Tumor treatment methods using anti-TIGIT antibodies

Abstract

This disclosure relates to a method for treating cancer or the manufacture of a drug for treating cancer by using a pharmaceutical formulation or drug containing an anti-TIGIT monoclonal antibody suitable for co-administration or co-formulation with an anti-PD-L1 monoclonal antibody. This disclosure also relates to a product containing an anti-TIGIT monoclonal antibody or a single dose of both an anti-TIGIT monoclonal antibody and an anti-PD-L1 monoclonal antibody, and to a method for treating cancer using such a product and formulations contained therein.

Description

[Technical Field]

[0001] Cross-reference of related applications This application claims priority and benefits of U.S. Provisional Patent Application No. 63 / 493,691, filed on 31 March 2023, and U.S. Provisional Patent Application No. 63 / 494,982, filed on 07 April 2023, the contents of which are incorporated herein by reference in whole.

[0002] This disclosure relates to the field of treating tumors using anti-TIGIT monoclonal antibodies, either as monotherapy or in combination with anti-PD-L1 monoclonal antibodies.

[0003] Sequence List This disclosure includes a sequence listing submitted electronically in XML format (the full contents thereof are incorporated herein by reference). A copy of the XML was created on 29 March 2024, named 000218-0072-WO1_SL.xml, and has a size of 26,376 bytes. [Background technology]

[0004] Cancer is the leading cause of death worldwide, with approximately 9,958,130 deaths globally in 2020. In North America, an estimated 2,556,860 new cases (1,372,000 men and 1,184,860 women) and 699,274 deaths from cancer. Similar data for Central and Eastern Europe in 2020 showed 1,314,193 new cases (657,259 men and 656,934 women) and 695,828 deaths from cancer (the Global Cancer Observatory, December 2020). For most malignancies, existing therapies are insufficient in improving quality of life, slowing disease progression, extending survival, or curing patients.

[0005] Immunotherapy is an established cancer treatment strategy that has improved the prognosis of many patients suffering from various cancers. Furthermore, the combination of immunotherapies has been shown to be more effective in treating cancer. In fact, the FDA has granted Breakthrough Therapy Designation to the combination of tiragolumab and atezolizumab as a first-line treatment for non-small cell lung cancer. Immunotherapy is typically administered to patients over several hours. Patients receiving combination therapy require two separate infusions, which necessitates longer treatment times (if the therapy is administered on the same day) or more frequent treatments (if the therapy is administered on separate days). In this technology field, there is a need for therapies (including combination therapies) that can be administered more rapidly than intravenous infusion (e.g., subcutaneous injection). [Overview of the Initiative]

[0006] In one embodiment, the present disclosure provides a method for treating cancer, comprising subcutaneously administering an anti-TIGIT monoclonal antibody to a subject in need of cancer treatment, wherein the anti-TIGIT monoclonal antibody is a full-length antibody comprising a heavy-chain variable region including HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, HVR-H2 containing the amino acid sequence of SEQ ID NO: 2, and HVR-H3 containing the amino acid sequence of SEQ ID NO: 3, and a light-chain variable region including HVR-L1 containing the amino acid sequence of SEQ ID NO: 4, HVR-L2 containing the amino acid sequence of SEQ ID NO: 5, and HVR-L3 containing the amino acid sequence of SEQ ID NO: 6.

[0007] In another embodiment, the Disclosure provides the use of approximately 1,000 mg of an anti-TIGIT monoclonal antibody in the manufacture of a drug for treating cancer in a subject requiring cancer treatment, wherein the drug is formulated for subcutaneous administration, and the anti-TIGIT monoclonal antibody is a full-length antibody comprising a heavy-chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3, and a light-chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0008] In another embodiment, the present disclosure provides an anti-TIGIT monoclonal antibody for use in the treatment of cancer in subjects requiring cancer treatment, wherein the anti-TIGIT monoclonal antibody is a full-length antibody comprising a heavy chain variable region including HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, HVR-H2 containing the amino acid sequence of SEQ ID NO: 2, and HVR-H3 containing the amino acid sequence of SEQ ID NO: 3, and a light chain variable region including HVR-L1 containing the amino acid sequence of SEQ ID NO: 4, HVR-L2 containing the amino acid sequence of SEQ ID NO: 5, and HVR-L3 containing the amino acid sequence of SEQ ID NO: 6, and is administered subcutaneously in a dose of approximately 1,000 mg.

[0009] In some embodiments of any of the above, the anti-TIGIT monoclonal antibody is administered to the thigh or abdomen. In some embodiments of any of the above, the anti-TIGIT monoclonal antibody is administered to the thigh. In some embodiments of any of the above, the anti-TIGIT monoclonal antibody is administered to the abdomen. In some embodiments of any of the above, the anti-TIGIT monoclonal antibody is administered every three weeks (Q3W).

[0010] In another embodiment, the Disclosure relates to a method for treating cancer, comprising subcutaneously administering to a subject requiring treatment for cancer a dose of approximately 1,000 mg of an anti-TIGIT monoclonal antibody, and administering to the subject approximately 1,875 mg to approximately 2,000 mg of an anti-PD-L1 monoclonal antibody, wherein the anti-TIGIT monoclonal antibody comprises a heavy chain variable region including HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, HVR-H2 containing the amino acid sequence of SEQ ID NO: 2, and HVR-H3 containing the amino acid sequence of SEQ ID NO: 3, and HVR-L1 containing the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: The present invention provides a method for a full-length antibody comprising a light chain variable region comprising HVR-L2 containing the amino acid sequence of 5 and HVR-L3 containing the amino acid sequence of SEQ ID NO: 6, wherein the anti-PD-L1 monoclonal antibody is a full-length antibody comprising a heavy chain variable region comprising HVR-H1 containing the amino acid sequence of SEQ ID NO: 10, HVR-H2 containing the amino acid sequence of SEQ ID NO: 11, and HVR-H3 containing the amino acid sequence of SEQ ID NO: 12, and a light chain variable region comprising HVR-L1 containing the amino acid sequence of SEQ ID NO: 13, HVR-L2 containing the amino acid sequence of SEQ ID NO: 14, and HVR-L3 containing the amino acid sequence of SEQ ID NO: 15.

[0011] In another embodiment, the Disclosure relates to the use of approximately 1,000 mg of anti-TIGIT monoclonal antibody and approximately 1,875 mg to approximately 2,000 mg of anti-PD-L1 monoclonal antibody in the manufacture of a drug for treating cancer in a subject requiring cancer treatment, wherein the drug is formulated for subcutaneous administration, and the anti-TIGIT monoclonal antibody comprises a heavy chain variable region including HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, HVR-H2 containing the amino acid sequence of SEQ ID NO: 2, and HVR-H3 containing the amino acid sequence of SEQ ID NO: 3, and HVR-L1 containing the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 5 The present invention provides a full-length antibody comprising a light chain variable region comprising HVR-L2 containing an amino acid sequence and HVR-L3 containing the amino acid sequence of SEQ ID NO: 6, wherein the anti-PD-L1 monoclonal antibody is a full-length antibody comprising a heavy chain variable region comprising HVR-H1 containing the amino acid sequence of SEQ ID NO: 10, HVR-H2 containing the amino acid sequence of SEQ ID NO: 11, and HVR-H3 containing the amino acid sequence of SEQ ID NO: 12, and a light chain variable region comprising HVR-L1 containing the amino acid sequence of SEQ ID NO: 13, HVR-L2 containing the amino acid sequence of SEQ ID NO: 14, and HVR-L3 containing the amino acid sequence of SEQ ID NO: 15.

[0012] In another embodiment, the Disclosure relates to an anti-TIGIT monoclonal antibody and an anti-PD-L1 monoclonal antibody for use in the treatment of cancer in a subject requiring cancer treatment, wherein the anti-TIGIT monoclonal antibody is a full-length antibody comprising a heavy chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3, and a light chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6, and is approximately 1.0 The present invention provides an anti-TIGIT monoclonal antibody and an anti-PD-L1 monoclonal antibody, which are administered subcutaneously at a dose of 00 mg, and in which case the anti-PD-L1 monoclonal antibody is a full-length antibody comprising a heavy chain variable region including HVR-H1 containing the amino acid sequence of SEQ ID NO: 10, HVR-H2 containing the amino acid sequence of SEQ ID NO: 11, and HVR-H3 containing the amino acid sequence of SEQ ID NO: 12, and a light chain variable region including HVR-L1 containing the amino acid sequence of SEQ ID NO: 13, HVR-L2 containing the amino acid sequence of SEQ ID NO: 14, and HVR-L3 containing the amino acid sequence of SEQ ID NO: 15, and are administered at a dose of approximately 1,875 mg to approximately 2,000 mg.

[0013] In some embodiments of any of the above, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are administered simultaneously. In some embodiments of any of the above, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are co-formulated. In some embodiments of any of the above, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 24 hours prior to administration to the subject. In some embodiments of any of the above, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed during administration to the subject. In some embodiments of any of the above, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are administered sequentially.

[0014] In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody is administered intravenously. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody is administered subcutaneously.

[0015] In some embodiments of any of the above-described models, the anti-TIGIT monoclonal antibody is administered every three weeks (Q3W).

[0016] In some embodiments of any of the above, cancer is selected from the group consisting of lung cancer, non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, ureteral cancer, urethral cancer, colorectal cancer, colon cancer, rectal cancer, kidney cancer, sarcoma, ovarian cancer, breast cancer, cervical cancer, fallopian tube cancer, endometrial cancer, uterine cancer, pancreatic cancer, gastric cancer, bladder cancer, esophageal cancer, mesothelioma, melanoma, head and neck cancer, thyroid cancer, sarcoma, prostate cancer, penile cancer, glioblastoma, thymic cancer, esophageal cancer, nasopharyngeal cancer, mesothelioma, liver cancer, biliary tract cancer, HPV-positive cancer, leukemia, lymphoma, brain cancer, neuroendocrine cancer, myeloma, mycosis fungoides, Merkel cell carcinoma, hematological malignancies, mismatch repair deficiency (dMMR) cancer, and high-frequency microsatellite instability-H (MSI-H) cancer.

[0017] In some aspects of any of the above embodiments, cancer is bladder cancer, muscle-invasive bladder cancer, urothelial carcinoma, ureteral cancer, urethral cancer, ureteral urothelial carcinoma, urethral urothelial carcinoma, kidney cancer, renal pelvis cancer, renal cell carcinoma, clear cell kidney cancer, rectal cancer, colon cancer, colorectal cancer, sarcoma, osteosarcoma, leiomyosarcoma, pleomorphic sarcoma, myxofibrosarcoma, liposarcoma, chondrosarcoma, lung cancer, non-small cell lung cancer, fallopian tube cancer, peritoneal cancer, esophageal cancer, esophageal squamous cell carcinoma, mesothelial cancer. Cancer, pleural mesothelioma, peritoneal mesothelioma, ovarian cancer, cervical cancer, cervical adenosquamous carcinoma, breast cancer, triple-negative breast cancer, HER2-positive breast cancer, HER2-negative breast cancer, estrogen receptor-positive breast cancer, progesterone receptor-positive breast cancer, luminal type B breast cancer, lymphoma, T-cell lymphoma, B-cell lymphoma, nasal lymphoma, non-Hodgkin lymphoma, follicular lymphoma, penile cancer, prostate cancer, castration-resistant prostate cancer, endometrial cancer, child Cervical cancer, myeloma, multiple myeloma, head and neck cancer, prostate cancer, melanoma, cutaneous melanoma, Merkel cell carcinoma, pancreatic cancer, hepatocellular carcinoma, gastric cancer, gastroesophageal junction adenocarcinoma, glioblastoma, glioblastoma multiforme, mycosis fungoides, HPV-positive cancer, HPV-associated cervical cancer, HPV-associated anal squamous cell carcinoma, HPV-associated penile squamous cell carcinoma, HPV-associated vulvar squamous cell carcinoma, vulvar cancer, vaginal cancer, anal cancer, oropharyngeal cancer, oropharyngeal squamous cell carcinoma, leukemia The following are selected from the group consisting of acute myeloid leukemia, bone cancer, solitary osteoplasmacytoma, squamous cell carcinoma, cutaneous squamous cell carcinoma, thyroid cancer, metastatic colorectal cancer without microsatellite stability / mismatch repair deficiency (MSS / pMMR), mismatch repair deficiency (dMMR) cancer, high microsatellite instability (MSI-H) cancer, nasal extranodal NK / T cell lymphoma, neuroendocrine cancer, biliary tract cancer, cholangiocarcinoma, and intrahepatic cholangiocarcinoma.

