab + lenvatinib + pemetrexed, pembrolizumab + olaparib, nogapendekin alfa (N-803) + pembrolizumab, tiragolumab + atezolizumab, vibostolimab + pembrolizumab, or osipellimab + tislelizumab.

[0230] Small cell lung cancer combination therapy Therapeutic agents used to treat small cell lung cancer (SCLC) include atezolizumab, bendamustime, carboplatin, cisplatin, cyclophosphamide, docetaxel, doxorubicin, etoposide, gemcitabine, ipilimumab, irinotecan, nivolumab, paclitaxel, temozolomide, topotecan, vincristine, vinorelbine, and any combination thereof. In some embodiments, therapeutic agents used to treat SCLC include atezolizumab, carboplatin, cisplatin, etoposide, paclitaxel, topotecan, nivolumab, durvalumab, trilaciclib, or any combination thereof. In some embodiments, the therapeutic agents used to treat SCLC include atezolizumab + carboplatin + etoposide, atezolizumab + carboplatin, atezolizumab + etoposide, or carboplatin + paclitaxel.

[0231] Ovarian cancer combination therapy Therapeutic agents used to treat ovarian cancer include 5-fluorouracil, albumin-bound paclitaxel, altretamine, anastrozole, bevacizumab, capecitabine, carboplatin, cisplatin, cyclophosphamide, docetaxel, doxorubicin, etoposide, exemestane, gemcitabine, ifosfamide, irinotecan, letrozole, leuprolide acetate, liposomal doxorubicin, megestrol acetate, melphalan, olaparib, oxaliplatin, paclitaxel, pazopanib, pemetrexed, tamoxifen, topotecan, vinorelbine, and any combination thereof.

[0232] Pancreatic cancer combination therapy Therapeutic agents used to treat pancreatic cancer include 5-FU, leucovorin, oxaliplatin, irinotecan, gemcitabine, nab-paclitaxel (ABRAXANE®), FOLFIRINOX, and combinations thereof. In some embodiments, therapeutic agents used to treat pancreatic cancer include 5-FU + leucovorin + oxaliplatin + irinotecan, 5-FU + nanoliposomal irinotecan, leucovorin + nanoliposomal irinotecan, and gemcitabine + nab-paclitaxel.

[0233] Prostate Cancer Combination Therapy Therapeutic agents used to treat prostate cancer include enzalutamide (XTANDI®), leuprolide, trifluridine, tipiracil (LONSURF®), cabazitaxel, prednisone, abiraterone (ZYTIGA®), docetaxel, mitoxantrone, bicalutamide, LHRH, flutamide, ADT, sabizabulin (Veru-111), and combinations thereof. In some embodiments, therapeutic agents used to treat prostate cancer include enzalutamide + leuprolide, trifluridine + tipiracil (LONSURF®), cabazitaxel + prednisone, abiraterone + prednisone, docetaxel + prednisone, mitoxantrone + prednisone, bicalutamide + LHRH, flutamide + LHRH, leuprolide + flutamide, and abiraterone + prednisone + ADT.

[0234] Additional exemplified combination therapies In some embodiments, agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are co-administered with one or more therapeutic agents selected from a PI3K inhibitor, a FLT3R agonist, a PD-1 antagonist, a PD-L1 antagonist, an MCL1 inhibitor, a CCR8 binding agent, an HPK1 antagonist, a DGKα inhibitor, a CISH inhibitor, a PARP-7 inhibitor, a Cbl-b inhibitor, a KRAS inhibitor (e.g., a KRAS G12C or G12D inhibitor), a KRAS degrader, a beta-catenin degrader, a heliose degrader, a CD73 inhibitor, an adenosine receptor antagonist, a TIGIT antagonist, a TREM1 binding agent, a TREM2 binding agent, a CD137 agonist, a GITR binding agent, an OX40 binding agent, and a CAR-T cell therapy.

[0235] In some embodiments, the agents that inhibit the binding between CD47 and SIRPα (e.g., magrolimab) and anti-Trop-2 ADCs (e.g., sacituzumab govitecan) described herein are selected from the group consisting of PI3Kδ inhibitors (e.g., idealisib), FLT3L-Fc fusion proteins (e.g., GS-3583), anti-PD-1 antibodies (pembrolizumab, nivolumab, zimberelimab), small molecule PD-L1 inhibitors (e.g., GS-4224), anti-PD-L1 antibodies (e.g., atezolizumab, avelumab), small molecule MCL1 inhibitors (e.g., GS-9716), small molecule HPK1 inhibitors (e.g., GS-6451), HPK1 degraders (PROTACs; e.g., ARV-766), small molecule DGKα inhibitors, small molecule CD73 inhibitors (e.g., quemlicustat ( AB680), anti-CD73 antibodies (e.g., oleculab), dual A2a / A2b adenosine receptor antagonists (e.g., etormadenant (AB928)), anti-TIGIT antibodies (e.g., tiragolumab, vibostolimab, domvanalimab, AB308), anti-TREM1 antibodies (e.g., PY159), anti-TREM2 antibodies (e.g., PY314), CD137 agonists (e.g., AGEN-2373), GITR / OX40 binding agents (e.g., AGEN-1223), and CAR-T cell therapy (e.g., axicabtadine ciloleucel, brexcabtadine autoleucel, tisagenlecleucel).

[0236] In some embodiments, an agent that inhibits binding between CD47 and SIRPα (e.g., magrolimab) and an anti-Trop-2 ADC (e.g., sacituzumab govitecan) described herein are co-administered with one or more therapeutic agents selected from idealisib, GS-3583, zimblerelimab, GS-4224, GS-9716, GS-6451, quemliculostat (AB680), etrumadenant (AB928), domvanalimab, AB308, PY159, PY314, AGEN-1223, AGEN-2373, axicabtadine ciloleucel, and brexcabtadine autoleucel.

[0237] 5. Medication and Scheduling The methods described herein include administration of a therapeutically effective dose of a composition, e.g., a therapeutically effective dose of an agent that inhibits binding between CD47 and SIRPα, and a therapeutically effective dose of an anti-Trop-2 ADC.

[0238] The composition is administered to the patient in an amount sufficient to substantially eliminate the target cells, as described above. An amount sufficient to achieve this is defined as a "therapeutically effective dose" that can provide an improvement in overall survival. The term "therapeutically effective amount" is an amount effective to ameliorate the symptoms of a disease (e.g., cancer as described herein). A therapeutically effective amount can be a "prophylactically effective amount" when prevention is considered a therapy. Single or multiple administrations of the composition can be administered depending on the dosage and frequency required and tolerated by the patient. The particular dose used for treatment can depend on the mammal's condition and medical history, as well as other factors such as age, weight, sex, route of administration, and efficiency.

[0239] In some embodiments, a combined therapeutic amount of an agent that inhibits binding between CD47 and SIRPα, as described herein, and an anti-Trop-2 ADC, optionally with one or more additional therapeutic agents, as described herein, can (i) reduce the number of diseased cells; (ii) reduce tumor size; (iii) inhibit, suppress, slow to some extent, and preferably stop diseased cell infiltration into peripheral organs; (iv) inhibit (e.g., slow to some extent, and preferably stop) tumor metastasis; (v) inhibit tumor growth; (vi) prevent or delay the appearance and / or recurrence of tumors; and / or (vii) alleviate to some extent one or more symptoms associated with cancer or a myeloproliferative disorder. In some embodiments, a combined therapeutic amount of an agent that inhibits binding between CD47 and SIRPα, as described herein, and an anti-Trop-2 ADC, optionally with one or more additional therapeutic agents, as described herein, can (i) reduce cancer cells; (ii) reduce tumor size; (iii) inhibit, suppress, slow to some extent, and preferably stop cancer cell invasion into peripheral organs; (iv) inhibit (e.g., slow to some extent, and preferably stop) tumor metastasis; (v) inhibit tumor growth; (vi) prevent or delay the appearance and / or recurrence of tumors, and / or (vii) relieve to some extent one or more symptoms associated with cancer. In various embodiments, the amount is sufficient to ameliorate, alleviate, reduce, and / or delay one or more symptoms of cancer.

[0240] An "increased" or "enhanced" amount (e.g., with respect to cancer cell proliferation or proliferation, anti-tumor response, cancer cell metastasis) refers to an increase that is 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, or 50 times or more (e.g., 100, 500, 1000 times) (including all integers greater than 1 and decimal points therebetween, e.g., 2.1, 2.2, 2.3, 2.4, etc.) of the amounts or levels described herein. This can also include an increase of at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150%, at least 200%, at least 500%, or at least 1000% of the amounts or levels described herein.

[0241] A "decreased" or "reduced" or "less" amount (e.g., with respect to tumor size, cancer cell proliferation or growth) refers to a decrease that is about 1.1, 1.2, 1.3, 1.4, 1.5, 1.6 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, or 50 times or more (e.g., 100, 500, 1000 times) (including all integers greater than 1 and decimal points therebetween, e.g., 1.5, 1.6, 1.7, 1.8, etc.) of the amounts or levels described herein. This can also include a decrease of at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90%, at least 100%, at least 150%, at least 200%, at least 500%, or at least 1000% of the amounts or levels described herein. In various embodiments, tumor burden is determined using a linear bidimensional method (e.g., Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (Eisenhauer, et al., Eur J Cancer. (2009) 45(2):228-47). In various embodiments, tumor burden is determined using volumetric analysis (e.g., positron emission tomography (PET) / computed tomography (CT) scan). See, e.g., Paydary, et al., Mol Imaging Biol. (2019) 21(1):1-10; Li, et al., AJR Am J Roentgenol. (2021) 217(6):1433-1443; and Kerner, et al., EJNMMI Res. (2016) Dec;6(1):33.

[0242] As used herein, "anti-tumor effect" refers to a biological effect that may be presented as a reduction in tumor volume, a reduction in the number of tumor cells, a reduction in tumor cell proliferation, a reduction in the number of metastases, an increase in overall survival or progression-free survival, an increase in life expectancy, or an improvement in various physiological symptoms associated with a tumor. Anti-tumor effect may also refer to the prevention of tumor onset or recurrence, for example, recurrence after remission.

[0243] The effective dose of the combination agent for the treatment of cancer varies depending on many different factors, including the means of administration, the target site, the physiological condition of the patient, whether the patient is human or animal, other medications administered, and whether the treatment is prophylactic or therapeutic. Usually, the patient is a human, but non-human mammals, such as companion animals such as dogs, cats, horses, non-human primates, and experimental animals such as rabbits, mice, and rats, can also be treated. The therapeutic dose can be set to optimize safety and efficacy.