[0018] In some embodiments of any of the above, the cancer is selected from the group consisting of Merkel cell carcinoma, urothelial carcinoma, renal cell carcinoma, non-small cell lung cancer, breast cancer, triple-negative breast cancer, hepatocellular carcinoma, melanoma, Hodgkin lymphoma, head and neck cancer, colorectal cancer, gastric cancer, cervical cancer, mediastinal B-cell large lymphoma, cutaneous squamous cell carcinoma, basal cell carcinoma, bladder cancer, endometrial cancer, esophageal cancer, malignant pleural mesothelioma, cancers with high tumor mutation burden (TMB), mismatch repair deficiency (dMMR) cancers, and high microsatellite instability-H (MSI-H) cancers.

[0019] In some embodiments of any of the above, cancer is lung cancer, non-small cell lung cancer, bronchogenic lung cancer, breast cancer, triple-negative breast cancer, estrogen receptor-positive breast cancer, HER2-positive breast cancer, metastatic lobular breast cancer, ductal carcinoma, cervical cancer, fallopian tube cancer, fallopian tube serous adenocarcinoma, ovarian cancer, ovarian endometrioid tumor, ovarian serous adenocarcinoma, ovarian mucinous carcinoma, uterine cancer, endometrial cancer, skin cancer, melanoma, cutaneous melanoma, Merkel cell carcinoma, head and neck cancer, squamous cell carcinoma of the head and neck, hematological malignancies, leukemia, myeloid leukemia Blood cancer, acute myeloid leukemia, chronic lymphocytic leukemia, myelomonocytic leukemia, thyroid cancer, thymic cancer, neuroendocrine cancer, chromaffin cell tumor, glioma, glioblastoma multiforme, paraganglioma, lymphoma, B-cell lymphoma, Hodgkin lymphoma, B-cell non-Hodgkin lymphoma, non-Hodgkin lymphoma, cutaneous T-cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, marginal lymphoma, pancreatic cancer, pancreatic ductal adenocarcinoma, rectal cancer, colon cancer, colorectal cancer, urinary tract cancer, urogenital cancer, mesothelioma, pleural mesothelioma, abdominal Membrane mesothelioma, sarcoma, chondrosarcoma, clear cell sarcoma, liposarcoma, myxoid / round cell liposarcoma, synovial sarcoma, hydatidiform soft part sarcoma, gliosarcoma, uterine carcinosarcoma, kidney cancer, non-clear cell kidney cancer, renal cell carcinoma, bladder cancer, urothelial carcinoma, muscle-invasive bladder cancer, non-muscle-invasive bladder cancer, HER2-positive bladder cancer, gallbladder cancer, stomach cancer, esophageal cancer, esophageal squamous cell carcinoma, gastrointestinal cancer, gastroesophageal cancer, gastroesophageal junction cancer, HER2-positive stomach cancer, primary peritoneal cancer, cutaneous squamous cell carcinoma, prostate cancer, prostate adenocarcinoma, castration-resistant prostate cancer, urinary tract cancer The following group of cancers is selected: genital cancer, ureteral urothelial carcinoma, renal pelvis urothelial carcinoma, urethral urothelial carcinoma, appendiceal cancer, penile cancer, anal canal cancer, hepatocellular carcinoma, hepatobiliary tract cancer, unresectable liver and intrahepatic cholangiocarcinoma, biliary tract cancer, bile duct cancer, intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, HPV-related cancer, HPV-related anal squamous cell carcinoma, HPV-related cervical squamous cell carcinoma, HPV-related penile squamous cell carcinoma, HPV-related vulvar squamous cell carcinoma, nasopharyngeal cancer, nasopharyngeal cancer, pharyngeal squamous cell carcinoma, hypopharyngeal squamous cell carcinoma, oral squamous cell carcinoma, and mycosis fungoides.

[0020] In some embodiments of any of the above, cancer is selected from the group consisting of urothelial carcinoma, non-small cell lung cancer (NSCLC), breast cancer, triple-negative breast cancer, hepatocellular carcinoma, and melanoma. In some embodiments of any of the above, cancer is selected from the group consisting of multiple myeloma, cervical cancer, esophageal cancer, esophageal squamous cell carcinoma, lung cancer, non-small cell lung cancer, glioblastoma, endometrial cancer, ovarian cancer, squamous cell carcinoma, and head and neck cancer. In some embodiments of any of the above, cancer is selected from the group consisting of cervical cancer, head and neck squamous cell carcinoma, head and neck cancer, non-small cell lung cancer, non-squamous non-small cell lung cancer, esophageal squamous cell carcinoma, esophageal cancer, breast cancer, triple-negative breast cancer, gastric cancer, gastroesophageal junction adenocarcinoma, multiple myeloma, non-Hodgkin lymphoma, B-cell lymphoma, liver cancer, bladder cancer, urothelial carcinoma, pancreatic cancer, and pancreatic adenocarcinoma. In some embodiments of any of the above, cancer is a solid tumor. In some embodiments of any of the above-described aspects, the cancer is a blood cancer.

[0021] In some embodiments of any of the above embodiments, the heavy chain variable region of the anti-PD-L1 monoclonal antibody includes the amino acid sequence of SEQ ID NO: 16. In some embodiments of any of the above embodiments, the light chain variable region of the anti-PD-L1 monoclonal antibody includes the amino acid sequence of SEQ ID NO: 17. In some embodiments of any of the above embodiments, the heavy chain variable region of the anti-PD-L1 monoclonal antibody includes the amino acid sequence of SEQ ID NO: 16, and the light chain variable region of the anti-PD-L1 monoclonal antibody includes the amino acid sequence of SEQ ID NO: 17. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody is an IgG antibody. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody is an IgG1 antibody or an IgG4 antibody. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody or anti-TIGIT monoclonal antibody is a human antibody. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody or anti-TIGIT monoclonal antibody is a humanized antibody. In some embodiments of any of the above-described models, the anti-PD-L1 monoclonal antibody is selected from the group consisting of atezolizumab (MPDL3280A), durvalumab (MEDI4736), avelumab, and MDX-1105.

[0022] In some embodiments of any of the above, the heavy chain variable region of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 7 or SEQ ID NO: 8. In some embodiments of any of the above, the light chain variable region of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 9. In some embodiments of any of the above, the heavy chain variable region of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 7 or SEQ ID NO: 8, and the light chain variable region of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 9. In some embodiments of any of the above, the heavy chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24. In some embodiments of any of the above, the heavy chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 19 or SEQ ID NO: 25. In some embodiments of any of the above, the light chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above, the heavy chain of the anti-TIGIT monoclonal antibody contains the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24, and the light chain of the anti-TIGIT monoclonal antibody contains the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above, the heavy chain of the anti-TIGIT monoclonal antibody contains the amino acid sequence of SEQ ID NO: 19 or SEQ ID NO: 25, and the light chain of the anti-TIGIT monoclonal antibody contains the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above, the anti-TIGIT monoclonal antibody is an IgG antibody. In some embodiments of any of the above, the anti-TIGIT monoclonal antibody is an IgG1 antibody or an IgG4 antibody. In some embodiments of any of the above, the anti-TIGIT monoclonal antibody is a human antibody. In some embodiments of any of the above, the anti-TIGIT monoclonal antibody is a humanized antibody. In some embodiments of any of the above, the anti-TIGIT monoclonal antibody inhibits or blocks the interaction between CD226 and TIGIT. In some embodiments of any of the above-described aspects, the anti-TIGIT monoclonal antibody is tiragolumab.

[0023] In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is present in a liquid pharmaceutical composition containing 160 mg / mL of tirzolgomab and 2000 U / mL of hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.5. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are present in a liquid pharmaceutical formulation containing 40 mg / mL of tirzolgomab, 80 mg / ml of atezolizumab, 2000 U / mL of hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.8.

[0024] In another aspect, the present disclosure provides a manufactured product comprising a formulation containing 1,000 mg of tirzolgomab.

[0025] In some embodiments of any of the above aspects, the formulation further comprises 1,875 mg or 2,000 mg of atezolizumab. In certain embodiments, the formulation further comprises 1,875 mg of atezolizumab. In other embodiments, the formulation further comprises 2,000 mg of atezolizumab. In certain embodiments, the formulation further comprises hyaluronidase.

[0026] In another aspect, the present disclosure provides a manufactured product comprising a formulation containing 1,000 mg of tirzolgomab and 1,875 mg or 2,000 mg of atezolizumab. In certain embodiments of the above aspect, the formulation comprises 1,875 mg of atezolizumab. In other embodiments, the formulation comprises 2,000 mg of atezolizumab. In some embodiments, the formulation further comprises hyaluronidase.

[0027] In some embodiments of any of the above embodiments, the concentration of hyaluronidase is 2000 U / mL. In some embodiments of any of the above embodiments, the hyaluronidase is recombinant human hyaluronidase. In some embodiments of any of the above embodiments, the recombinant hyaluronidase is a human soluble pH20 hyaluronidase glycoprotein such as rHuPH20.

[0028] In some embodiments of any of the above embodiments, the product is a vial. In some embodiments of any of the above embodiments, the vial is a single-dose vial. In some embodiments of any of the above embodiments, the vial is capped with a chlorobutyl elastomer stopper.

[0029] In some embodiments of any of the above-described aspects, the product is a pre-filled syringe. In some embodiments of any of the above-described aspects, the product is a syringe pump.

[0030] In some embodiments of any of the above embodiments, the product is a subcutaneous administration device. In some embodiments of any of the above embodiments, the subcutaneous administration device is selected from the group consisting of syringes, syringe pumps, injection devices, drip pumps, syringe pens, needleless devices, auto-injectors, and subcutaneous patch delivery systems.

[0031] In another embodiment, the Disclosure provides a product comprising a subcutaneous administration device, wherein the subcutaneous administration device contains a fixed dose of 1,000 mg of tiragolumab and delivers it to a patient. In some embodiments of this embodiment, the subcutaneous administration device further contains a fixed dose of 1,875 mg or 2,000 mg of atezolizumab and delivers it to a patient. In one embodiment, the subcutaneous administration device further contains a fixed dose of 1,875 mg of atezolizumab and delivers it to a patient. In another embodiment, the subcutaneous administration device further contains a fixed dose of 2,000 mg of atezolizumab and delivers it to a patient. In some embodiments of this embodiment, the subcutaneous administration device further contains hyaluronidase and delivers it to a patient. In one embodiment, the hyaluronidase is a human soluble PH20 hyaluronidase glycoprotein such as rHuPH20.

[0032] In some embodiments of the above-described model, the subcutaneous administration device is selected from the group consisting of syringes, syringe pumps, injection devices, drip pumps, syringe pens, needleless devices, auto-injectors, and subcutaneous patch delivery systems. In one embodiment, the subcutaneous administration device is a syringe. In another embodiment, the subcutaneous administration device is a syringe pump.