[0244] A therapeutically effective dose of an anti-CD47 antibody can depend on the particular agent used, but is typically about 10 mg / kg body weight or more (e.g., about 10 mg / kg or more, about 15 mg / kg or more, about 20 mg / kg or more, about 25 mg / kg or more, about 30 mg / kg or more, about 35 mg / kg or more, about 40 mg / kg or more, about 45 mg / kg or more, about 50 mg / kg or more, or about 55 mg or more, or about 60 mg / kg or more, or about 65 mg or more, or about 70 mg / kg or more), or from about 10 mg / kg, from about 15 mg / kg to about 70 mg / kg (e.g., from about 10 mg / kg to about 67.5 mg / kg, or from about 10 mg / kg, from about 15 mg / kg to about 60 mg / kg).

[0245] In some embodiments, the therapeutically effective dose of the anti-CD47 antibody is 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, or 67.5 mg / kg. In some embodiments, the therapeutically effective dose of the anti-CD47 antibody is 10-60 mg / kg. In some embodiments, the therapeutically effective dose of the anti-CD47 antibody is 10-67.5 mg / kg. In some embodiments, the anti-CD47 antibody is administered at a dose of at least 10-30, 20-30, 15-60, 30-60, 10, 15, 20, 30, 40, 45, 50, or 60 mg of antibody per kg of body weight.

[0246] The therapeutic dose of the anti-CD47 antibody can be a fixed dose. For example, a fixed dose can be administered regardless of the weight of a particular subject. Alternatively, the fixed dose can be given based on the weight of a particular subject within a particular weight range, for example, a first range of 100 kg or less, or a second range of more than 100 kg. The fixed dose can be, for example, 1000-5000, 2000-4000, 2000-3500, 2400-3500, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2100, 2200, 2300, 2400, 2500, 2600, 2700, 2800, 2900, 3000, 3100, 3200, 3300, 3400, 3500, 3600, 3700, 3800, 3900, 4000, 4100, 4200, 4300, 4400, 4500, 4600, 4700, 4800, 4900, 5000, 5100, 5200, 5300, 5400, 5500, 5600, 5700, 5800, 5900, 6000, 6100, 6200, 6300, 6400, 6500, 6600, 6700, 6800, 6900, 7000, 7100, 00, 2800, 2900, 3000, 3100, 3200, 3300, 3400, 3500, 3600, 3700, 3800, 3900, 4000, 4100, 4200, 4300, 4400, 4500, 4600, 4700, 4800, 4900, 5000 mg, or any intermediate number thereof.

[0247] The method may include administering a primer agent to the subject, followed by administering a therapeutically effective dose of anti-CD47 to the subject. In some embodiments, administering the therapeutically effective dose occurs at least about 3 days (e.g., at least about 4 days, at least about 5 days, at least about 6 days, at least about 7 days, at least about 8 days, at least about 9 days, or at least about 10 days) after initiating administration of the primer agent. This period of time is sufficient, for example, to provide enhanced reticulocyte production by the individual. In some embodiments, the anti-CD47 agent is an isolated anti-CD47 antibody.

[0248] Administration of a therapeutically effective dose of anti-CD47 can be achieved in many different ways. In some cases, after the primer agent is administered, two or more therapeutically effective doses are administered. Suitable administration of a therapeutically effective dose can involve administration of a single dose, or can involve administration of doses daily, twice weekly, weekly, biweekly, monthly, annually, etc. In some cases, a therapeutically effective dose is administered as two or more doses of increasing concentration (i.e., increasing doses), where (i) all of the doses are therapeutic doses, or (ii) a sub-therapeutic dose (or two or more sub-therapeutic doses) are given initially, and a therapeutic dose is achieved by the escalation. As one non-limiting example to illustrate escalating concentrations (i.e., increasing doses), a therapeutically effective dose can be administered weekly, beginning with a sub-therapeutic dose (e.g., a dose less than 10 mg / kg, e.g., 5 mg / kg, 4 mg / kg, 3 mg / kg, 2 mg / kg, or 1 mg / kg), and each subsequent dose can be increased by a particular increment (e.g., 5 mg / kg, 10 mg / kg, 15 mg / kg) or by various increments until a therapeutic dose (e.g., 15 mg / kg, 30 mg / kg, 45 mg / kg, 60 mg / kg) is reached, at which point administration can be stopped or continued with one or more additional therapeutic doses (e.g., a continued therapeutic dose, or an escalating therapeutic dose, e.g., a dose of 15 mg / kg, 30 mg / kg, 45 mg / kg, 60 mg / kg). As another non-limiting example to illustrate escalating concentrations (i.e., increasing doses), a therapeutically effective dose can be administered weekly, beginning with one or more relatively low therapeutic doses (e.g., doses of 10 mg / kg, 15 mg / kg, or 30 mg / kg), with each subsequent dose increasing by a particular increment (e.g., 10 mg / kg or 15 mg / kg) or by various increments until a relatively high therapeutic dose (e.g., 30 mg / kg, 45 mg / kg, 60 mg / kg, 100 mg / kg, etc.) is reached, at which point administration can be stopped or continued (e.g., one or more continued or escalating therapeutic doses, e.g., doses of 30 mg / kg, 45 mg / kg, 60 mg / kg, 100 mg / kg).In various embodiments, a relatively low therapeutic dose is administered more frequently (e.g., two or more doses of 15 mg / kg administered weekly (Q1W) or two or more doses of 30 mg / kg administered every two weeks (Q2W)) and a relatively high therapeutic dose is administered less frequently (e.g., two or more doses of 45 mg / kg administered every three weeks (Q3W) or two or more doses of 60 mg / kg administered monthly or every four weeks (Q4W)). In some embodiments, administration of the therapeutically effective dose may be a continuous infusion, and the dose may be varied (e.g., escalated) over time.

[0249] The dose required to achieve and / or maintain a particular serum level of the administered composition is proportional to the time between doses and inversely proportional to the dose administered. Thus, as the frequency of administration increases, the required dose decreases. Optimization of the administration strategy will be readily understood and performed by those skilled in the art. Exemplary treatment regimens involve administration once every two weeks, or once a month, or once every three to six months. The therapeutics described herein are typically administered multiple times. The interval between single doses can be weeks, months, or years. The interval can also be irregular as indicated by measuring the blood levels of the therapeutic in the patient. Alternatively, the therapeutics described herein can be administered as sustained release formulations, in which case less frequent administration is used. The dosage and frequency will vary depending on the half-life of the polypeptide in the patient. In some embodiments, the interval between each single dose is one week. In some embodiments, the interval between each single dose is two weeks. In some embodiments, the interval between each single dose is three weeks. In some embodiments, the interval between each single dose is four weeks. In some embodiments, the interval between each single dose of anti-CD47 antibody is 1 week. In some embodiments, the interval between each single dose of anti-CD47 antibody is 2 weeks. In some embodiments, the interval between each single dose of anti-CD47 antibody is 3 weeks. In some embodiments, the interval between each single dose of anti-CD47 antibody is 4 weeks. In some embodiments, the interval between each single dose of magrolimab is 1 week. In some embodiments, the interval between each single dose of magrolimab is 2 weeks. In some embodiments, the interval between each single dose of magrolimab is 3 weeks. In some embodiments, the interval between each single dose of magrolimab is 4 weeks.

[0250] "Maintenance dose" is a dose intended to be a therapeutically effective dose.For example, in an experiment to determine a therapeutically effective dose, multiple different maintenance doses can be administered to different subjects.Therefore, some of the maintenance doses can be therapeutically effective doses, and others can be sub-therapeutic doses.

[0251] In prophylactic applications, relatively low dosages may be administered at relatively infrequent intervals over an extended period of time. Some patients continue to receive treatment for the rest of their lives. In other therapeutic applications, relatively high dosages at relatively short intervals may be used until the progression of the disease is reduced or terminated, preferably until the patient shows partial or complete improvement in the symptoms of the disease. The patient can then be administered a prophylactic regimen.

[0252] The term "sub-therapeutic dose" is a dose that is insufficient to effect a desired clinical outcome. For example, a sub-therapeutic dose of a CD47 or SIRPα binding agent or an anti-Trop-2 ADC is an amount that is insufficient to palliate, ameliorate, stabilize, reverse, prevent, slow or delay the progression of a disease state (e.g., a cancer, such as a Trop-2-expressing cancer, as described herein).

[0253] The term "priming dose" or "priming dose" as used herein refers to a dose of an anti-CD47 antibody that primes a subject to receive a therapeutically effective dose of the anti-CD47 antibody such that the therapeutically effective dose does not result in severe loss of RBCs (reduction in hematocrit or reduction in hemoglobin). The particular appropriate priming dose of an anti-CD47 antibody may vary depending on the nature of the agent used and a number of subject-specific factors (e.g., age, weight, etc.). Examples of suitable priming doses of an anti-CD47 antibody include about 0.5 mg / kg to about 5 mg / kg, about 0.5 mg / kg to about 4 mg / kg, about 0.5 mg / kg to about 3 mg / kg, about 1 mg / kg to about 5 mg / kg, about 1 mg / kg to about 4 mg / kg, about 1 mg / kg to about 3 mg / kg, about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, and about 5 mg / kg. In some embodiments, the priming dose is preferably 1 mg / kg.

[0254] In some embodiments of the methods described herein, the anti-CD47 antibody is administered to the subject as a priming dose in the range of about 0.5 mg to about 10 mg, e.g., about 0.5 to about 5 mg / kg antibody, optionally 4 mg / kg, 3 mg / kg, 2 mg / kg, or 1 mg / kg antibody. In some embodiments, the anti-CD47 antibody is administered to the subject as a therapeutic dose in the range of about 20 to about 67.5 mg / kg antibody, optionally 15 to 60 mg / kg antibody, optionally 30 to 60 mg / kg antibody, optionally 15 mg / kg antibody, 20 mg / kg antibody, 30 mg / kg antibody, 45 mg / kg antibody, 60 mg / kg antibody, or 67.5 mg / kg antibody.

[0255] The priming dose of the anti-CD47 antibody can be a constant priming dose. For example, the constant priming dose can be administered regardless of the weight of the particular subject. Alternatively, the constant priming dose can be given based on the weight of the particular subject within a particular weight range, for example, a first range of 100 kg or less, or a second range of 100 kg or more. The constant priming dose can be, for example, 10-200, 50-100, 80-800, 80-400, 80-200, 70-90, 75-85, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 240, 300, 320, 400, 500, 600, 700, or 800 mg, or any intermediate number of mg therebetween.