[0033] In some embodiments of any of the above embodiments, the product comprises about 3 mL to about 60 mL of anti-TIGIT full-length monoclonal antibody and one or more of hyaluronidase, histidine buffer, sucrose, and polysorbate 20. In some embodiments of any of the above embodiments, the product comprises about 10 mL of tiragolumab and one or more of hyaluronidase, histidine buffer, sucrose, and polysorbate 20. In some embodiments of any of the above embodiments, the product comprises about 7 mL of tiragolumab and one or more of hyaluronidase, histidine buffer, sucrose, and polysorbate 20. In some embodiments of any of the above embodiments, the product comprises about 6.5 mL of tiragolumab and one or more of hyaluronidase, histidine buffer, sucrose, and polysorbate 20. In some embodiments of any of the above-described aspects, the product comprises about 21 mL of tilagolumab and one or more of hyaluronidase, histidine buffer, sucrose, and polysorbate 20. [Brief explanation of the drawing]

[0034] This patent or application file contains at least one drawing created in color. A copy of this patent or patent application publication containing one or more color drawings will be provided by the Patent Office upon request and payment of the required fees.

[0035] [Figure 1] Figure 1 shows a treatment protocol using combination therapy including tiragolumab and atezolizumab. Figure 1 uses the following abbreviations: Atezo = atezolizumab; ECOG = East Coast Cancer Clinical Trials Group; IV = intravenous; PD = progressive disease; PK = pharmacokinetics; PS = performance status; Q3W = every 3 weeks; SC = subcutaneous; TBD = undetermined; Tira = tiragolumab.

[0036] [Figure 2]Figures 2A and 2B show the time-course (day) pharmacokinetic model fit for two representative subjects from Cohort 1A who received a single subcutaneous dose of 880 mg of tiragolumab in the abdomen (Figure 2A), followed by an intravenous dose of 600 mg of tiragolumab, and two representative subjects from Cohort 1B who received a single subcutaneous dose of 880 mg of tiragolumab in the thigh (Figure 2B). Filled circles = directly observed values; solid lines = individual model-predicted concentrations; dashed lines = model-predicted values. [Modes for carrying out the invention]

[0037] general Unless otherwise indicated, the methods disclosed herein, as well as the preparation and use of the compositions, utilize prior art within the scope of the art in molecular biology, biochemistry, chromatin structure and analysis, computational chemistry, cell culture, recombinant DNA, and related fields. These techniques are well described in the literature. For example, see Current Protocols in Molecular Biology or Current Protocols in Immunology, John Wiley & Sons, New York, NY (2009); Ausubel et al., Short Protocols in Molecular Biology, 5th ed., Wiley & Sons, 2002; Sambrook and Russell, Molecular Cloning: A Laboratory Manual (4th Edition, 2012); and other similar literature.

[0038] The term “Specified Version” means the entirety of this disclosure.

[0039] Any embodiment described herein can be combined with one or more other embodiments disclosed herein, including those described in different aspects of this disclosure and different parts of the specification (including embodiments described only in the Examples), unless expressly stated otherwise or deemed inappropriate. The combinations of embodiments are not limited to any specific combination claimed through dependent claims (including multiple dependent claims).

[0040] Any publications, patents, and published patent applications referenced herein are incorporated herein by reference. In the event of any conflict, this specification, including specific definitions, shall prevail.

[0041] Throughout this specification, the word “comprise” or variations such as “comprises” or “comprising” are synonymous with “including,” “containing,” or “characterized by,” and are comprehensive or open-ended, not excluding additional unlisted elements or methods or processes.

[0042] Throughout this specification, when a composition is described as having, containing, or comprising (or a variation thereof) a particular component, it is considered that the composition may or may be essentially composed of or comprise the component mentioned. Similarly, when a method or process is described as having, including, or comprising a particular process step, the process may or may be essentially composed of or comprise the process step mentioned. Furthermore, unless otherwise indicated or the context clearly indicates otherwise, the order of steps or the order in which a particular action is performed is not important, as long as the composition and method described herein are operable. Moreover, two or more steps or actions may be performed simultaneously.

[0043] The term "consists of" excludes elements, processes, or components that are not specifically mentioned.

[0044] The term "essentially derived from" limits the scope of the disclosure to those that do not substantially affect the specific material or process and the fundamental and novel features of the disclosure.

[0045] The example that follows the phrase "e.g." or "for example" is not necessarily exclusive or limiting.

[0046] The articles "a," "an," and "the" are used herein to refer to one or more (i.e., at least one) grammatical objects of the article. For example, "an element" means one or more elements.

[0047] Where used herein, the term “about” modifying quantities of components, parameters, calculations, or measurements of compositions used in the methods of this disclosure means variations in quantities that may occur without substantially affecting the chemical or physical properties of the compositions or methods of this disclosure, for example, due to common measurement and liquid handling procedures used to prepare isolated polypeptides or pharmaceutical compositions in the real world; due to careless errors in these procedures; or due to differences in the manufacture, source, or purity of components used to prepare the compositions or perform the methods. Such variations may be within 5% of a given value or range. The term “about” also includes amounts that differ due to different equilibrium conditions of compositions resulting from a particular initial mixture. Whether modified by the term “about,” the paragraph includes the equivalent of that amount. References to values ​​or parameters marked “about” herein include (and describe) embodiments that apply to that value or parameter itself. For example, a statement referring to “about X” includes a statement of “X.” A numerical range includes the numerical values ​​that define that range.

[0048] As used herein, the term “or” should be understood to mean “and / or” unless the context makes it clear otherwise.

[0049] Although the numerical ranges and parameters representing the broad scope of this disclosure are approximations, the numerical values ​​shown in specific examples are reported as accurately as possible. However, any numerical value inherently contains a certain degree of error that inevitably arises from the standard deviation observed in each test measurement. Furthermore, the numerical descriptions are not limited to the values ​​specifically mentioned, but also include numerical values ​​that a person skilled in the art would ordinarily round to in the context of significant figures. Moreover, all ranges disclosed herein shall be understood to encompass all subranges contained therein. For example, a range described as "1 to 10" should be considered to include all subranges between the minimum value of 1 and the maximum value of 10 (including boundary values), i.e., all subranges starting from a minimum value of 1 or greater, e.g., 1 to 6.1, and ending from a maximum value of 10 or less, e.g., 5.5 to 10. Furthermore, the disclosure of a range shall be considered a disclosure of the endpoint of that range.

[0050] Exemplary methods and materials are described below, but similar or equivalent methods and materials may also be used in the implementation or testing of this disclosure. The materials, methods, and examples are illustrative and not intended to limit the scope.

[0051] definition As used herein, “administering” a substance, compound, drug, or composition to a subject, or “administering” a substance, compound, drug, or composition to a subject, means the contact of the substance, compound, drug, or composition with the subject or with the subject’s cells, tissues, organs, or bodily fluids. Such administration may be carried out using any of the various methods known to those skilled in the art. For example, a substance, compound, drug, or composition may be administered orally or parenterally, such as by injection. In some embodiments, a substance, compound, drug, or composition is administered subcutaneously. In some embodiments, a substance, compound, drug, or composition is administered intravenously. Administration may also be carried out, for example, once, multiple times, and / or over one or more periods of time. In some embodiments, administration includes both direct administration, including self-administration, and indirect administration, including the act of prescribing a drug. For example, as used herein, a physician who instructs a subject to self-administer a drug, or to have another person administer a drug, and / or a physician who provides a subject with a prescription for a drug is administering a drug to the subject.

[0052] As used herein, the terms “antibody” or “Ab” are used in their broadest sense and specifically include monoclonal antibodies (including full-length monoclonal antibodies), polyclonal antibodies, and multispecific antibodies (e.g., bispecific antibodies), and antibody fragments insofar as they exhibit the desired biological activity. “Isolated” antibodies are those identified, separated, and / or recovered from components of their natural environment. Contaminating components of their natural environment are substances that interfere with the study, diagnostic, or therapeutic use of the antibody and may include enzymes, hormones, and other protein-like or non-protein-like solutes. In some embodiments, the antibody is purified to a degree sufficient to obtain at least 15 N-terminal or internal amino acid sequences, for example by using a spinning cup sequencer, or to a degree sufficient to obtain at least 95% by weight of the antibody as determined by the Lowry method, and in some embodiments to a degree sufficient to obtain at least 99% by weight, for example by using a spinning cup sequencer, or to a degree of homogeneity by SDS-PAGE under reducing or non-reducing conditions using Coomassie blue or silver staining. Isolated antibodies include in situ antibodies from recombinant cells because they lack at least one component of the antibody's natural environment. However, isolated antibodies are typically prepared through at least one purification step.

[0053] The terms “anti-TIGIT antibody,” “anti-TIGIT monoclonal antibody,” and “antibody that specifically binds to TIGIT” are used interchangeably herein and refer to antibodies that can bind to TIGIT with sufficient affinity to be useful as diagnostic and / or therapeutic agents for targeting TIGIT. In some embodiments, the degree of binding of the anti-TIGIT antibody to unrelated non-TIGIT proteins is less than about 10% of the antibody's binding to TIGIT, as measured, for example, by radioimmunoassay (RIA). In certain embodiments, the antibody that binds to TIGIT has concentrations of 1 μM, ≤100 nM, ≤10 nM, ≤1 nM, ≤0.1 nM, ≤0.01 nM, or ≤0.001 nM (e.g., 10 -8 M or less, for example, 10 -8 M~10 -13 M, for example, 10-9 M~10 -13 It has a dissociation constant (Kd) of M). In certain embodiments, the anti-TIGIT antibody binds to an epitope on TIGIT that allows for cross-reactivity, such as an epitope of TIGIT that is conserved among different species of TIGIT or an epitope that includes the amino acid residues Ser78, Ser80, and Lys82.

[0054] The terms "anti-PD-L1 antibody", "anti-PD-L1 monoclonal antibody", and "antibody that specifically binds to PD-L1" are used interchangeably herein and refer to an antibody that can bind to PD-L1 with sufficient affinity to be useful as a diagnostic and / or therapeutic agent for targeting PD-L1. In some embodiments, the degree of binding of the anti-PD-L1 antibody to an irrelevant non-PD-L1 protein is less than about 10% of the binding of the antibody to PD-L1, as measured, for example, by radioimmunoassay (RIA). In certain embodiments, the antibody that binds to PD-L1 has a dissociation constant (Kd) of 1 μM, ≤100 nM, ≤10 nM, ≤1 nM, ≤0.1 nM, ≤0.01 nM, or ≤0.001 nM (e.g., 10 -8 M or less, e.g., 10 -8 M~10 -13 M, e.g., 10 -9 M~10 -13 M). In certain embodiments, the anti-PD-L1 antibody binds to an epitope of PD-L1 that is conserved among different species of PD-L1 or an epitope on PD-L1 that allows for cross-reactivity.

[0055] As used herein, the term "atezolizumab" refers to an anti-PD-L1 monoclonal antagonist antibody having the International Nonproprietary Name (INN) in List 112 (WHO Drug Information, Vol. 28, No. 4, 26, 2014, p. 488) or the CAS Registry Number 1380723-44-3.

[0056] As used herein, the term “cancer” refers to a disease caused by the uncontrolled division of abnormal cells in a part of the body. Cancer can be locally progressive or metastatic. In some cases, cancer is locally progressive. In some cases, cancer is metastatic. In some cases, cancer is recurrent. In some cases, cancer can be unresectable (e.g., unresectable locally progressive or metastatic cancer).

[0057] As used herein, the term “chimeric” antibody refers to an antibody in which a portion of the heavy chain and / or light chain originates from a particular source or species, and the remaining portion of the heavy chain and / or light chain originates from a different source or species.

[0058] The terms “full-length antibody,” “intact antibody,” and “whole antibody” are used interchangeably herein and refer to an antibody in substantially complete form, as opposed to an antibody fragment. Specifically, a whole antibody includes antibodies having heavy and light chains containing the Fc region. The constant domain may be the constant domain of the native sequence (e.g., the constant domain of the human native sequence) or an amino acid sequence variant thereof. It is known in the art that C-terminal clipping of antibodies by carboxypeptidases occurs during antibody expression. Such clipped antibodies are considered to be substantially complete and therefore full-length antibodies, despite the removal of one or more C-terminal amino acid residues. In some cases, an intact antibody may have one or more effector functions. In some embodiments, an intact antibody retains all effector functions. Optionally, one or more effector functions of an antibody may be modified or removed.

[0059] As used herein, the term “effector function” refers to a biochemical event resulting from the interaction between the Fc region of an antibody and an Fc receptor or another effector molecule (e.g., an Fc receptor-like (FcRL) molecule, complement component C1q, and tri-element motif-containing protein 21 (TRIM21)). Effector functions include, but are not limited to, antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC). As used herein, the terms “ADCC” or “antibody-dependent cell-mediated cytotoxicity” refer to a cell-mediated reaction in which nonspecific cytotoxic cells expressing FcγR recognize a bound antibody on a target cell, subsequently causing lysis of the target cell. ADCC is correlated with binding to FcγRIIIa, and increased binding to FcγRIIIa increases ADCC activity. As used herein, the terms “ADCP” or “antibody-dependent cell-mediated phagocytosis” refer to a cell-mediated response in which nonspecific cytotoxic cells expressing FcγR recognize bound antibodies on target cells, subsequently causing phagocytosis of the target cells. As used herein, the terms “CDC” or “complement-dependent cell-mediated cytotoxicity” refer to an effector function resulting in the activation of the classical complement pathway, which is triggered by the binding of antibodies to antigens on target cells and activates a cascade of complement-related proteins in the bloodstream.

[0060] As used herein, the term “human antibody” refers to an antibody having an amino acid sequence corresponding to the amino acid sequence of an antibody produced by a human, and / or an antibody produced using any of the techniques known in the art for producing human antibodies. “Human antibody” explicitly excludes humanized antibodies containing non-human antigen-binding residues. Human antibodies can be produced using a variety of techniques known in the art, including phage display libraries, mouse hybridomas, transgenic animals (e.g., mice), and single B-cell techniques. See, for example, Lu et al, J. Biomed. Sci., 27:1 (2020); Hoogenboom and Winter, J. Mol. Biol., 227:381 (1991); and Marks et al., J. Mol. Biol., 222:581 (1991). Each of these references is incorporated herein by reference in whole. Furthermore, the methods described in Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p.77 (1985); Boerner et al., J. Immunol., 147(l):86-95 (1991) can be used for the preparation of human monoclonal antibodies. See also van Dijk and van de Winkel, Curr. Opin. Pharmacol., 5:368-74 (2001). Human antibodies can also be prepared by administering an antigen to transgenic animals (e.g., immunized heterologous mice) that have been modified to produce human antibodies in response to antigen administration (see, for example, U.S. Patents 6,075,181 and 6,150,584 relating to XENOMOUSE® technology). Other transgenic animals for human antibody production are also known in this field, including, for example, HuMAb mice, UntiMAb mice, Transchromo mice, VelocImmune mice, OmniRat, OmniMouse, Harbour Mouse, Kymouse, MeMo mice, and AlivaMab mice.For example, see Bruggemann et al., Arch.Immunol.Ther.Exp.(Warsz.)2015,vol.63(2):101-108. Further techniques are also known in this field. For example, see Li et al., Proc.Natl.Acad.Sci.USA,103:3557-3562(2006) on human antibodies produced by human B cell hybridoma technology.

[0061] As used herein, the term "humanized" antibody refers to a chimeric antibody containing both human and non-human antibody sequences. Typically, a humanized antibody contains a minimal sequence derived from a non-human immunoglobulin. For example, a humanized antibody may include a human immunoglobulin (recipient antibody) in which the hypervariable region residues of the recipient are replaced with hypervariable region residues of a non-human species (donor antibody), such as mouse, rat, rabbit, or non-human primate, possessing the desired specificity, affinity, and capability. In some cases, specific framework region (FR) residues of the human immunoglobulin are replaced with corresponding non-human residues. Furthermore, a humanized antibody may contain residues not found in either the recipient or donor antibody. These modifications are made to further refine antibody performance. Generally, a humanized antibody contains substantially all of at least one, typically two, variable domains, with all or substantially all of the hypervariable loops corresponding to those of a non-human immunoglobulin, and all or substantially all of the FRs being from a human immunoglobulin sequence. Humanized antibodies optionally include the constant region (Fc) of immunoglobulins, typically at least a portion of human immunoglobulins. For further details, see Jones et al, Nature 321:522-525 (1986); Riechmann et al, Nature 332:323-329 (1988); and Presta, Curr. Op. Struct. Biol. 2:593-596 (1992). Also see Vaswani and Hamilton, Ann. Allergy, Asthma & Immunol. 1:105-115 (1998); Harris, Biochem. Soc. Transactions 23:1035-1038 (1995); and Hurle and Gross, Curr. Op. Biotech. 5:428-433 (1994).

[0062] As used herein, the term “hyaluronidase” refers to an enzyme that catalyzes the breakdown of hyaluronic acid (also known as hyaluronan). Hyaluronidase transiently hydrolyzes hyaluronic acid, a component of the subcutaneous matrix, thereby reducing the viscosity of the extracellular matrix of subcutaneous tissue and improving the delivery of subcutaneously administered drugs in the systemic circulation. In some embodiments, the hyaluronidase is recombinant human hyaluronidase. In some embodiments, the recombinant human hyaluronidase is administered subcutaneously.

[0063] As used herein, the terms “hypervariable region,” “HVR,” or “HV” refer to regions of antibody variable domains whose sequences are hypervariable and / or form structurally defined loops. Generally, antibodies contain six HVRs: three in VH (H1, H2, H3) and three in VL (L1, L2, L3). In native antibodies, H3 and L3 exhibit the highest diversity among the six HVRs, and H3 in particular is thought to play a unique role in conferring superior specificity to antibodies. See, for example, Xu et ah, Immunity 13:37-45 (2000); Johnson and Wu, Methods in Molecular Biology 248:1-25 (Lo, ed., Human Press, Totowa, NJ, 2003). For example, naturally occurring camel antibodies consisting only of heavy chains are functional and stable in the absence of light chains. For example, see Hamers-Casterman et al, Nature 363:446-448 (1993); Sheriff et al, Nature Struct. Biol. 3:733-736 (1996).

[0064] Several HVR descriptions are used in the art and are incorporated herein. The Kabat complementarity-determining region (CDR) is based on sequence variability and is one of the most commonly used definitions (Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. (1991)). Chothia, on the other hand, refers to the location of the structural loop (Chothia and Lesk, J. Mol. Biol. 196:901-917 (1987)). AbM HVR represents a compromise between Kabat HVR and Chothia structural loop and is used by Oxford Molecular's AbM antibody modeling software. "Contact" HVR is based on the analysis of available complex crystal structures. The IMGT numbering system was created by considering the high degree of conservation of the V-domain structure and by integrating knowledge gained from the analysis of multiple sources, including literature data on over 5000 sequence alignments, frameworks (FRs), and complementarity-determining regions (CDRs), structural data from X-ray diffraction studies, and characterization of CDR hypervariable loops. The residues derived from each of these HVRs are listed in Table 1 below. [Table 1]

[0065] Unless otherwise specified, HVR is determined according to Kabat et al., as described above. HVR may include “extended HVR” as follows: residues 24–36 or 24–34 (L1), residues 46–56 or 50–56 (L2), and residues 89–97 or 89–96 (L3) in the VL, and residues 26–35 (H1), residues 50–65 or 49–65 (H2), and residues 93–102, 94–102, or 95–102 (H3) in the VH (each based on Kabat numbering).

[0066] As used herein, the term “monoclonal antibody” refers to an antibody obtained from a single cell clone or cell line that produces a substantially homogeneous antibody population. That is, individual antibodies produced by a cell are identical, except for any naturally occurring variations that may be present in small amounts. Monoclonal antibodies are highly specific and target a single antigen. Furthermore, in contrast to polyclonal antibody preparations, which typically contain different antibodies that are directed to different determinants (epitopes), each monoclonal antibody is directed to a single determinant on an antigen. Monoclonal antibodies may be human antibodies, humanized antibodies, or chimeric antibodies.

[0067] The terms “subject” and “patient” are used interchangeably herein and refer to a human being in need of treatment. Therefore, as used herein, the terms “subject” or “patient” mean a human patient or human subject to whom the compositions of this disclosure may be administered. In some embodiments, the subject is in need of treatment for cancer.

[0068] As used herein, the term “effective dose” refers to the minimum amount of a substance, compound, drug, or composition, such as an antibody, required to produce a measurable improvement in a particular disorder. The therapeutically effective dose as used herein may vary depending on factors such as the patient’s disease state, age, sex, and weight, as well as the ability of the substance, compound, drug, or composition, such as an antibody, to induce a desired response in the individual. Appropriate doses and administration regimens may be determined using common techniques of the art. The therapeutically effective dose is also the amount in which the therapeutically beneficial effect outweighs any toxic or adverse effects of the treatment. Beneficial or desired outcomes include clinical results such as a reduction in one or more symptoms caused by the disease, an improvement in the quality of life of the person with the disease, a reduction in the dose of other drugs required to treat the disease, an enhancement of the effect of another drug (e.g., by target), a delay in disease progression, and / or an extension of survival. In the case of cancer or tumors, a therapeutically effective dose of a drug may have the effect of reducing the number of cancer cells, reducing tumor size, inhibiting (i.e., delaying to some extent, or preferably stopping) the invasion of cancer cells into peripheral organs, inhibiting (i.e., delaying to some extent, or preferably stopping) tumor metastasis, inhibiting tumor growth to some extent, alleviating to some extent the symptoms associated with one or more disorders, and / or maintaining remission. A therapeutically effective dose may be administered in one or more doses. For the purposes of this disclosure, a therapeutically effective dose of a drug, compound, or pharmaceutical composition is an amount sufficient to achieve a therapeutic treatment directly or indirectly. As understood in the clinical field, a therapeutically effective dose of a drug, compound, or pharmaceutical composition may or may not be achieved in combination with another drug, compound, or pharmaceutical composition. Thus, “therapeutically effective dose” may be considered in relation to the administration of one or more therapeutic agents, and a monotherapy agent may be considered to be given in a therapeutically effective dose if, in combination with one or more other agents, the desired result can or does not occur.

[0069] As used herein, the term "tiragolumab" refers to the anti-TIGIT monoclonal antagonist antibody as described in WHO Drug Information (International Nonproprietary Names for Pharmaceutical Substances), Proposed INN: List 117, Vol. 31, No. 2, published June 9, 2017 (see page 343). In some embodiments, tiragolumab has CAS registry number 1918185-84-8.

[0070] As used herein, the term “treatment” (and its variations, e.g., “treat” or “treating”) refers to a clinical intervention intended to alter the natural course of the treated individual or cells in the course of clinicopathology. Desired effects of treatment include a reduction in the rate of disease progression, improvement or mitigation of the disease state, prevention of cancer recurrence, prevention of metastasis, and remission or improved prognosis. For example, an individual with cancer is “treated” if one or more cancer-related symptoms are reduced or eliminated, including but not limited to the suppression (or destruction) of cancerous cell proliferation, a reduction in cancer-related symptoms, an improvement in the quality of life of the person with cancer, a reduction in the dosage of other drugs required to treat the cancer, a delay in cancer progression, and / or an extension of the individual’s survival time.