[0256] In some embodiments, an effective priming dose of magrolimab is provided, where an effective priming dose in a human is approximately about 1 mg / kg, e.g., at least about 0.5 mg / kg to a maximum of about 5 mg / kg or less, at least about 0.75 mg / kg to a maximum of about 1.25 mg / kg or less, at least about 0.95 mg / kg to a maximum of about 1.05 mg / kg or less, and can be approximately 1 mg / kg.

[0257] In some embodiments, the initial dose of CD47 or SIRPα binding agent is infused over a period of at least about 2 hours, at least about 2.5 hours, at least about 3 hours, at least about 3.5 hours, at least about 4 hours, at least about 4.5 hours, at least about 5 hours, at least about 6 hours, or more. In some embodiments, the initial dose is infused over a period of about 2.5 hours to about 6 hours, e.g., about 3 hours to about 4 hours. In some such embodiments, the dose of agent in the infusion is about 0.05 mg / ml to about 0.5 mg / ml, e.g., about 0.1 mg / ml to about 0.25 mg / ml.

[0258] In other embodiments, the first dose, e.g., a priming dose, of the CD47 or SIRPα binding agent is administered by continuous infusion, e.g., an osmotic pump, delivery patch, etc., where the dose is administered over a period of at least about 6 hours, at least about 12 hours, at least about 24 hours, at least about 2 days, at least about 3 days. Many such systems are known in the art. For example, the DUROS technology provides a two-compartment system separated by a piston. One of the compartments consists of an osmotic engine specifically formulated with excess solid NaCl, which is present throughout the entire delivery period, resulting in a constant osmotic gradient. It also consists of a semipermeable membrane at one end through which water is drawn into the osmotic engine, establishing a large and constant osmotic gradient between the tissue fluid and the osmotic engine. The other compartment consists of a drug solution and has an opening through which the drug is released by the osmotic gradient. This helps provide site-specific and systemic drug delivery when implanted in a human. The preferred site of implantation is subcutaneous placement on the inside of the upper arm.

[0259] Following administration of the priming agent, a therapeutic dose of an anti-CD47 or anti-SIRPα agent is administered, allowing for a period of time effective for increased reticulocyte production. The therapeutic dose can be administered in many different ways. In some embodiments, the priming agent is administered, followed by two or more therapeutically effective doses, for example, on a weekly dosing schedule. In some embodiments, the therapeutically effective dose of the anti-CD47 agent is administered as two or more doses of increasing concentration, while in other embodiments, the doses are the same. Red hemagglutination is reduced after the priming dose.

[0260] The therapeutically effective dose of an anti-SIRPα antibody can depend on the particular agent used, but is typically about 10 mg or more, e.g., about 30 mg, 50 mg, 100 mg, 200 mg, 400 mg, or 800 mg or more. For example, multiple administrations of an anti-SIRPα antibody that does not have Fc effector function can be administered at regular intervals, e.g., every 2 weeks (Q2W), every 3 weeks (Q3W), every 4 weeks (Q4W), over an extended period of time, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 months.

[0261] With respect to administration of an anti-Trop-2 ADC (e.g., sacituzumab govitecan), in some embodiments, sacituzumab govitecan is administered at one or more doses ranging from 3 mg / kg to 18 mg / kg, e.g., 8 mg / kg to 10 mg / kg. In some embodiments, the anti-Trop-2 ADC (e.g., sacituzumab govitecan) is administered at one or more doses of 10 mg / kg.

[0262] In some embodiments, magrolimab is administered initially at a priming dose of 1 mg / kg, then at one or more therapeutic doses of 30 mg / kg, followed by one or more therapeutic doses of 60 mg / kg. In some embodiments, magrolimab is administered initially at a priming dose of 1 mg / kg, then at one or more therapeutic doses of 20 mg / kg, followed by one or more therapeutic doses of 45 mg / kg. In some embodiments, magrolimab is administered initially at a priming dose of 1 mg / kg, then at one or more therapeutic doses of 15 mg / kg, followed by one or more therapeutic doses of 30 mg / kg.

[0263] In some embodiments, magrolimab and sacituzumab govitecan are administered in a first 21 day cycle, a second 21 day cycle, and a third 21 day cycle, wherein: (a) in a first 21-day cycle, magrolimab is administered at a dose of 1 mg / kg on day 1 and at a dose of 30 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1, or 2, and 8 (i.e., on days 1 and 8, or on days 2 and 8); b) in a second 21-day cycle, magrolimab is administered at a dose of 30 mg / kg on days 1, 8, and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8; and c) In a third 21-day cycle, magrolimab is administered at a dose of 60 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8.

[0264] In some embodiments, magrolimab and sacituzumab govitecan are administered in a first 21 day cycle, a second 21 day cycle, and a third 21 day cycle, wherein: (a) in a first 21-day cycle, magrolimab is administered at a dose of 1 mg / kg on day 1 and at a dose of 20 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1, or 2, and 8 (i.e., on days 1 and 8, or on days 2 and 8); b) in a second 21-day cycle, magrolimab is administered at a dose of 20 mg / kg on days 1, 8, and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8; and c) In a third 21-day cycle, magrolimab is administered at a dose of 45 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8.

[0265] In some embodiments, magrolimab and sacituzumab govitecan are administered in a first 21 day cycle, a second 21 day cycle, and a third 21 day cycle, wherein: (a) in a first 21-day cycle, magrolimab is administered at a dose of 1 mg / kg on day 1 and at a dose of 15 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1, or 2, and 8 (i.e., on days 1 and 8, or on days 2 and 8); b) in a second 21-day cycle, magrolimab is administered at a dose of 15 mg / kg on days 1, 8, and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8; and c) In a third 21-day cycle, magrolimab is administered at a dose of 30 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8.

[0266] In some embodiments, the agent that inhibits binding between CD47 and SIRPα and the anti-Trop-2 ADC are administered in a combined synergistic amount. As used herein, a "combined synergistic amount" refers to the sum of a first amount (e.g., the amount of an agent that inhibits binding between CD47 and SIRPα) and a second amount (e.g., the amount of an anti-Trop-2 ADC) that results in a synergistic effect (i.e., an effect that is greater than additive). Thus, the terms "synergy," "synergistic," "synergistic," "combined synergistic amount," and "synergistic therapeutic effect," as used interchangeably herein, refer to a measured effect of compounds administered in combination that is greater than the sum of the individual effects of each compound administered alone as a single agent.

[0267] Co-administration of an agent that inhibits binding between CD47 and SIRPα with an anti-Trop-2 ADC allows for lower doses of one or both therapeutic agents. In embodiments, a synergistic amount can be about 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% of the amount of the agent that inhibits binding between CD47 and SIRPα when used separately from the anti-Trop-2 ADC. In embodiments, a synergistic amount may be about 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% of the amount of an anti-Trop-2 ADC when used separately from the agent that inhibits binding between CD47 and SIRPα.

[0268] Dosage and frequency may vary depending on the half-life of the therapeutic agent in the patient. Those skilled in the art will appreciate that such guidelines are adjusted for the molecular weight of the active agent, for example, in the use of antibody fragments, in the use of antibody conjugates, in the use of SIRPα reagents, in the use of soluble CD47 peptides, and the like. Dosage may also vary appropriately for local administration, e.g., intranasally, inhalation, etc., or systemic administration, e.g., intramuscular (im), intraperitoneal (ip), intravenous (iv), subcutaneous (sc), intratumoral, intracranial. In some embodiments, magrolimab is administered intravenously, e.g., through an in-line filter, e.g., through an in-line filter having a pore size of 5 μm, e.g., through an in-line filter having a pore size of 1.2 μm, e.g., through an in-line filter having a pore size of 0.45 μm, e.g., through an in-line filter having a pore size of 0.22 μm. In some embodiments, the agent that inhibits binding between CD47 and SIRPα and the anti-Trop-2 ADC are administered simultaneously. In some embodiments, the agent that inhibits binding between CD47 and SIRPα and the anti-Trop-2 ADC are administered sequentially. For example, the agent that inhibits binding between CD47 and SIRPα described herein may be administered within seconds, minutes, hours, or days of administration of the anti-Trop-2 ADC. In some embodiments, a unit dose of the agent that inhibits binding between CD47 and SIRPα is administered first, followed within seconds, minutes, hours, or days by a unit dose of the anti-Trop-2 ADC. Alternatively, a unit dose of the anti-Trop-2 ADC is administered first, followed within seconds, minutes, hours, or days by a unit dose of the agent that inhibits binding between CD47 and SIRPα. In other embodiments, a unit dose of an agent that inhibits binding between CD47 and SIRPα is administered first, followed several hours (e.g., 1-12 hours, 1-24 hours, 1-36 hours, 1-48 hours, 1-60 hours, 1-72 hours) later by administration of a unit dose of an anti-Trop-2 ADC.In yet other embodiments, a unit dose of an anti-Trop-2 ADC is administered first, followed several hours (e.g., 1-12 hours, 1-24 hours, 1-36 hours, 1-48 hours, 1-60 hours, 1-72 hours) later by administration of a unit dose of an agent that inhibits binding between CD47 and SIRPα.

[0269] 6. Condition receiving treatment Methods are provided for treating, ameliorating, alleviating, or preventing or delaying the growth, proliferation, recurrence, or metastasis of cancer in a subject, the methods comprising administering to the subject (a) an agent that inhibits binding between CD47 and SIRPα, and (b) an anti-Trop-2 ADC. In some embodiments, the subject is a human.

[0270] As used herein, "treatment" or "treating" is an approach to obtain beneficial or desired results, including clinical results. For example, beneficial or desired clinical results may include one or more of the following: (i) reducing another symptom caused by the disease, (ii) reducing the extent of the disease and stabilizing the disease (e.g., preventing or delaying the worsening of the disease), (iii) preventing or delaying the spread of the disease (e.g., metastasis), (iv) preventing or delaying the onset or recurrence of the disease, delaying or slowing the progression of the disease, (v) improving the disease state, providing remission (partial or total) of the disease, reducing the dose of one or more other medications required to treat the disease, (vi) delaying the progression of the disease and improving the quality of life, and / or (vii) prolonging survival. Beneficial or desired clinical results may be observed in more patients or subjects who have undergone the methods or treatments described herein. In some embodiments, the cancer has progres...