[0071] As used herein, the terms “variable region” or “variable domain” refer to the domains of the heavy or light chain of an antibody that are involved in the antibody’s binding to an antigen. The variable domains of the heavy and light chains of native antibodies (VH and VL, respectively) generally have similar structures, and each domain contains four conserved framework regions (FRs) and three hypervariable regions (HVRs). (See, for example, Kindt et al., Kuby Immunology, 6th ed., WH Freeman and Co., page 91 (2007).) While VH domains are usually paired with VL domains, a single VH or VL domain may be sufficient to confer antigen-binding specificity. Furthermore, antibodies that bind to a specific antigen can be isolated by using the VH or VL domain of the antibody that binds to the antigen and screening a library of complementary VL or VH domains, respectively. For example, see Portolano et al, J.Immunol. 150:880-887 (1993); Clarkson et al, Nature 352:624-628 (1991).

[0072] overview This disclosure relates to a method for treating cancer using an anti-TIGIT full-length monoclonal antibody, either as monotherapy or in combination with an anti-PD-L1 full-length antibody, and to a manufactured product used in such a method.

[0073] Cancer treatment methods In one embodiment, the disclosure provides a method for treating cancer, comprising administering an anti-TIGIT monoclonal antibody to a subject in need of cancer treatment.

[0074] In some embodiments, the method includes administering an anti-TIGIT monoclonal antibody to a subject at a fixed dose of approximately 1,000 mg. In some embodiments, the method includes subcutaneous administration of an anti-TIGIT monoclonal antibody to a subject at a fixed dose of approximately 1,000 mg. In some embodiments, the method includes administering an anti-TIGIT monoclonal antibody to a subject at a fixed dose of approximately 1,000 mg and an anti-PD-L1 monoclonal antibody at a fixed dose of approximately 1,875 mg or approximately 2,000 mg. In some embodiments, the method includes subcutaneous administration of an anti-TIGIT monoclonal antibody to a subject at a fixed dose of approximately 1,000 mg and an anti-PD-L1 monoclonal antibody at a fixed dose of approximately 1,875 mg or approximately 2,000 mg. In some embodiments, the method includes administering an anti-TIGIT monoclonal antibody to a subject at a fixed dose of approximately 1,000 mg and an anti-PD-L1 monoclonal antibody at a fixed dose of approximately 1,875 mg. In some embodiments, the method involves subcutaneously administering to a subject a fixed dose of approximately 1,000 mg of anti-TIGIT monoclonal antibody and approximately 1,875 mg of anti-PD-L1 monoclonal antibody. In some embodiments, the method involves administering to a subject a fixed dose of approximately 1,000 mg of anti-TIGIT monoclonal antibody and approximately 2,000 mg of anti-PD-L1 monoclonal antibody. In some embodiments, the method involves subcutaneously administering to a subject approximately 1,000 mg of anti-TIGIT monoclonal antibody and approximately 2,000 mg of anti-PD-L1 monoclonal antibody.

[0075] In some embodiments, the method includes administering a fixed dose of 1,000 mg of anti-TIGIT monoclonal antibody to a subject. In some embodiments, the method includes subcutaneous administration of a fixed dose of 1,000 mg of anti-TIGIT monoclonal antibody to a subject. In some embodiments, the method includes administering a fixed dose of 1,000 mg of anti-TIGIT monoclonal antibody and a fixed dose of 1,875 mg or 2,000 mg of anti-PD-L1 monoclonal antibody to a subject. In some embodiments, the method includes subcutaneous administration of a fixed dose of 1,000 mg of anti-TIGIT monoclonal antibody and a fixed dose of 1,875 mg or 2,000 mg of anti-PD-L1 monoclonal antibody to a subject. In some embodiments, the method includes administering a fixed dose of 1,000 mg of anti-TIGIT monoclonal antibody and a fixed dose of 1,875 mg of anti-PD-L1 monoclonal antibody to a subject. In some embodiments, the method includes subcutaneous administration of a fixed dose of 1,000 mg of anti-TIGIT monoclonal antibody and a fixed dose of 1,875 mg of anti-PD-L1 monoclonal antibody to a subject. In some embodiments, the method includes administration of a fixed dose of 1,000 mg of anti-TIGIT monoclonal antibody and a fixed dose of 2,000 mg of anti-PD-L1 monoclonal antibody to a subject. In some embodiments, the method includes subcutaneous administration of a fixed dose of 1,000 mg of anti-TIGIT monoclonal antibody and a fixed dose of 2,000 mg of anti-PD-L1 monoclonal antibody to a subject.

[0076] In another embodiment, the present disclosure provides the use of anti-TIGIT monoclonal antibodies in the manufacture of drugs for the treatment of cancer.

[0077] In some embodiments, the drug is configured to deliver a fixed dose of approximately 1,000 mg of anti-TIGIT monoclonal antibody. In some embodiments, the drug is formulated for subcutaneous administration to a subject and is configured to deliver a fixed dose of approximately 1,000 mg of anti-TIGIT monoclonal antibody.

[0078] In some embodiments, the drug is configured to deliver a fixed dose of 1,000 mg of anti-TIGIT monoclonal antibody. In some embodiments, the drug is formulated for subcutaneous administration to a subject and is configured to deliver a fixed dose of 1,000 mg of anti-TIGIT monoclonal antibody.

[0079] In another embodiment, the present disclosure provides the use of anti-TIGIT monoclonal antibodies and anti-PD-L1 antibodies in the manufacture of drugs for the treatment of cancer.

[0080] In some embodiments, the drug is configured to administer a fixed dose of approximately 1,000 mg of anti-TIGIT monoclonal antibody and a fixed dose of approximately 1,875 mg or approximately 2,000 mg of anti-PD-L1 monoclonal antibody. In some embodiments, the drug is formulated for subcutaneous administration to a subject and is configured to administer a fixed dose of approximately 1,000 mg of anti-TIGIT monoclonal antibody and a fixed dose of approximately 1,875 mg or approximately 2,000 mg of anti-PD-L1 monoclonal antibody. In some embodiments, the drug is configured to administer to a subject a fixed dose of approximately 1,000 mg of anti-TIGIT monoclonal antibody and a fixed dose of approximately 1,875 mg of anti-PD-L1 monoclonal antibody. In some embodiments, the drug is formulated for subcutaneous administration to a subject and is configured to administer a fixed dose of approximately 1,000 mg of anti-TIGIT monoclonal antibody and a fixed dose of approximately 1,875 mg of anti-PD-L1 monoclonal antibody. In some embodiments, the drug is configured to administer to a subject a fixed dose of approximately 1,000 mg of anti-TIGIT monoclonal antibody and approximately 2,000 mg of anti-PD-L1 monoclonal antibody. In some embodiments, the drug is formulated for subcutaneous administration to a subject and is configured to administer approximately 1,000 mg of anti-TIGIT monoclonal antibody and approximately 2,000 mg of anti-PD-L1 monoclonal antibody.

[0081] In some embodiments, the drug is configured to administer a fixed dose of 1,000 mg of anti-TIGIT monoclonal antibody and a fixed dose of 1,875 mg or 2,000 mg of anti-PD-L1 monoclonal antibody. In some embodiments, the drug is formulated for subcutaneous administration to a subject and is configured to administer a fixed dose of 1,000 mg of anti-TIGIT monoclonal antibody and a fixed dose of 1,875 mg or 2,000 mg of anti-PD-L1 monoclonal antibody. In some embodiments, the drug is configured to administer a fixed dose of 1,000 mg of anti-TIGIT monoclonal antibody and a fixed dose of 1,875 mg of anti-PD-L1 monoclonal antibody to a subject. In some embodiments, the drug is formulated for subcutaneous administration to a subject and is configured to administer a fixed dose of 1,000 mg of anti-TIGIT monoclonal antibody and a fixed dose of 1,875 mg of anti-PD-L1 monoclonal antibody. In some embodiments, the drug is configured to administer to a subject a fixed dose of 1,000 mg of anti-TIGIT monoclonal antibody and a fixed dose of 2,000 mg of anti-PD-L1 monoclonal antibody. In some embodiments, the drug is formulated for subcutaneous administration to a subject and is configured to administer a fixed dose of 1,000 mg of anti-TIGIT monoclonal antibody and a fixed dose of 2,000 mg of anti-PD-L1 monoclonal antibody.

[0082] In another embodiment, the present disclosure provides an anti-TIGIT monoclonal antibody for use in the treatment of cancer.

[0083] In some embodiments, the anti-TIGIT monoclonal antibody is administered in a fixed dose of approximately 1,000 mg. In some embodiments, the anti-TIGIT monoclonal antibody is administered subcutaneously in a fixed dose of approximately 1,000 mg.

[0084] In some embodiments, the anti-TIGIT monoclonal antibody is administered in a fixed dose of 1,000 mg. In some embodiments, the anti-TIGIT monoclonal antibody is administered subcutaneously in a fixed dose of 1,000 mg.

[0085] In another embodiment, the present disclosure provides anti-TIGIT monoclonal antibodies and anti-PD-L1 antibodies for use in the treatment of cancer.

[0086] In some embodiments, the anti-TIGIT monoclonal antibody is administered at a fixed dose of approximately 1,000 mg, and the anti-PD-L1 monoclonal antibody is administered at a fixed dose of approximately 1,875 mg or approximately 2,000 mg. In some embodiments, the anti-TIGIT monoclonal antibody is administered subcutaneously at a fixed dose of approximately 1,000 mg, and the anti-PD-L1 monoclonal antibody is administered subcutaneously at a fixed dose of approximately 1,875 mg or approximately 2,000 mg. In some embodiments, the anti-TIGIT monoclonal antibody is administered at a fixed dose of approximately 1,000 mg, and the anti-PD-L1 monoclonal antibody is administered at a fixed dose of approximately 1,875 mg. In some embodiments, the anti-TIGIT monoclonal antibody is administered subcutaneously at a fixed dose of approximately 1,000 mg, and the anti-PD-L1 monoclonal antibody is administered subcutaneously at a fixed dose of approximately 1,875 mg. In some embodiments, the anti-TIGIT monoclonal antibody is administered at a fixed dose of approximately 1,000 mg, and the anti-PD-L1 monoclonal antibody is administered at a fixed dose of approximately 2,000 mg.

[0087] In some embodiments, the anti-TIGIT monoclonal antibody is administered at a fixed dose of 1,000 mg, and the anti-PD-L1 monoclonal antibody is administered at a fixed dose of 1,875 mg or 2,000 mg. In some embodiments, the anti-TIGIT monoclonal antibody is administered subcutaneously at a fixed dose of 1,000 mg, and the anti-PD-L1 monoclonal antibody is administered subcutaneously at a fixed dose of 1,875 mg or 2,000 mg. In some embodiments, the anti-TIGIT monoclonal antibody is administered at a fixed dose of 1,000 mg, and the anti-PD-L1 monoclonal antibody is administered at a fixed dose of 1,875 mg. In some embodiments, the anti-TIGIT monoclonal antibody is administered subcutaneously at a fixed dose of 1,000 mg, and the anti-PD-L1 monoclonal antibody is administered subcutaneously at a fixed dose of 1,875 mg. In some embodiments, the anti-TIGIT monoclonal antibody is administered at a fixed dose of 1,000 mg, and the anti-PD-L1 monoclonal antibody is administered at a fixed dose of 2,000 mg.

[0088] In some embodiments of any of the above, the anti-TIGIT monoclonal antibody comprises a heavy chain variable region (VH) comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable region (VL) comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6. In some embodiments of any of the above, the anti-TIGIT monoclonal antibody comprises VH comprising tiragolumab HVR-H1, HVR-H2, and HVR-H3, and VL comprising tiragolumab HVR-L1, HVR-L2, and HVR-L3.

[0089] In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody comprises VH containing the amino acid sequence of SEQ ID NO: 7. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody comprises VL containing the amino acid sequence of SEQ ID NO: 9. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody comprises VH containing the amino acid sequence of SEQ ID NO: 7 and VL containing the amino acid sequence of SEQ ID NO: 9. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody comprises VH of tiragolumab. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody comprises VL of tiragolumab. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody comprises VH and VL of tiragolumab.

[0090] In some embodiments of any of the above embodiments, the heavy chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 18. In some embodiments of any of the above embodiments, the heavy chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 19. In some embodiments of any of the above embodiments, the heavy chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 24. In some embodiments of any of the above embodiments, the heavy chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 25. In some embodiments of any of the above embodiments, the light chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above embodiments, the heavy chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 18, and the light chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above embodiments, the heavy chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 19, and the light chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above, the heavy chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 24, and the light chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above, the heavy chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 25, and the light chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above, the anti-TIGIT monoclonal antibody includes the heavy chain of tiragolumab. In some embodiments of any of the above, the anti-TIGIT monoclonal antibody includes the light chain of tiragolumab. In some embodiments of any of the above, the anti-TIGIT monoclonal antibody includes the heavy and light chains of tiragolumab. In some embodiments of any of the above, the anti-TIGIT monoclonal antibody is tiragolumab.Tiragolumab refers to the anti-TIGIT monoclonal antagonist antibody listed in WHO Drug Information (International Nonproprietary Names for Pharmaceutical Substances), Proposed INN: List 117, Vol. 31, No. 2, published June 9, 2017 (see page 343). In some embodiments of any of the above, tiragolumab has CAS registry number 1918185-84-8.

[0091] In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody is an IgG antibody. The anti-TIGIT monoclonal antibody may be an IgG1 antibody, an IgG2 antibody, an IgG3 antibody, or an IgG4 antibody. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody is an IgG1 antibody or an IgG4 antibody. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody is an IgG1 antibody. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody is a wild-type IgG1 antibody. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody includes a human IgG1 Fc region containing one or more amino acid modifications. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody is an IgG4 antibody. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody is a wild-type IgG4 antibody. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody includes a human IgG4 Fc region containing one or more amino acid modifications. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody is an antagonist antibody. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody may have one or more effector functions. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody retains all effector functions. Optionally, one or more effector functions of the anti-TIGIT monoclonal antibody may be modified or removed.

[0092] In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody is a human antibody. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody is a humanized antibody. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody is a full-length antibody. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody is a full-length IgG antibody. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody is a full-length IgG1 antibody. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody is a full-length human IgG1 antibody. The anti-TIGIT monoclonal antibody may be an antibody fragment.

[0093] In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody comprises a heavy chain variable region (VH) comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 10; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 11; and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 12; and a light chain variable region (VL) comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 14; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 15. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody comprises VH comprising atezolizumab HVR-H1, HVR-H2, and HVR-H3, and VL comprising atezolizumab HVR-L1, HVR-L2, and HVR-L3.

[0094] In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody includes a heavy chain variable region containing the amino acid sequence of SEQ ID NO: 16. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody includes a light chain variable region containing the amino acid sequence of SEQ ID NO: 17. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody includes a heavy chain variable region containing the amino acid sequence of SEQ ID NO: 16 and a light chain variable region containing the amino acid sequence of SEQ ID NO: 17. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody includes atezolizumab VH. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody includes atezolizumab VL. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody includes atezolizumab VH and VL.

[0095] In some embodiments of any of the above embodiments, the heavy chain of the anti-PD-L1 monoclonal antibody includes the amino acid sequence of SEQ ID NO: 21. In some embodiments of any of the above embodiments, the heavy chain of the anti-PD-L1 monoclonal antibody includes the amino acid sequence of SEQ ID NO: 22. In some embodiments of any of the above embodiments, the light chain of the anti-PD-L1 monoclonal antibody includes the amino acid sequence of SEQ ID NO: 23. In some embodiments of any of the above embodiments, the heavy chain of the anti-PD-L1 monoclonal antibody includes the amino acid sequence of SEQ ID NO: 21, and the light chain of the anti-PD-L1 monoclonal antibody includes the amino acid sequence of SEQ ID NO: 23. In some embodiments of any of the above embodiments, the heavy chain of the anti-PD-L1 monoclonal antibody includes the amino acid sequence of SEQ ID NO: 22, and the light chain of the anti-PD-L1 monoclonal antibody includes the amino acid sequence of SEQ ID NO: 23. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody includes the heavy chain of atezolizumab. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody includes the light chain of atezolizumab. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody comprises the heavy and light chains of atezolizumab. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody is atezolizumab.

[0096] In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody is an IgG antibody. The anti-PD-L1 monoclonal antibody may be an IgG1 antibody, an IgG2 antibody, an IgG3 antibody, or an IgG4 antibody. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody is an IgG1 antibody or an IgG4 antibody. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody is an IgG1 antibody. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody is an IgG4 antibody. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody is an antagonist antibody. In some cases, the anti-PD-L1 monoclonal antibody may have one or more effector functions. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody retains all effector functions. Optionally, one or more effector functions of the anti-PD-L1 monoclonal antibody may be modified or removed.

[0097] In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody is a human antibody. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody is a humanized antibody. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody is a full-length antibody. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody is a full-length IgG antibody. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody is a full-length IgG1 antibody. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody is a full-length human IgG1 antibody. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody is a full-length humanized IgG1 antibody. The anti-PD-L1 monoclonal antibody may be an antibody fragment. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody is atezolizumab, which is marketed as TECENTRIQ®. Atezolizumab is listed in WHO Drug Information (International Nonproprietary Names for Pharmaceutical Substances), Proposed INN: List 112, Vol. 28, No. 4, 2014 (see page 488). In some embodiments of any of the above, atezolizumab has CAS registry number 1380723-44-3.

[0098] In some embodiments, the method includes administering a fixed dose of approximately 1,000 mg of tiragolumab to a subject. In some embodiments, the method includes subcutaneous administration of a fixed dose of approximately 1,000 mg of tiragolumab to a subject. In some embodiments, the method includes administering a fixed dose of approximately 1,000 mg of tiragolumab and a fixed dose of approximately 1,875 mg or 2,000 mg of atezolizumab to a subject. In some embodiments, the method includes subcutaneous administration of a fixed dose of approximately 1,000 mg of tiragolumab and a fixed dose of approximately 1,875 mg or 2,000 mg of atezolizumab to a subject. In some embodiments, the method includes administering a fixed dose of approximately 1,000 mg of tiragolumab and a fixed dose of approximately 1,875 mg of atezolizumab to a subject. In some embodiments, the method involves subcutaneously administering to a subject a fixed dose of approximately 1,000 mg of tiragolumab and a fixed dose of atezolizumab. In some embodiments, the method involves administering to a subject a fixed dose of approximately 1,000 mg of tiragolumab and a fixed dose of approximately 2,000 mg of atezolizumab. In some embodiments, the method involves subcutaneously administering to a subject a fixed dose of approximately 1,000 mg of tiragolumab and a fixed dose of approximately 2,000 mg of atezolizumab.

[0099] In some embodiments, the method includes administering a fixed dose of 1,000 mg of tiragolumab to a subject. In some embodiments, the method includes subcutaneous administration of a fixed dose of 1,000 mg of tiragolumab to a subject. In some embodiments, the method includes administering a fixed dose of 1,000 mg of tiragolumab and a fixed dose of 1,875 mg or 2,000 mg of atezolizumab to a subject. In some embodiments, the method includes subcutaneous administration of a fixed dose of 1,000 mg of tiragolumab and a fixed dose of 1,875 mg or 2,000 mg of atezolizumab to a subject. In some embodiments, the method includes administering a fixed dose of 1,000 mg of tiragolumab and a fixed dose of 1,875 mg of atezolizumab to a subject. In some embodiments, the method includes subcutaneous administration of a fixed dose of 1,000 mg of tiragolumab and a fixed dose of 1,875 mg of atezolizumab to a subject. In some embodiments, the method includes administration of a fixed dose of 1,000 mg of tiragolumab and a fixed dose of 2,000 mg of atezolizumab to a subject. In some embodiments, the method includes subcutaneous administration of a fixed dose of 1,000 mg of tiragolumab and a fixed dose of 2,000 mg of atezolizumab to a subject.

[0100] In some embodiments, the drug is configured to administer a fixed dose of approximately 1,000 mg of tiragolumab. In some embodiments, the drug is formulated for subcutaneous administration to a subject and is configured to administer a fixed dose of approximately 1,000 mg of tiragolumab. In some embodiments, the drug is configured to administer a fixed dose of approximately 1,000 mg of tiragolumab and a fixed dose of approximately 1,875 mg or approximately 2,000 mg of atezolizumab. In some embodiments, the drug is formulated for subcutaneous administration to a subject and is configured to administer a fixed dose of approximately 1,000 mg of tiragolumab and a fixed dose of approximately 1,875 mg or approximately 2,000 mg of atezolizumab. In some embodiments, the drug is configured to administer to a subject a fixed dose of approximately 1,000 mg of tiragolumab and a fixed dose of approximately 1,875 mg of atezolizumab. In some embodiments, the drug is formulated for subcutaneous administration to a subject and is configured to deliver approximately 1,000 mg of fixed-dose tiragolumab and approximately 1,875 mg of fixed-dose atezolizumab. In some embodiments, the drug is configured to deliver approximately 1,000 mg of fixed-dose anti-TIGIT monoclonal antibody and approximately 2,000 mg of fixed-dose atezolizumab to a subject. In some embodiments, the drug is formulated for subcutaneous administration to a subject and is configured to deliver approximately 1,000 mg of fixed-dose tiragolumab and approximately 2,000 mg of fixed-dose atezolizumab.

[0101] In some embodiments, the drug is configured to administer a fixed dose of 1,000 mg of tiragolumab. In some embodiments, the drug is formulated for subcutaneous administration to a subject and is configured to administer a fixed dose of 1,000 mg of tiragolumab. In some embodiments, the drug is configured to administer a fixed dose of 1,000 mg of tiragolumab and a fixed dose of 1,875 mg or 2,000 mg of atezolizumab. In some embodiments, the drug is formulated for subcutaneous administration to a subject and is configured to administer a fixed dose of 1,000 mg of tiragolumab and a fixed dose of 1,875 mg or 2,000 mg of atezolizumab. In some embodiments, the drug is configured to administer a fixed dose of 1,000 mg of tiragolumab and a fixed dose of 1,875 mg of atezolizumab to a subject. In some embodiments, the drug is formulated for subcutaneous administration to a subject and is configured to administer a fixed dose of 1,000 mg of tiragolumab and a fixed dose of 1,875 mg of atezolizumab. In some embodiments, the drug is configured to administer a fixed dose of 1,000 mg of anti-TIGIT monoclonal antibody and a fixed dose of 2,000 mg of atezolizumab to a subject. In some embodiments, the drug is formulated for subcutaneous administration to a subject and is configured to administer a fixed dose of 1,000 mg of tiragolumab and a fixed dose of 2,000 mg of atezolizumab.