Claims

1. A method of treating, alleviating, reducing, preventing or delaying the growth, proliferation, recurrence or metastasis of a Trop-2 positive cancer in a mammalian subject in need thereof, comprising administering to the subject an effective amount of a) an anti-Trop-2 antibody-drug conjugate (ADC); and b) Agents that inhibit the binding of CD47 to SIRPα and

2. The method of claim 1 , wherein the cancer is a solid epithelial cancer.

3. 3. The method of claim 1 or 2, wherein the cancer is selected from breast cancer (e.g., triple-negative breast cancer), colorectal cancer, lung cancer, gastric cancer, urinary tract cancer, urothelial cancer, bladder cancer, kidney cancer, pancreatic cancer, ovarian cancer, uterine cancer, esophageal cancer and prostate cancer.

4. The method of any one of claims 1 to 3, wherein the cancer is (i) unresectable, locally advanced, or (ii) metastatic.

5. The method of any one of claims 1 to 4, wherein the cancer is unresectable, locally advanced, and the subject is treatment naive.

6. The method of any one of claims 1 to 5, wherein the cancer is selected from metastatic breast cancer, metastatic non-small cell lung cancer, metastatic small cell lung cancer, metastatic urothelial cancer, and metastatic pancreatic cancer.

7. The method of any one of claims 1 to 6, wherein the cancer is a breast cancer selected from triple negative breast cancer, HR+ / HER2- breast cancer, and HER2+ breast cancer.

8. The method of any one of claims 1 to 6, wherein the cancer is a lung cancer selected from non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).

9. 9. The method of any one of claims 1-8, wherein the treatment results in a reduction in total tumor burden of at least 15%, at least 20%, at least 30%, or at least 40% as determined using a linear bidimensional method (e.g., RECIST v1.1).

10. The method of any one of claims 1 to 9, comprising reducing the size of said metastases or eliminating said metastases.

11. 11. The method of any one of claims 1 to 10, wherein the cancer does not recur or the tumor mass does not regrow after cessation of treatment.

12. The method of any one of claims 1 to 11, wherein the cancer has cell surface expression of CD47.

13. The method of any one of claims 1 to 12, wherein the agent that inhibits binding between CD47 and SIRPα comprises an antibody that binds to CD47.

14. 14. The method of claim 13, wherein the antibody that binds to CD47 is selected from magrolimab, lemzoparlimab, retaplimab, ligufalimab, AO-176, simlidarlimab (IBI-322), gentulizumab, ZL-1201, IMC-002, SRF-231, CC-90002 (also known as INBRX-103), NI-1701 (also known as TG-1801), and STI-6643.

15. The method of any one of claims 1 to 12, wherein the agent that inhibits binding between CD47 and SIRPα comprises an antibody that binds to SIRPα.

16. The method of claim 13, wherein the antibody that binds to SIRPα is selected from GS-0189 (also known as FSI-189), CC-95251, BI-765063, and APX-700.

17. The method of any one of claims 1 to 12, wherein the agent that inhibits binding between CD47 and SIRPα comprises a SIRPα-Fc fusion protein.

18. 18. The method of claim 17, wherein the SIRPα-Fc fusion protein is selected from ALX-148 (evoluptor), timdarpacept, TTI-621, TTI-622, JMT601 (CPO107), and SL-172154.

19. 19. The method of any one of claims 1 to 18, wherein the anti-Trop-2 ADC comprises a topoisomerase I inhibitor.

20. 20. The method of claim 19, wherein the topoisomerase I inhibitor is selected from irinotecan, topetecan, and SN-38.

21. The method of any one of claims 1 to 20, wherein the anti-Trop-2 ADC has the structural formula of mAb-CL2A-SN-38, the structure being represented by: 【Chemistry 4】 (For example, as described in US Pat. No. 7,999,083).

22. 22. The method of any one of claims 1 to 21, wherein the anti-Trop-2 ADC comprises sacituzumab (hRS7; e.g., as described in WO2003074566, Figures 3 and 4).

23. 23. The method of any one of claims 1 to 22, wherein the anti-Trop-2 ADC is selected from sacituzumab govitecan, datopotamab deruxtecan (DS-1062), ESG-401, SKB-264, DAC-02, and BAT-8003.

24. 24. The method of any one of claims 1-23, wherein the anti-Trop-2 ADC comprises sacituzumab govitecan.

25. 25. The method of any one of claims 1 to 24, wherein the agent that inhibits binding between CD47 and SIRPα and the anti-Trop-2 ADC are administered simultaneously.

26. 25. The method of any one of claims 1 to 24, wherein the agent that inhibits binding between CD47 and SIRPα and the anti-Trop-2 ADC are administered sequentially.

27. The method of any one of claims 1 to 26, wherein the agent that inhibits binding between CD47 and SIRPα is administered at a sub-therapeutic dose.

28. 28. The method of any one of claims 1 to 27, wherein the anti-Trop-2 ADC is administered at a sub-therapeutic dose.

29. 29. The method of any one of claims 1 to 28, wherein the agent that inhibits binding between CD47 and SIRPα and the anti-Trop-2 ADC are co-administered at sub-therapeutic doses.

30. 30. The method of any one of claims 1 to 29, further comprising administering a taxane.

31. 31. The method of claim 30, wherein the taxane is selected from paclitaxel, nab-paclitaxel (ABRAXANE®), docetaxel, and cabazitaxel.

32. The method of any one of claims 1 to 31, further comprising administering one or more therapeutic antibodies.

33. 33. The method of any one of claims 1 to 32, further comprising co-administering one or more blockers or inhibitors of one or more T cell stimulatory immune checkpoint proteins or receptors.

34. 34. The method of claim 33, wherein the one or more immune checkpoint inhibitors comprise a proteinaceous (e.g., antibody) inhibitor of PD-L1 (CD274), PD-1 (PDCD1), or CTLA4.

35. 35. The method of any one of claims 33-34, wherein the one or more immune checkpoint proteins or receptors are selected from CD274 (CD274, PDL1, PD-L1) and Programmed Cell Death 1 (PDCD1, PD1, PD-1).

36. The proteinaceous (e.g., antibody) inhibitor of CTLA4 is selected from the group consisting of ipilimumab, tremelimumab, BMS-986218, AGEN1181, AGEN1884 (zalifrelimab), BMS-986249, MK-1308, REGN-4659, ADU-1604, CS-1002, BCD-145, APL-509, JS-007, BA-3071, ONC-392, AGEN-2041, JHL-1155, KN-044, CG-01 61, ATOR-1144, PBI-5D3H5, FPT-155 (CTLA4 / PD-L1 / CD28), PF-06936308 (PD-1 / CTLA4), MGD-019 (PD-1 / CTLA4), KN-046 (PD-1 / CTLA4), MEDI-5752 (CTLA4 / PD-1), XmAb-20717 (PD-1 / CTLA4), and AK-104 (CTLA4 / PD-1).

37. The proteinaceous (e.g., antibody) inhibitor of programmed cell death 1 (PDCD1; NCBI Gene ID: 5133; CD279, PD-1, PD1) is selected from the group consisting of zimberelimab (AB122, GLS-010, WBP-3055), pembrolizumab (KEYTRUDA®, MK-3475, SCH900475), nivolumab (OPDIVO®, BMS-936558, MDX-1106), cemiplimab (LIBTAYO®; cemiplimab-rwlc, REGN-2810), pidilizumab (CT-011), AMG-404, MEDI0680 (AMP-514), spartalisumab (CT-01 ... (PDR001), tislelizumab (BGB-A317), toripalimab (JS-001), genolimuzumab (CBT-501, APL-501, GB226), SHR-1201, camrelizumab (SHR-1210), sintilimab (TYVYT®; IBI-308), dostallimab (TSR-042, WBP-285), lambrolizumab (MK-3475); sasanlimumab (PF-06801591), cetrelimab (JNJ-63723283), serplulimab (HLX-10), retifanlimab (MGA-012), balstilimab (AGEN2034), prorugolimab (BCD 100), budigalimab (ABBV-181), bopratelimab (JTX-4014), AK-103 (HX-008), AK-105, CS-1003, BI-754091, LZM-009, Sym-021, BAT-1306, PD1-PIK, tebotelimab (MGD013; PD-1 / LAG-3), RO-7247669 (PD-1 / LAG-3), FS-118 (LAG-3 / PD-L1), RO-712166 36. The method of any one of claims 33 to 35, wherein the antibody is selected from the group consisting of PD-1 / TIM-3, RG7769 (PD-1 / TIM-3), PF-06936308 (PD-1 / CTLA4), MGD-019 (PD-1 / CTLA4), KN-046 (PD-1 / CTLA4), XmAb-20717 (PD-1 / CTLA4), AK-104 (CTLA4 / PD-1), and MEDI-5752 (CTLA4 / PD-1).

38. The proteinaceous (e.g., antibody) inhibitor of the CD274 molecule (NCBI Gene ID: Gene ID:29126; B7-H, B7H1, PD-L1) is selected from the group consisting of atezolizumab (TECENTRIQ®), avelumab (BAVENCIO®; MSB0010718C), embafolimab (ASC22), durvalumab (IMFINZI®; MEDI-4736), BMS-936559 (MDX1105), cosibelimab (CK-301), lodapolimab (LY3300054), galibrimab (BGB A333), embafolimab (KN035), opucolimab (HLX20), manelimab (BCD135), CX-072, CBT-502 (TQB2450), MSB-2311, SHR-1316, sugemalimab (CS-1001; WBP3155), A167 (KL-A167, HBM9167), STI-A1015 (IMC-001), FAZ-053, BMS-936559 (MDX1105), INCB086550, GEN-104 6 (PD-L1 / 4-1BB), FPT-155 (CTLA4 / PD-L1 / CD28), M7824 (PD-L1 / TGFβ-EC domain), CA-170 (PD-L1 / VISTA), CDX-527 (CD27 / PD-L1), LY-3415244 (TIM-3 / PDL1), INBRX-105 (4-1BB / PDL1), and GNS-1480 (PD-L1 / EGFR).

39. 39. The method of any one of claims 1 to 38, further comprising co-administering an agonist of fms-related receptor tyrosine kinase 3 (FLT3).

40. 40. The method of claim 39, wherein said agonist of FLT3 is selected from GS-3583 and CDX-301.

41. 41. The method of any one of claims 1 to 40, wherein the agent that inhibits binding between CD47 and SIRPα and the anti-Trop-2 ADC are administered in a combined synergistic amount.

42. 42. The method of any one of claims 1 to 41, wherein administration of the agent that inhibits binding between CD47 and SIRPα and the anti-Trop-2 ADC results in a synergistic effect.

43. 43. The method of claim 42, wherein the synergistic effect is an increase in cancer cell death and / or a decrease in cancer cell growth when comparing the effect of the combination to either the agent that inhibits binding between CD47 and SIRPα or the anti-Trop-2 ADC alone.

44. 43. The method of claim 42, wherein the synergistic effect is an increase in phagocytosis of cancer cells by macrophages when comparing the effect of the combination to either the agent that inhibits binding between CD47 and SIRPα or the anti-Trop-2 ADC alone.

45. 43. The method of claim 42, wherein the synergistic effect is an increase or enhancement in tumor burden reduction when comparing the effect of the combination to either the agent that inhibits binding between CD47 and SIRPα or the anti-Trop-2 ADC alone.

46. The method of any one of claims 1 to 45, wherein the subject is a human.

47. 47. The method of any one of claims 1 to 46, wherein the cancer has progressed after at least one previous anti-cancer therapy.

48. The method of any one of claims 1 to 46, wherein the subject is treatment naive.

49. 1. A method of treating, alleviating, reducing, preventing or delaying the growth, proliferation, recurrence or metastasis of cancer in a subject, comprising administering to the subject effective amounts of: (a) magrolimab; and (b) sacituzumab govitecan.

50. 50. The method of claim 49, wherein the cancer is a solid epithelial cancer.

51. 51. The method of any one of claims 49 to 50, wherein the cancer is selected from breast cancer (e.g. triple negative breast cancer), colorectal cancer, lung cancer, gastric cancer, urinary tract cancer, urothelial cancer, bladder cancer, renal cancer, pancreatic cancer, ovarian cancer, uterine cancer, esophageal cancer and prostate cancer.

52. 52. The method of any one of claims 49 to 51, wherein the cancer is (i) unresectable, locally advanced, or (ii) metastatic.

53. 53. The method of any one of claims 49-52, wherein the cancer is unresectable, locally advanced, and the subject is treatment naive.

54. 54. The method of any one of claims 49 to 53, wherein the cancer is selected from metastatic non-small cell lung cancer, metastatic small cell lung cancer, metastatic urothelial cancer, and metastatic pancreatic cancer.

55. 55. The method of any one of claims 49 to 54, wherein the cancer is a breast cancer selected from triple negative breast cancer, HR+ / HER2- breast cancer, and HER2+ breast cancer.

56. 55. The method of any one of claims 49 to 54, wherein the cancer is a lung cancer selected from non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).

57. 57. The method of any one of claims 49-56, wherein the treatment results in a reduction in total tumor burden of at least 15%, at least 20%, at least 30%, or at least 40% as determined using a linear bidimensional method (e.g., RECIST v1.1).

58. 58. A method according to any one of claims 49 to 57, comprising reducing the size of said metastases or eliminating said metastases.

59. 59. The method of any one of claims 49-58, wherein the cancer does not recur or the tumor mass does not regrow after cessation of treatment.

60. 60. The method of any one of claims 49 to 59, wherein the cancer has cell surface expression of CD47.

61. 61. The method of any one of claims 49-60, wherein the magrolimab and the sacituzumab govitecan are administered simultaneously.

62. 61. The method of any one of claims 49-60, wherein the magrolimab and the sacituzumab govitecan are administered sequentially.

63. 63. The method of any one of claims 49-62, wherein the magrolimab is administered at a sub-therapeutic dose.

64. 64. The method of any one of claims 49-63, wherein the sacituzumab govitecan is administered at a subtherapeutic dose.

65. 65. The method of any one of claims 49-64, wherein the magrolimab and the sacituzumab govitecan are co-administered at sub-therapeutic doses.

66. 66. The method of any one of claims 49 to 65, further comprising administering a taxane.

67. 67. The method of claim 66, wherein the taxane is selected from paclitaxel, nab-paclitaxel (ABRAXANE®), docetaxel, and cabazitaxel.

68. 68. The method of any one of claims 49 to 67, further comprising co-administering one or more therapeutic antibodies.

69. 69. The method of any one of claims 49-68, further comprising co-administering one or more blockers or inhibitors of one or more T cell stimulatory immune checkpoint proteins or receptors.

70. 70. The method of claim 69, wherein the one or more immune checkpoint inhibitors comprise a proteinaceous (e.g., antibody) inhibitor of PD-L1 (CD274), PD-1 (PDCD1), or CTLA4.

71. 71. The method of any one of claims 68 to 70, wherein the one or more immune checkpoint proteins or receptors are selected from CD274 (CD274, PDL1, PD-L1) and Programmed Cell Death 1 (PDCD1, PD1, PD-1).

72. The proteinaceous (e.g., antibody) inhibitor of CTLA4 is selected from the group consisting of ipilimumab, tremelimumab, BMS-986218, AGEN1181, AGEN1884 (zalifrelimab), BMS-986249, MK-1308, REGN-4659, ADU-1604, CS-1002, BCD-145, APL-509, JS-007, BA-3071, ONC-392, AGEN-2041, JHL-1155, KN-044, CG-01 61, ATOR-1144, PBI-5D3H5, FPT-155 (CTLA4 / PD-L1 / CD28), PF-06936308 (PD-1 / CTLA4), MGD-019 (PD-1 / CTLA4), KN-046 (PD-1 / CTLA4), MEDI-5752 (CTLA4 / PD-1), XmAb-20717 (PD-1 / CTLA4), and AK-104 (CTLA4 / PD-1).

73. The proteinaceous (e.g., antibody) inhibitor of programmed cell death 1 (PDCD1; NCBI Gene ID: 5133; CD279, PD-1, PD1) is selected from the group consisting of zimberelimab (AB122, GLS-010, WBP-3055), pembrolizumab (KEYTRUDA®, MK-3475, SCH900475), nivolumab (OPDIVO®, BMS-936558, MDX-1106), cemiplimab (LIBTAYO®; cemiplimab-rwlc, REGN-2810), pidilizumab (CT-011), AMG-404, MEDI0680 (AMP-514), spartalisumab (CT-01 ... (PDR001), tislelizumab (BGB-A317), toripalimab (JS-001), genolimuzumab (CBT-501, APL-501, GB226), SHR-1201, camrelizumab (SHR-1210), sintilimab (TYVYT®, IBI-308), dostallimab (TSR-042, WBP-285), lambrolizumab (MK-3475); sasanlimumab (PF-06801591), cetrelimab (JNJ-63723283), serplulimab (HLX-10), retifanlimab (MGA-012), balstilimab (AGEN2034), prorugolimab (BCD 100), budigalimab (ABBV-181), bopratelimab (JTX-4014), AK-103 (HX-008), AK-105, CS-1003, BI-754091, LZM-009, Sym-021, BAT-1306, PD1-PIK, tebotelimab (MGD013; PD-1 / LAG-3), RO-7247669 (PD-1 / LAG-3), FS-118 (LAG-3 / PD-L1), RO-712166 72. The method of any one of claims 69 to 71, wherein the antibody is selected from the group consisting of PD-1 / TIM-3, RG7769 (PD-1 / TIM-3), PF-06936308 (PD-1 / CTLA4), MGD-019 (PD-1 / CTLA4), KN-046 (PD-1 / CTLA4), XmAb-20717 (PD-1 / CTLA4), AK-104 (CTLA4 / PD-1), and MEDI-5752 (CTLA4 / PD-1).

74. The proteinaceous (e.g., antibody) inhibitor of the CD274 molecule (NCBI Gene ID: Gene ID:29126; B7-H, B7H1, PD-L1) is selected from the group consisting of atezolizumab (TECENTRIQ®), avelumab (BAVENCIO®; MSB0010718C), embafolimab (ASC22), durvalumab (IMFINZI®; MEDI-4736), BMS-936559 (MDX1105), cosibelimab (CK-301), lodapolimab (LY3300054), galibrimab (BGB A333), embafolimab (KN035), opucolimab (HLX20), manelimab (BCD135), CX-072, CBT-502 (TQB2450), MSB-2311, SHR-1316, sugemalimab (CS-1001; WBP3155), A167 (KL-A167, HBM9167), STI-A1015 (IMC-001), FAZ-053, BMS-936559 (MDX1105), INCB086550, GEN-104 6 (PD-L1 / 4-1BB), FPT-155 (CTLA4 / PD-L1 / CD28), M7824 (PD-L1 / TGFβ-EC domain), CA-170 (PD-L1 / VISTA), CDX-527 (CD27 / PD-L1), LY-3415244 (TIM-3 / PDL1), INBRX-105 (4-1BB / PDL1), and GNS-1480 (PD-L1 / EGFR).

75. 75. The method of any one of claims 49 to 74, further comprising co-administering an agonist of fms-related receptor tyrosine kinase 3 (FLT3).

76. 76. The method of claim 75, wherein the agonist of FLT3 is selected from GS-3583 and CDX-301.

77. 77. The method of any one of claims 49-76, wherein the magrolimab and the sacituzumab govitecan are administered in a combined synergistic amount.

78. 78. The method of any one of claims 49-77, wherein administration of the magrolimab and the sacituzumab govitecan results in a synergistic effect.

79. 79. The method of claim 78, wherein the synergistic effect is an increase in cancer cell death and / or a decrease in cancer cell growth when comparing the effect of the combination to either the magrolimab or the sacituzumab govitecan alone.

80. 79. The method of claim 78, wherein the synergistic effect is increased phagocytosis of cancer cells by macrophages when comparing the effect of the combination to either the magrolimab or the sacituzumab govitecan alone.

81. 79. The method of claim 78, wherein the synergistic effect is an increase or enhancement in tumor burden reduction when comparing the effect of the combination to either the magrolimab or the sacituzumab govitecan alone.

82. 82. The method of any one of claims 49-81, wherein the magrolimab is administered initially at a priming dose of less than 10 mg / kg, followed by one or more therapeutic doses of at least 15 mg / kg, such as at least 30 mg / kg, 45 mg / kg, 60 mg / kg.

83. 83. The method of any one of claims 49-82, wherein the magrolimab is administered initially at a priming dose of less than 5 mg / kg, followed by one or more therapeutic doses of at least 30 mg / kg, e.g., 45 mg / kg, 60 mg / kg.

84. 84. The method of any one of claims 49-83, wherein the magrolimab is administered initially at a priming dose of 1 mg / kg, then at one or more therapeutic doses of 30 mg / kg, followed by one or more therapeutic doses of 60 mg / kg.

85. 85. The method of any one of claims 49-84, wherein the magrolimab is administered initially at a priming dose of 1 mg / kg, then at one or more therapeutic doses of 20 mg / kg, followed by one or more therapeutic doses of 45 mg / kg.