[0102] In some embodiments, tiragolumab is administered in a fixed dose of approximately 1,000 mg. In some embodiments, tiragolumab is administered subcutaneously in a fixed dose of approximately 1,000 mg. In some embodiments, tiragolumab is administered in a fixed dose of approximately 1,000 mg, and atezolizumab is administered in a fixed dose of approximately 1,875 mg or approximately 2,000 mg. In some embodiments, tiragolumab is administered subcutaneously in a fixed dose of approximately 1,000 mg, and atezolizumab is administered subcutaneously in a fixed dose of approximately 1,875 mg or approximately 2,000 mg. In some embodiments, tiragolumab is administered in a fixed dose of approximately 1,000 mg, and atezolizumab is administered in a fixed dose of approximately 1,875 mg. In some embodiments, tiragolumab is administered subcutaneously at a fixed dose of approximately 1,000 mg, and atezolizumab is administered subcutaneously at a fixed dose of approximately 1,875 mg. In some embodiments, tiragolumab is administered at a fixed dose of approximately 1,000 mg, and atezolizumab is administered at a fixed dose of approximately 2,000 mg. In some embodiments, tiragolumab is administered subcutaneously at a fixed dose of approximately 1,000 mg, and atezolizumab is administered subcutaneously at a fixed dose of approximately 2,000 mg.

[0103] In some embodiments, tiragolumab is administered in a fixed dose of 1,000 mg. In some embodiments, tiragolumab is administered subcutaneously in a fixed dose of 1,000 mg. In some embodiments, tiragolumab is administered in a fixed dose of 1,000 mg, and atezolizumab is administered in a fixed dose of 1,875 mg or 2,000 mg. In some embodiments, tiragolumab is administered subcutaneously in a fixed dose of 1,000 mg, and atezolizumab is administered subcutaneously in a fixed dose of 1,875 mg or 2,000 mg. In some embodiments, tiragolumab is administered in a fixed dose of 1,000 mg, and atezolizumab is administered in a fixed dose of 1,875 mg. In some embodiments, tiragolumab is administered subcutaneously in a fixed dose of 1,000 mg, and atezolizumab is administered subcutaneously in a fixed dose of 1,875 mg. In some embodiments, tiragolumab is administered at a fixed dose of 1,000 mg, and atezolizumab is administered at a fixed dose of 2,000 mg. In some embodiments, tiragolumab is administered subcutaneously at a fixed dose of 1,000 mg, and atezolizumab is administered subcutaneously at a fixed dose of 2,000 mg.

[0104] In some embodiments of any of the above-described aspects, the anti-TIGIT monoclonal antibody may be administered parenterally. In some embodiments, the anti-TIGIT monoclonal antibody is administered by injection. In some embodiments, the anti-TIGIT monoclonal antibody is administered intravenously or subcutaneously. In some embodiments, the anti-TIGIT monoclonal antibody is administered intravenously. In some embodiments, the anti-TIGIT monoclonal antibody is administered subcutaneously.

[0105] In some embodiments of any of the above-described aspects, the anti-PD-L1 monoclonal antibody may be administered parenterally. In some embodiments, the anti-PD-L1 monoclonal antibody is administered by injection. In some embodiments, the anti-PD-L1 monoclonal antibody is administered intravenously or subcutaneously. In some embodiments, the anti-PD-L1 monoclonal antibody is administered intravenously. In some embodiments, the anti-PD-L1 monoclonal antibody is administered subcutaneously.

[0106] In some embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are co-mixed. In some embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are combined into a single drug.

[0107] In some embodiments of any of the above embodiments, the subject is human. In some embodiments of any of the above embodiments, the subject has not received prior treatment with a checkpoint inhibitor (i.e., is CPI naive). In some embodiments of any of the above embodiments, the subject has not received prior treatment with an anti-PD-L1 monoclonal antibody, an anti-PD-1 antibody, an anti-CTL1-4 antibody, or an anti-TIGIT monoclonal antibody. In some embodiments of any of the above embodiments, the subject has not received prior treatment with an anti-PD-L1 monoclonal antibody. In some embodiments of any of the above embodiments, the subject has not received prior treatment with an anti-PD-1 antibody. In some embodiments of any of the above embodiments, the subject has not received prior treatment with an anti-CTL1-4 antibody. In some embodiments of any of the above embodiments, the subject has not received prior treatment with an anti-TIGIT monoclonal antibody. In some embodiments of any of the above embodiments, the subject is cancer immunotherapy (CIT) naive (i.e., is CIT naive).

[0108] In some embodiments of any of the above, cancer is selected from the group consisting of lung cancer, non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, ureteral cancer, urethral cancer, colorectal cancer, colon cancer, rectal cancer, kidney cancer, sarcoma, ovarian cancer, breast cancer, cervical cancer, fallopian tube cancer, endometrial cancer, uterine cancer, pancreatic cancer, gastric cancer, bladder cancer, esophageal cancer, mesothelioma, melanoma, head and neck cancer, thyroid cancer, sarcoma, prostate cancer, penile cancer, glioblastoma, thymic cancer, esophageal cancer, nasopharyngeal cancer, mesothelioma, liver cancer, biliary tract cancer, HPV-positive cancer, leukemia, lymphoma, brain cancer, neuroendocrine cancer, myeloma, mycosis fungoides, Merkel cell carcinoma, hematological malignancies, mismatch repair deficiency (dMMR) cancer, and high-frequency microsatellite instability-H cancer. In some embodiments of any of the above, cancer is lung cancer. In some embodiments of any of the above embodiments, the cancer is non-small cell lung cancer. In some embodiments of any of the above embodiments, the cancer is renal cell carcinoma. In some embodiments of any of the above embodiments, the cancer is urothelial carcinoma. In some embodiments of any of the above embodiments, the cancer is ureteral cancer. In some embodiments, the cancer is urethral cancer. In some embodiments of any of the above embodiments, the cancer is colorectal cancer. In some embodiments of any of the above embodiments, the cancer is colon cancer. In some embodiments of any of the above embodiments, the cancer is rectal cancer. In some embodiments of any of the above embodiments, the cancer is kidney cancer. In some embodiments of any of the above embodiments, the cancer is sarcoma. In some embodiments of any of the above embodiments, the cancer is ovarian cancer. In some embodiments of any of the above embodiments, the cancer is breast cancer. In some embodiments of any of the above embodiments, the cancer is cervical cancer. In some embodiments of any of the above embodiments, the cancer is fallopian tube cancer. In some embodiments of any of the above embodiments, the cancer is endometrial cancer. In some embodiments of any of the above embodiments, the cancer is uterine cancer. In some embodiments of any of the above-described aspects, the cancer is pancreatic cancer.In some embodiments of any of the above embodiments, the cancer is stomach cancer. In some embodiments of any of the above embodiments, the cancer is bladder cancer. In some embodiments of any of the above embodiments, the cancer is esophageal cancer. In some embodiments of any of the above embodiments, the cancer is mesothelioma. In some embodiments of any of the above embodiments, the cancer is melanoma. In some embodiments of any of the above embodiments, the cancer is head and neck cancer. In some embodiments of any of the above embodiments, the cancer is thyroid cancer. In some embodiments of any of the above embodiments, the cancer is sarcoma. In some embodiments of any of the above embodiments, the cancer is prostate cancer. In some embodiments of any of the above embodiments, the cancer is penile cancer. In some embodiments of any of the above embodiments, the cancer is glioblastoma. In some embodiments of any of the above embodiments, the cancer is thymic cancer. In some embodiments of any of the above embodiments, the cancer is esophageal cancer. In some embodiments of any of the above embodiments, the cancer is nasopharyngeal cancer. In some embodiments of any of the above embodiments, the cancer is mesothelioma. In some embodiments of any of the above embodiments, the cancer is liver cancer. In some embodiments of any of the above embodiments, the cancer is biliary tract cancer. In some embodiments of any of the above embodiments, the cancer is HPV-positive cancer. In some embodiments of any of the above embodiments, the cancer is leukemia. In some embodiments of any of the above embodiments, the cancer is lymphoma. In some embodiments of any of the above embodiments, the cancer is brain cancer. In some embodiments of any of the above embodiments, the cancer is neuroendocrine cancer. In some embodiments of any of the above embodiments, the cancer is myeloma. In some embodiments of any of the above embodiments, the cancer is mycosis fungoides. In some embodiments of any of the above embodiments, the cancer is Merkel cell carcinoma. In some embodiments of any of the above embodiments, the cancer is hematological malignancy. In some embodiments of any of the above embodiments, the cancer is mismatch repair deficiency (dMMR) cancer.In some embodiments of any of the above-described aspects, the cancer is a high-frequency microsatellite instability (MSI-H) cancer.

[0109] In some aspects of any of the above embodiments, cancer is bladder cancer, muscle-invasive bladder cancer, urothelial carcinoma, ureteral cancer, urethral cancer, ureteral urothelial carcinoma, urethral urothelial carcinoma, kidney cancer, renal pelvis cancer, renal cell carcinoma, clear cell kidney cancer, rectal cancer, colon cancer, colorectal cancer, sarcoma, osteosarcoma, leiomyosarcoma, pleomorphic sarcoma, myxofibrosarcoma, liposarcoma, chondrosarcoma, lung cancer, non-small cell lung cancer, fallopian tube cancer, peritoneal cancer, esophageal cancer, esophageal squamous cell carcinoma, mesothelial cancer. Cancer, pleural mesothelioma, peritoneal mesothelioma, ovarian cancer, cervical cancer, cervical adenosquamous carcinoma, breast cancer, triple-negative breast cancer, HER2-positive breast cancer, HER2-negative breast cancer, estrogen receptor-positive breast cancer, progesterone receptor-positive breast cancer, luminal type B breast cancer, lymphoma, T-cell lymphoma, B-cell lymphoma, nasal lymphoma, non-Hodgkin lymphoma, follicular lymphoma, penile cancer, prostate cancer, castration-resistant prostate cancer, endometrial cancer, child Cervical cancer, myeloma, multiple myeloma, head and neck cancer, prostate cancer, melanoma, cutaneous melanoma, Merkel cell carcinoma, pancreatic cancer, hepatocellular carcinoma, gastric cancer, gastroesophageal junction adenocarcinoma, glioblastoma, glioblastoma multiforme, mycosis fungoides, HPV-positive cancer, HPV-associated cervical cancer, HPV-associated anal squamous cell carcinoma, HPV-associated penile squamous cell carcinoma, HPV-associated vulvar squamous cell carcinoma, vulvar cancer, vaginal cancer, anal cancer, oropharyngeal cancer, oropharyngeal squamous cell carcinoma, leukemia The following are selected from the group consisting of acute myeloid leukemia, bone cancer, solitary osteoplasmacytoma, squamous cell carcinoma, cutaneous squamous cell carcinoma, thyroid cancer, metastatic colorectal cancer without microsatellite stability / mismatch repair deficiency (MSS / pMMR), mismatch repair deficiency (dMMR) cancer, high microsatellite instability (MSI-H) cancer, nasal extranodal NK / T cell lymphoma, neuroendocrine cancer, biliary tract cancer, cholangiocarcinoma, and intrahepatic cholangiocarcinoma.

[0110] In some embodiments of any of the above, breast cancer is triple-negative breast cancer, HER2-positive breast cancer, HER2-negative breast cancer, estrogen receptor-positive breast cancer, progesterone receptor-positive breast cancer, or luminal type B breast cancer.

[0111] In some embodiments of any of the above-described aspects, the lymphoma is a T-cell lymphoma, a B-cell lymphoma, a nasal lymphoma, a non-Hodgkin lymphoma, or a follicular lymphoma.