86. 86. The method of any one of claims 49-85, wherein the magrolimab is administered initially at a priming dose of 1 mg / kg, then at one or more therapeutic doses of 15 mg / kg, followed by one or more therapeutic doses of 30 mg / kg.

87. 87. The method of any one of claims 49-86, wherein the magrolimab is administered intravenously, subcutaneously, or intratumorally.

88. 88. The method of claim 87, wherein the magrolimab is administered intravenously.

89. 89. The method of claim 88, wherein the magrolimab is administered intravenously through an in-line filter.

90. 90. The method of any one of claims 49-89, wherein the sacituzumab govitecan is administered in one or more doses ranging from 3 mg / kg to 18 mg / kg, such as from 8 mg / kg to 10 mg / kg.

91. 91. The method of any one of claims 49-90, wherein the sacituzumab govitecan is administered in one or more doses of 10 mg / kg.

92. 92. The method of any one of claims 49-91, wherein the sacituzumab govitecan is administered intravenously, subcutaneously, or intratumorally.

93. The method of any one of claims 49 to 92, wherein the subject is a human.

94. 94. The method of any one of claims 49-93, wherein the cancer has progressed after at least one previous anti-cancer therapy.

95. 94. The method of any one of claims 49 to 93, wherein the subject is treatment naive.

96. 1. A method of treating, alleviating, reducing, preventing or delaying the growth, proliferation, recurrence or metastasis of triple-negative breast cancer (TNBC) in a subject, comprising administering to the subject effective amounts of: (a) magrolimab; and (b) sacituzumab govitecan.

97. 97. The method of claim 96, wherein the TNBC is (i) unresectable, locally advanced, or (ii) metastatic.

98. 98. The method of any one of claims 96-97, wherein the cancer is unresectable, locally advanced, and the subject is treatment naive.

99. 99. The method of any one of claims 96-98, wherein the treatment results in a reduction in total tumor burden of at least 15%, at least 20%, at least 30%, or at least 40% as determined using a linear bidimensional method (e.g., RECIST v1.1).

100. 100. The method of any one of claims 96 to 99, comprising reducing the size of said metastases or eliminating said metastases.

101. 101. The method of any one of claims 96-100, wherein the cancer does not recur or the tumor mass does not regrow after cessation of treatment.

102. The method of any one of claims 96 to 101, wherein the TNBC has cell surface expression of CD47.

103. 103. The method of any one of claims 96-102, wherein the magrolimab and the sacituzumab govitecan are administered simultaneously.

104. 103. The method of any one of claims 96-102, wherein the magrolimab and the sacituzumab govitecan are administered sequentially.

105. 105. The method of any one of claims 96-104, wherein the magrolimab is administered in a sub-therapeutic dose.

106. 106. The method of any one of claims 96-105, wherein the sacituzumab govitecan is administered at a subtherapeutic dose.

107. 107. The method of any one of claims 96-106, wherein the magrolimab and the sacituzumab govitecan are co-administered at sub-therapeutic doses.

108. 108. The method of any one of claims 96 to 107, further comprising administering a taxane.

109. The method of claim 108, wherein the taxane is selected from paclitaxel, nab-paclitaxel (ABRAXANE®), docetaxel, and cabazitaxel.

110. 110. The method of any one of claims 96 to 109, further comprising administering one or more therapeutic antibodies.

111. 111. The method of any one of claims 96-110, further comprising co-administering one or more blockers or inhibitors of one or more T cell stimulatory immune checkpoint proteins or receptors.

112. 112. The method of claim 111, wherein the one or more immune checkpoint inhibitors comprise a proteinaceous (e.g., antibody) inhibitor of PD-L1 (CD274), PD-1 (PDCD1), or CTLA4.

113. The method of any one of claims 111 to 112, wherein the one or more immune checkpoint proteins or receptors are selected from CD274 (CD274, PDL1, PD-L1) and programmed cell death 1 (PDCD1, PD1, PD-1).

114. The proteinaceous (e.g., antibody) inhibitor of CTLA4 is selected from the group consisting of ipilimumab, tremelimumab, BMS-986218, AGEN1181, AGEN1884 (zalifrelimab), BMS-986249, MK-1308, REGN-4659, ADU-1604, CS-1002, BCD-145, APL-509, JS-007, BA-3071, ONC-392, AGEN-2041, JHL-1155, KN-044, CG-016 1, ATOR-1144, PBI-5D3H5, FPT-155 (CTLA4 / PD-L1 / CD28), PF-06936308 (PD-1 / CTLA4), MGD-019 (PD-1 / CTLA4), KN-046 (PD-1 / CTLA4), MEDI-5752 (CTLA4 / PD-1), XmAb-20717 (PD-1 / CTLA4), and AK-104 (CTLA4 / PD-1).

115. The proteinaceous (e.g., antibody) inhibitor of programmed cell death 1 (PDCD1; NCBI Gene ID: 5133; CD279, PD-1, PD1) is selected from the group consisting of zimberelimab (AB122, GLS-010, WBP-3055), pembrolizumab (KEYTRUDA®, MK-3475, SCH900475), nivolumab (OPDIVO®, BMS-936558, MDX-1106), cemiplimab (LIBTAYO®; cemiplimab-rwlc, REGN-2810), pidilizumab (CT-011), AMG-404, MEDI0680 (AMP-514), spartalisumab (CT-01 ... (PDR001), tislelizumab (BGB-A317), toripalimab (JS-001), genolimuzumab (CBT-501, APL-501, GB226), SHR-1201, camrelizumab (SHR-1210), sintilimab (TYVYT®; IBI-308), dostallimab (TSR-042, WBP-285), lambrolizumab (MK-3475); sasanlimumab (PF-06801591), cetrelimab (JNJ-63723283), serplulimab (HLX-10), retifanlimab (MGA-012), balstilimab (AGEN2034), prorugolimab (BCD 100), budigalimab (ABBV-181), bopratelimab (JTX-4014), AK-103 (HX-008), AK-105, CS-1003, BI-754091, LZM-009, Sym-021, BAT-1306, PD1-PIK, tebotelimab (MGD013; PD-1 / LAG-3), RO-7247669 (PD-1 / LAG-3), FS-118 (LAG-3 / PD-L1), RO-7121661 (PD-1 / TIM-3), RG7769 (PD-1 / TIM-3), PF-06936308 (PD-1 / CTLA4), MGD-019 (PD-1 / CTLA4), KN-046 (PD-1 / CTLA4), XmAb-20717 (PD-1 / CTLA4), AK-104 (CTLA4 / PD-1), and MEDI-5752 (CTLA4 / PD-1).

116. The proteinaceous (e.g., antibody) inhibitor of the CD274 molecule (NCBI Gene ID: Gene ID:29126; B7-H, B7H1, PD-L1) is selected from the group consisting of atezolizumab (TECENTRIQ®), avelumab (BAVENCIO®; MSB0010718C), embafolimab (ASC22), durvalumab (IMFINZI®; MEDI-4736), BMS-936559 (MDX1105), cosibelimab (CK-301), lodapolimab (LY3300054), galibrimab (BGB A333), embafolimab (KN035), opucolimab (HLX20), manelimab (BCD135), CX-072, CBT-502 (TQB2450), MSB-2311, SHR-1316, sugemalimab (CS-1001; WBP3155), A167 (KL-A167, HBM9167), STI-A1015 (IMC-001), FAZ-053, BMS-936559 (MDX1105), INCB086550, GEN-1046 (PD-L1 / 4-1BB), FPT-155 (CTLA4 / PD-L1 / CD28), M7824 (PD-L1 / TGFβ-EC domain), CA-170 (PD-L1 / VISTA), CDX-527 (CD27 / PD-L1), LY-3415244 (TIM-3 / PDL1), INBRX-105 (4-1BB / PDL1), and GNS-1480 (PD-L1 / EGFR).

117. 117. The method of any one of claims 96-116, further comprising co-administering an agonist of fms-related receptor tyrosine kinase 3 (FLT3).

118. 118. The method of claim 117, wherein the agonist of FLT3 is selected from GS-3583 and CDX-301.

119. 119. The method of any one of claims 96-118, wherein the magrolimab and the sacituzumab govitecan are administered in a combined synergistic amount.

120. 120. The method of any one of claims 96-119, wherein administration of the magrolimab and the sacituzumab govitecan results in a synergistic effect.

121. 121. The method of claim 120, wherein the synergistic effect is an increase in cancer cell death and / or a decrease in cancer cell growth when comparing the effect of the combination to either the magrolimab or the sacituzumab govitecan alone.

122. The method of claim 120, wherein the synergistic effect is increased phagocytosis of cancer cells by macrophages when comparing the effect of the combination to either the magrolimab or the sacituzumab govitecan alone.

123. The method of claim 120, wherein the synergistic effect is an increase or enhancement in tumor burden reduction when comparing the effect of the combination to either the magrolimab or the sacituzumab govitecan alone.

124. 124. The method of any one of claims 96-123, wherein the magrolimab is administered initially at a priming dose of less than 10 mg / kg, followed by one or more therapeutic doses of at least 15 mg / kg, such as at least 30 mg / kg, 45 mg / kg, 60 mg / kg.

125. 125. The method of any one of claims 96-124, wherein the magrolimab is administered initially at a priming dose of less than 5 mg / kg, followed by one or more therapeutic doses of at least 30 mg / kg, e.g., 45 mg / kg, 60 mg / kg.

126. 126. The method of any one of claims 96-125, wherein the magrolimab is administered initially at a priming dose of 1 mg / kg, then at one or more therapeutic doses of 30 mg / kg, followed by one or more therapeutic doses of 60 mg / kg.

127. 126. The method of any one of claims 96-125, wherein the magrolimab is administered initially at a priming dose of 1 mg / kg, then at one or more therapeutic doses of 20 mg / kg, followed by one or more therapeutic doses of 45 mg / kg.

128. 126. The method of any one of claims 96-125, wherein the magrolimab is administered initially at a priming dose of 1 mg / kg, then at one or more therapeutic doses of 15 mg / kg, followed by one or more therapeutic doses of 30 mg / kg.

129. 129. The method of any one of claims 96-128, wherein the magrolimab is administered intravenously, subcutaneously, or intratumorally.

130. 130. The method of claim 129, wherein the magrolimab is administered intravenously.

131. 131. The method of claim 130, wherein the magrolimab is administered intravenously through an in-line filter.

132. 132. The method of any one of claims 96-131, wherein the sacituzumab govitecan is administered in one or more doses ranging from 3 mg / kg to 18 mg / kg, for example, from 8 mg / kg to 10 mg / kg.

133. 133. The method of any one of claims 96-132, wherein the sacituzumab govitecan is administered in one or more doses of 10 mg / kg.

134. 134. The method of any one of claims 96-133, wherein the sacituzumab govitecan is administered intravenously, subcutaneously, or intratumorally.

135. the magrolimab and the sacituzumab govitecan are administered in a first 21 day cycle, a second 21 day cycle, and a third 21 day cycle, wherein: a) in said first 21 day cycle, magrolimab is administered at a dose of 1 mg / kg on day 1 and at a dose of 30 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 or 2 and 8; b) in said second 21-day cycle, magrolimab is administered at a dose of 30 mg / kg on days 1, 8, and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8; and c) in the third 21-day cycle, magrolimab is administered at a dose of 60 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8.

136. the magrolimab and the sacituzumab govitecan are administered in a first 21 day cycle, a second 21 day cycle, and a third 21 day cycle, wherein: a) in said first 21 day cycle, magrolimab is administered at a dose of 1 mg / kg on day 1 and at a dose of 20 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 or 2 and day 8; b) in said second 21-day cycle, magrolimab is administered at a dose of 20 mg / kg on days 1, 8, and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8; and c) in the third 21-day cycle, magrolimab is administered at a dose of 45 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8.

137. the magrolimab and the sacituzumab govitecan are administered in a first 21 day cycle, a second 21 day cycle, and a third 21 day cycle, wherein: a) in said first 21 day cycle, magrolimab is administered at a dose of 1 mg / kg on day 1 and at a dose of 15 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 or 2 and day 8; b) in said second 21-day cycle, magrolimab is administered at a dose of 15 mg / kg on days 1, 8, and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8; and c) in the third 21-day cycle, magrolimab is administered at a dose of 30 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8.

138. The method of any one of claims 96 to 137, wherein the subject is a human.

139. The method of any one of claims 96-138, wherein the TNBC has progressed after at least one prior anti-cancer therapy.

140. The method of any one of claims 96 to 138, wherein the subject is treatment naive.

141. 1. A method of treating, alleviating, reducing, preventing or delaying the growth, proliferation, recurrence or metastasis of non-small cell lung cancer (NSCLC) in a subject, comprising administering to the subject effective amounts of: (a) magrolimab; and (b) sacituzumab govitecan.

142. 142. The method of claim 141, wherein the NSCLC is (i) unresectable, locally advanced, or (ii) metastatic.

143. 143. The method of any one of claims 141-142, wherein the cancer is unresectable, locally advanced, and the subject is treatment naive.

144. 144. The method of any one of claims 141-143, wherein the treatment results in a reduction in total tumor burden of at least 15%, at least 20%, at least 30%, or at least 40% as determined using a linear bidimensional method (e.g., RECIST v1.1).

145. 145. A method according to any one of claims 141 to 144, comprising reducing the size of said metastases or eliminating said metastases.

146. 146. The method of any one of claims 141-145, wherein the cancer does not recur or the tumor mass does not regrow after cessation of treatment.

147. The method of any one of claims 141 to 146, wherein the NSCLC has cell surface expression of CD47.

148. 148. The method of any one of claims 141-147, wherein the magrolimab and the sacituzumab govitecan are administered simultaneously.

149. 148. The method of any one of claims 141-147, wherein the magrolimab and the sacituzumab govitecan are administered sequentially.

150. 150. The method of any one of claims 141-149, wherein the magrolimab is administered in a sub-therapeutic dose.

151. 151. The method of any one of claims 141-150, wherein the sacituzumab govitecan is administered at a subtherapeutic dose.

152. 152. The method of any one of claims 141-151, wherein the magrolimab and the sacituzumab govitecan are co-administered at sub-therapeutic doses.

153. 153. The method of any one of claims 141-152, further comprising administering a taxane.

154. 154. The method of claim 153, wherein the taxane is selected from paclitaxel, nab-paclitaxel (ABRAXANE®), docetaxel, and cabazitaxel.

155. 155. The method of any one of claims 141-154, further comprising administering one or more therapeutic antibodies.

156. 156. The method of any one of claims 141-155, further comprising co-administering one or more blockers or inhibitors of one or more T cell stimulatory immune checkpoint proteins or receptors.

157. 157. The method of claim 156, wherein the one or more immune checkpoint inhibitors comprise a proteinaceous (e.g., antibody) inhibitor of PD-L1 (CD274), PD-1 (PDCD1), or CTLA4.

158. 158. The method of any one of claims 156 to 157, wherein the one or more immune checkpoint proteins or receptors are selected from CD274 (CD274, PDL1, PD-L1) and programmed cell death 1 (PDCD1, PD1, PD-1).

159. The proteinaceous (e.g., antibody) inhibitor of CTLA4 is selected from the group consisting of ipilimumab, tremelimumab, BMS-986218, AGEN1181, AGEN1884 (zalifrelimab), BMS-986249, MK-1308, REGN-4659, ADU-1604, CS-1002, BCD-145, APL-509, JS-007, BA-3071, ONC-392, AGEN-2041, JHL-1155, KN-044, CG-016 1, ATOR-1144, PBI-5D3H5, FPT-155 (CTLA4 / PD-L1 / CD28), PF-06936308 (PD-1 / CTLA4), MGD-019 (PD-1 / CTLA4), KN-046 (PD-1 / CTLA4), MEDI-5752 (CTLA4 / PD-1), XmAb-20717 (PD-1 / CTLA4), and AK-104 (CTLA4 / PD-1).

160. The proteinaceous (e.g., antibody) inhibitor of programmed cell death 1 (PDCD1; NCBI Gene ID: 5133; CD279, PD-1, PD1) is selected from the group consisting of zimberelimab (AB122, GLS-010, WBP-3055), pembrolizumab (KEYTRUDA®, MK-3475, SCH900475), nivolumab (OPDIVO®, BMS-936558, MDX-1106), cemiplimab (LIBTAYO®; cemiplimab-rwlc, REGN-2810), pidilizumab (CT-011), AMG-404, MEDI0680 (AMP-514), spartalisumab (CT-01 ... (PDR001), tislelizumab (BGB-A317), toripalimab (JS-001), genolimuzumab (CBT-501, APL-501, GB226), SHR-1201, camrelizumab (SHR-1210), sintilimab (TYVYT®, IBI-308), dostallimab (TSR-042, WBP-285), lambrolizumab (MK-3475); sasanlimumab (PF-06801591), cetrelimab (JNJ-63723283), serplulimab (HLX-10), retifanlimab (MGA-012), balstilimab (AGEN2034), prorugolimab (BCD 100), budigalimab (ABBV-181), bopratelimab (JTX-4014), AK-103 (HX-008), AK-105, CS-1003, BI-754091, LZM-009, Sym-021, BAT-1306, PD1-PIK, tebotelimab (MGD013; PD-1 / LAG-3), RO-7247669 (PD-1 / LAG-3), FS-118 (LAG-3 / PD-L1), RO-7121661 (PD-1 / TIM-3), RG7769 (PD-1 / TIM-3), PF-06936308 (PD-1 / CTLA4), MGD-019 (PD-1 / CTLA4), KN-046 (PD-1 / CTLA4), XmAb-20717 (PD-1 / CTLA4), AK-104 (CTLA4 / PD-1), and MEDI-5752 (CTLA4 / PD-1).

161. The proteinaceous (e.g., antibody) inhibitor of the CD274 molecule (NCBI Gene ID: Gene ID:29126; B7-H, B7H1, PD-L1) is selected from the group consisting of atezolizumab (TECENTRIQ®), avelumab (BAVENCIO®; MSB0010718C), embafolimab (ASC22), durvalumab (IMFINZI®; MEDI-4736), BMS-936559 (MDX1105), cosibelimab (CK-301), lodapolimab (LY3300054), galibrimab (BGB A333), embafolimab (KN035), opucolimab (HLX20), manelimab (BCD135), CX-072, CBT-502 (TQB2450), MSB-2311, SHR-1316, sugemalimab (CS-1001; WBP3155), A167 (KL-A167, HBM9167), STI-A1015 (IMC-001), FAZ-053, BMS-936559 (MDX1105), INCB086550, GEN-1046 (PD-L1 / 4-1BB), FPT-155 (CTLA4 / PD-L1 / CD28), M7824 (PD-L1 / TGFβ-EC domain), CA-170 (PD-L1 / VISTA), CDX-527 (CD27 / PD-L1), LY-3415244 (TIM-3 / PDL1), INBRX-105 (4-1BB / PDL1), and GNS-1480 (PD-L1 / EGFR).

162. 162. The method of any one of claims 141-161, further comprising co-administering an agonist of fms-related receptor tyrosine kinase 3 (FLT3).

163. 163. The method of claim 162, wherein the agonist of FLT3 is selected from GS-3583 and CDX-301.

164. 164. The method of any one of claims 141-163, wherein the magrolimab and the sacituzumab govitecan are administered in a combined synergistic amount.

165. 165. The method of any one of claims 141-164, wherein administration of the magrolimab and the sacituzumab govitecan results in a synergistic effect.

166. The method of claim 165, wherein the synergistic effect is an increase in cancer cell death and / or a decrease in cancer cell growth when comparing the effect of the combination to either the magrolimab or the sacituzumab govitecan alone.

167. The method of claim 165, wherein the synergistic effect is increased phagocytosis of cancer cells by macrophages when comparing the effect of the combination to either the magrolimab or the sacituzumab govitecan alone.

168. The method of claim 165, wherein the synergistic effect is an increase or enhancement in tumor burden reduction when comparing the effect of the combination to either the magrolimab or the sacituzumab govitecan alone.

169. The method of any one of claims 141-168, wherein the magrolimab is administered initially at a priming dose of less than 10 mg / kg, followed by one or more therapeutic doses of at least 15 mg / kg, such as at least 30 mg / kg, 45 mg / kg, 60 mg / kg.

170. The method of any one of claims 141-169, wherein the magrolimab is administered initially at a priming dose of less than 5 mg / kg, followed by one or more therapeutic doses of at least 30 mg / kg, e.g., 45 mg / kg, 60 mg / kg.

171. 171. The method of any one of claims 141-170, wherein the magrolimab is administered initially at a priming dose of 1 mg / kg, then at one or more therapeutic doses of 30 mg / kg, followed by one or more therapeutic doses of 60 mg / kg.

172. 171. The method of any one of claims 141-170, wherein the magrolimab is administered initially at a priming dose of 1 mg / kg, then at one or more therapeutic doses of 20 mg / kg, followed by one or more therapeutic doses of 45 mg / kg.

173. 171. The method of any one of claims 141-170, wherein the magrolimab is administered initially at a priming dose of 1 mg / kg, then at one or more therapeutic doses of 15 mg / kg, followed by one or more therapeutic doses of 30 mg / kg.

174. 174. The method of any one of claims 141-173, wherein the magrolimab is administered intravenously, subcutaneously, or intratumorally.

175. 175. The method of claim 174, wherein the magrolimab is administered intravenously.

176. 176. The method of claim 175, wherein the magrolimab is administered intravenously through an in-line filter.

177. The method of any one of claims 141-176, wherein the sacituzumab govitecan is administered in one or more doses ranging from 3 mg / kg to 18 mg / kg, for example, from 8 mg / kg to 10 mg / kg.

178. 178. The method of any one of claims 141-177, wherein the sacituzumab govitecan is administered in one or more doses of 10 mg / kg.

179. 179. The method of any one of claims 141-178, wherein the sacituzumab govitecan is administered intravenously, subcutaneously, or intratumorally.

180. the magrolimab and the sacituzumab govitecan are administered in a first 21 day cycle, a second 21 day cycle, and a third 21 day cycle, wherein: a) in said first 21 day cycle, magrolimab is administered at a dose of 1 mg / kg on day 1 and at a dose of 30 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 or 2 and 8; b) in said second 21-day cycle, magrolimab is administered at a dose of 30 mg / kg on days 1, 8, and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8; and c) in the third 21-day cycle, magrolimab is administered at a dose of 60 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8.

181. the magrolimab and the sacituzumab govitecan are administered in a first 21 day cycle, a second 21 day cycle, and a third 21 day cycle, wherein: a) in said first 21 day cycle, magrolimab is administered at a dose of 1 mg / kg on day 1 and at a dose of 20 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 or 2 and day 8; b) in said second 21-day cycle, magrolimab is administered at a dose of 20 mg / kg on days 1, 8, and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8; and c) in the third 21-day cycle, magrolimab is administered at a dose of 45 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8.

182. the magrolimab and the sacituzumab govitecan are administered in a first 21 day cycle, a second 21 day cycle, and a third 21 day cycle, wherein: a) in said first 21 day cycle, magrolimab is administered at a dose of 1 mg / kg on day 1 and at a dose of 15 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 or 2 and day 8; b) in said second 21-day cycle, magrolimab is administered at a dose of 15 mg / kg on days 1, 8, and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8; and c) in the third 21-day cycle, magrolimab is administered at a dose of 30 mg / kg on days 8 and 15; and sacituzumab govitecan is administered at a dose of 10 mg / kg on days 1 and 8.

183. The method of any one of claims 141 to 182, wherein the subject is a human.

184. The method of any one of claims 141-183, wherein the NSCLC has progressed after at least one prior anti-cancer therapy.

185. The method of any one of claims 141 to 184, wherein the subject is treatment naive.

186. A kit comprising one or more unit doses of (a) an agent that inhibits the binding between CD47 and SIRPα, and (b) an anti-Trop-2 antibody-drug conjugate (ADC).

187. The kit of claim 186, wherein the agent that inhibits binding between CD47 and SIRPα and the anti-Trop-2 ADC are in separate containers.

188. 188. The kit of claim 187, wherein the separate containers are selected from vials, ampoules, and pre-filled syringes.

189. The kit of any one of claims 186 to 188, wherein the agent that inhibits binding between CD47 and SIRPα comprises an antibody that binds to CD47.

190. The kit of claim 189, wherein the antibody that binds to CD47 is selected from magrolimab, lemzoparlimab, retaplimab, ligufalimab, AO-176, simridarlimab (IBI-322), gentulizumab, ZL-1201, IMC-002, SRF-231, CC-90002 (also known as INBRX-103), NI-1701 (also known as TG-1801) and STI-6643.

191. The kit of any one of claims 186 to 188, wherein the agent that inhibits binding between CD47 and SIRPα comprises an antibody that binds to SIRPα.

192. The kit of claim 191, wherein the antibody that binds to SIRPα is selected from GS-0189 (also known as FSI-189), CC-95251, BI-765063, and APX-700.

193. The kit of any one of claims 186 to 188, wherein the agent that inhibits binding between CD47 and SIRPα comprises a SIRPα-Fc fusion protein.

194. The kit of claim 193, wherein the SIRPα-Fc fusion protein is selected from ALX-148, TTI-621, TTI-622, JMT601 (CPO107), and SL-172154.

195. The kit of any one of claims 186-194, wherein the anti-Trop-2 ADC comprises a topoisomerase I inhibitor.

196. The kit of claim 195, wherein the topoisomerase I inhibitor is selected from irinotecan, topetecan, and SN-38.

197. The kit of any one of claims 186-196, wherein the anti-Trop-2 ADC has the structural formula of mAb-CL2A-SN-38, the structure of which is represented by: 【Chemistry 5】 (For example, as described in US Pat. No. 7,999,083).

198. The kit of any one of claims 186 to 197, wherein the anti-Trop-2 ADC comprises sacituzumab (hRS7; e.g., as described in WO2003074566, Figures 3 and 4).

199. 200. The kit of any one of claims 186-198, wherein the anti-Trop-2 ADC is selected from sacituzumab govitecan, datopotamab deruxtecan (DS-1062), ESG-401, SKB-264, DAC-02, and BAT-8003.

200. The kit of any one of claims 186-199, wherein the anti-Trop-2 ADC comprises sacituzumab govitecan.

201. The kit of any one of claims 186-200, further comprising one or more unit doses of a taxane.

202. The kit of claim 201, wherein the taxane is selected from paclitaxel, nab-paclitaxel (ABRAXANE®), docetaxel, and cabazitaxel.

203. The kit of any one of claims 186 to 202, further comprising one or more therapeutic antibodies.

204. 204. The kit of any one of claims 186 to 203, further comprising one or more blockers or inhibitors of one or more T cell inhibitory immune checkpoint proteins or receptors.

205. 205. The kit of any one of claims 186 to 204, comprising a proteinaceous (e.g., antibody) inhibitor of PD-L1 (CD274), PD-1 (PDCD1) or CTLA4.

206. 206. The kit of any one of claims 204 to 205, comprising a proteinaceous (e.g., antibody) inhibitor of PD-L1 (CD274) or PD-1 (PDCD1).

207. The proteinaceous (e.g., antibody) inhibitor of CTLA4 is selected from the group consisting of ipilimumab, tremelimumab, BMS-986218, AGEN1181, AGEN1884 (zalifrelimab), BMS-986249, MK-1308, REGN-4659, ADU-1604, CS-1002, BCD-145, APL-509, JS-007, BA-3071, ONC-392, AGEN2041, JHL-1155, KN-044, CG-0161 , ATOR-1144, PBI-5D3H5, FPT-155 (CTLA4 / PD-L1 / CD28), PF-06936308 (PD-1 / CTLA4), MGD-019 (PD-1 / CTLA4), KN-046 (PD-1 / CTLA4), MEDI-5752 (CTLA4 / PD-1), XmAb-20717 (PD-1 / CTLA4), and AK-104 (CTLA4 / PD-1).

208. The proteinaceous (e.g., antibody) inhibitor of programmed cell death 1 (PDCD1; NCBI Gene ID: 5133; CD279, PD-1, PD1) is selected from the group consisting of zimberelimab (AB122, GLS-010, WBP-3055), pembrolizumab (KEYTRUDA®, MK-3475, SCH900475), nivolumab (OPDIVO®, BMS-936558, MDX-1106), cemiplimab (LIBTAYO®; cemiplimab-rwlc, REGN-2810), pidilizumab (CT-011), AMG-404, MEDI0680 (AMP-514), spartalisumab (CT-01 ... (PDR001), tislelizumab (BGB-A317), toripalimab (JS-001), genolimuzumab (CBT-501, APL-501, GB226), SHR-1201, camrelizumab (SHR-1210), sintilimab (TYVYT®; IBI-308), dostallimab (TSR-042, WBP-285), lambrolizumab (MK-3475); sasanlimumab (PF-06801591), cetrelimab (JNJ-63723283), serplulimab (HLX-10), retifanlimab (MGA-012), balstilimab (AGEN2034), prorugolimab (BCD 100), budigalimab (ABBV-181), bopratelimab (JTX-4014), AK-103 (HX-008), AK-105, CS-1003, BI-754091, LZM-009, Sym-021, BAT-1306, PD1-PIK, tebotelimab (MGD013; PD-1 / LAG-3), RO-7247669 (PD-1 / LAG-3), FS-118 (LAG-3 / PD-L1), RO-71 21661 (PD-1 / TIM-3), RG7769 (PD-1 / TIM-3), PF-06936308 (PD-1 / CTLA4), MGD-019 (PD-1 / CTLA4), KN-046 (PD-1 / CTLA4), XmAb-20717 (PD-1 / CTLA4), AK-104 (CTLA4 / PD-1), and MEDI-5752 (CTLA4 / PD-1).

209. The proteinaceous (e.g., antibody) inhibitor of the CD274 molecule (NCBI Gene ID: Gene ID:29126; B7-H, B7H1, PD-L1) is selected from the group consisting of atezolizumab (TECENTRIQ®), avelumab (BAVENCIO®; MSB0010718C), embafolimab (ASC22), durvalumab (IMFINZI®; MEDI-4736), BMS-936559 (MDX1105), cosibelimab (CK-301), lodapolimab (LY3300054), galibrimab (BGB A333), embafolimab (KN035), opucolimab (HLX20), manelimab (BCD135), CX-072, CBT-502 (TQB2450), MSB-2311, SHR-1316, sugemalimab (CS-1001; WBP3155), A167 (KL-A167, HBM9167), STI-A1015 (IMC-001), FAZ-053, BMS-936559 (MDX1105), INCB086550, GEN 206. The kit of claim 205, wherein the antibody is selected from the group consisting of -1046 (PD-L1 / 4-1BB), FPT-155 (CTLA4 / PD-L1 / CD28), M7824 (PD-L1 / TGFβ-EC domain), CA-170 (PD-L1 / VISTA), CDX-527 (CD27 / PD-L1), LY-3415244 (TIM-3 / PDL1), INBRX-105 (4-1BB / PDL1), and GNS-1480 (PD-L1 / EGFR).

210. The kit of any one of claims 186 to 209, further comprising co-administering an agonist of fms-related receptor tyrosine kinase 3 (FLT3).

211. The kit of claim 210, wherein the agonist of FLT3 is selected from GS-3583 and CDX-301.

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