[0112] In some embodiments of any of the above, the cancer is selected from the group consisting of Merkel cell carcinoma, urothelial carcinoma, renal cell carcinoma, non-small cell lung cancer, breast cancer, triple-negative breast cancer, hepatocellular carcinoma, melanoma, Hodgkin lymphoma, head and neck cancer, colorectal cancer, gastric cancer, cervical cancer, mediastinal B-cell large lymphoma, cutaneous squamous cell carcinoma, basal cell carcinoma, bladder cancer, endometrial cancer, esophageal cancer, malignant pleural mesothelioma, cancers with high tumor mutation burden (TMB), mismatch repair deficiency (dMMR) cancers, and high microsatellite instability-H (MSI-H) cancers.

[0113] In some embodiments of any of the above, cancer is lung cancer, non-small cell lung cancer, bronchogenic lung cancer, breast cancer, triple-negative breast cancer, estrogen receptor-positive breast cancer, HER2-positive breast cancer, metastatic lobular breast cancer, ductal carcinoma, cervical cancer, fallopian tube cancer, fallopian tube serous adenocarcinoma, ovarian cancer, ovarian endometrioid tumor, ovarian serous adenocarcinoma, ovarian mucinous carcinoma, uterine cancer, endometrial cancer, skin cancer, melanoma, cutaneous melanoma, Merkel cell carcinoma, head and neck cancer, squamous cell carcinoma of the head and neck, hematological malignancies, leukemia, myeloid leukemia Blood cancer, acute myeloid leukemia, chronic lymphocytic leukemia, myelomonocytic leukemia, thyroid cancer, thymic cancer, neuroendocrine cancer, chromaffin cell tumor, glioma, glioblastoma multiforme, paraganglioma, lymphoma, B-cell lymphoma, Hodgkin lymphoma, B-cell non-Hodgkin lymphoma, non-Hodgkin lymphoma, cutaneous T-cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, marginal lymphoma, pancreatic cancer, pancreatic ductal adenocarcinoma, rectal cancer, colon cancer, colorectal cancer, urinary tract cancer, urogenital cancer, mesothelioma, pleural mesothelioma, abdominal Membrane mesothelioma, sarcoma, chondrosarcoma, clear cell sarcoma, liposarcoma, myxoid / round cell liposarcoma, synovial sarcoma, hydatidiform soft part sarcoma, gliosarcoma, uterine carcinosarcoma, kidney cancer, non-clear cell kidney cancer, renal cell carcinoma, bladder cancer, urothelial carcinoma, muscle-invasive bladder cancer, non-muscle-invasive bladder cancer, HER2-positive bladder cancer, gallbladder cancer, stomach cancer, esophageal cancer, esophageal squamous cell carcinoma, gastrointestinal cancer, gastroesophageal cancer, gastroesophageal junction cancer, HER2-positive stomach cancer, primary peritoneal cancer, cutaneous squamous cell carcinoma, prostate cancer, prostate adenocarcinoma, castration-resistant prostate cancer, urinary tract cancer The following group of cancers is selected: genital cancer, ureteral urothelial carcinoma, renal pelvis urothelial carcinoma, urethral urothelial carcinoma, appendiceal cancer, penile cancer, anal canal cancer, hepatocellular carcinoma, hepatobiliary tract cancer, unresectable liver and intrahepatic cholangiocarcinoma, biliary tract cancer, bile duct cancer, intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, HPV-related cancer, HPV-related anal squamous cell carcinoma, HPV-related cervical squamous cell carcinoma, HPV-related penile squamous cell carcinoma, HPV-related vulvar squamous cell carcinoma, nasopharyngeal cancer, nasopharyngeal cancer, pharyngeal squamous cell carcinoma, hypopharyngeal squamous cell carcinoma, oral squamous cell carcinoma, and mycosis fungoides.

[0114] In some embodiments of any of the above-described aspects, the cancer is selected from the group consisting of urothelial carcinoma, non-small cell lung cancer (NSCLC), breast cancer, triple-negative breast cancer, hepatocellular carcinoma, and melanoma.

[0115] In some embodiments of any of the above-described aspects, the cancer is selected from the group consisting of multiple myeloma, cervical cancer, esophageal cancer, esophageal squamous cell carcinoma, lung cancer, non-small cell lung cancer, glioblastoma, endometrial cancer, ovarian cancer, squamous cell carcinoma, and head and neck cancer.

[0116] In some embodiments of any of the above, cancer is selected from the group consisting of cervical cancer, head and neck squamous cell carcinoma, head and neck cancer, non-small cell lung cancer, non-squamous non-small cell lung cancer, esophageal squamous cell carcinoma, esophageal cancer, breast cancer, triple-negative breast cancer, gastric cancer, gastroesophageal junction adenocarcinoma, multiple myeloma, non-Hodgkin lymphoma, B-cell lymphoma, liver cancer, bladder cancer, urothelial carcinoma, pancreatic cancer, and pancreatic adenocarcinoma.

[0117] In some embodiments of any of the above embodiments, the cancer is a solid tumor. In some embodiments of any of the above embodiments, the solid tumor is PD-L1 positive. In some embodiments of any of the above embodiments, the solid tumor is a histologically confirmed PD-L1 solid tumor. In some embodiments of any of the above embodiments, the solid tumor is locally advanced, recurrent, or metastatic.

[0118] In some embodiments of any of the above-described aspects, the cancer is a blood cancer.

[0119] In some embodiments of any of the above, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are administered simultaneously. In some embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are co-formulated. In some embodiments of any of the above, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are administered separately.

[0120] In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 24 hours prior to administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 23 hours prior to administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 22 hours prior to administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 21 hours prior to administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 20 hours prior to administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 19 hours prior to administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 18 hours prior to administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 17 hours prior to administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 16 hours prior to administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 15 hours prior to administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 14 hours prior to administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 13 hours prior to administration to the subject.In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 12 hours prior to administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 11 hours prior to administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 10 hours prior to administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 9 hours prior to administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 8 hours prior to administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 7 hours prior to administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 6 hours prior to administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 5 hours prior to administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 4 hours prior to administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 3 hours prior to administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 2 hours prior to administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 1 hour prior to administration to the subject.In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 45 minutes before administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 30 minutes before administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 15 minutes before administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 10 minutes before administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 5 minutes before administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 4 minutes before administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 3 minutes before administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 2 minutes before administration to the subject. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 1 minute before administration to the subject.

[0121] In some embodiments of any of the above-described aspects, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed during administration to the subject.

[0122] In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are administered parenterally. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are administered intravenously or subcutaneously. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are administered intravenously. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are administered subcutaneously.

[0123] In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody is administered in a formulation containing histidine acetate at a concentration of about 15 mM to about 25 mM, sucrose at a concentration of about 200 mM to about 280 mM, polysorbate at a concentration of about 0.04% (w / v) to about 0.08% (w / v), methionine at a concentration of about 5 mM to about 15 mM, and a pH of about 5.3 to about 6.0. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody is administered in a formulation containing about 20 mM histidine acetate, about 240 mM sucrose, about 0.06% (w / v) polysorbate 20, about 10 mM methionine, and a pH of about 5.8. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody is administered in a formulation containing histidine acetate at a concentration of 15 mM to 25 mM, sucrose at a concentration of 200 mM to 280 mM, polysorbate at a concentration of 0.04% (w / v) to 0.08% (w / v), methionine at a concentration of 5 mM to 15 mM, and a pH of 5.3 to 6.0. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody is administered in a formulation containing 20 mM histidine acetate, 240 mM sucrose, 0.06% (w / v) polysorbate 20, 10 mM methionine, and a pH of 5.8.

[0124] In some embodiments of any of the above, the anti-TIGIT monoclonal antibody is present in a liquid pharmaceutical composition containing 160 mg / mL tiragolumab and 2000 U / mL hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.5. In some embodiments, the drug contains 160 mg / mL tiragolumab and 2000 U / mL hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.5.

[0125] In some embodiments of any of the above, the anti-TIGIT monoclonal antibody and anti-PD-L1 are present in a liquid pharmaceutical formulation containing 40 mg / mL tiragolumab, 80 mg / mL atezolizumab, and 2000 U / mL hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.8. In some embodiments, the drug contains 40 mg / mL tiragolumab, 80 mg / mL atezolizumab, and 2000 U / mL hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.8.

[0126] Table 2 shows the sequences of the specific anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody. [Table 2] TIFF2026513259000004.tif239170TIFF2026513259000005.tif188170

[0127] It is known in the art that C-terminal clipping by carboxypeptidases in the culture medium occurs during antibody expression and processing in cell culture. In some cases, only the C-terminal lysine residue of the heavy chain is clipped. In other cases, additional residues may be clipped. The sequences provided herein are also intended to include variants resulting from the manufacturing process, for example, by C-terminal clipping.

[0128] The C-terminal cleavage process is inaccurate, and it is known in the art that further C-terminal residues may be cleaved. Therefore, for each sequence containing C-terminal lysine disclosed herein, a corresponding sequence lacking two C-terminal residues is also considered. In some embodiments, for each sequence containing C-terminal lysine disclosed herein, a corresponding sequence lacking three C-terminal residues is also considered. In some embodiments, for each sequence containing C-terminal lysine disclosed herein, a corresponding sequence lacking four C-terminal residues is also considered. In some embodiments, for each sequence containing C-terminal lysine disclosed herein, a corresponding sequence lacking five C-terminal residues is also considered. In some embodiments, for each sequence containing C-terminal lysine disclosed herein, a corresponding sequence lacking six C-terminal residues is also considered. In some embodiments, for each sequence containing C-terminal lysine disclosed herein, a corresponding sequence lacking seven C-terminal residues is also considered. In some embodiments, for each sequence containing C-terminal lysine disclosed herein, a corresponding sequence lacking eight C-terminal residues is also considered. In some embodiments, for each sequence containing C-terminal lysine disclosed herein, a corresponding sequence lacking nine C-terminal residues is also considered. In some embodiments, for each sequence containing C-terminal lysine disclosed herein, a corresponding sequence that does not contain 10 C-terminal residues is also considered. In some embodiments, for each sequence containing C-terminal lysine disclosed herein, a corresponding sequence that does not contain 11 C-terminal residues is also considered. In some embodiments, for each sequence containing C-terminal lysine disclosed herein, a corresponding sequence that does not contain 12 C-terminal residues is also considered. In some embodiments, for each sequence containing C-terminal lysine disclosed herein, a corresponding sequence that does not contain 13 C-terminal residues is also considered. In some embodiments, for each sequence containing C-terminal lysine disclosed herein, a corresponding sequence that does not contain 14 C-terminal residues is also considered.In some embodiments, for each sequence containing C-terminal lysine disclosed herein, a corresponding sequence that does not contain 15 C-terminal residues is also considered.

[0129] In some embodiments, the anti-TIGIT monoclonal antibody is co-mixed with the anti-PD-L1 monoclonal antibody. In some embodiments, the anti-TIGIT monoclonal antibody is subcutaneously co-mixed with the anti-PD-L1 monoclonal antibody. In some embodiments, the anti-TIGIT monoclonal antibody is co-mixed with the anti-PD-L1 monoclonal antibody in the abdomen. In some embodiments, the anti-TIGIT monoclonal antibody is subcutaneously co-mixed with the anti-PD-L1 monoclonal antibody in the abdomen. In some embodiments, the anti-TIGIT monoclonal antibody is co-mixed with the anti-PD-L1 monoclonal antibody in the thigh. In some embodiments, the anti-TIGIT monoclonal antibody is subcutaneously co-mixed with the anti-PD-L1 monoclonal antibody in the thigh. In some embodiments, the anti-PD-L1 monoclonal antibody is administered simultaneously with the anti-TIGIT monoclonal antibody. In some embodiments, the anti-TIGIT monoclonal and anti-PD-L1 monoclonal antibodies are co-formulated. In some embodiments, intravenous administration of anti-PD-L1 monoclonal antibody is performed following administration of anti-TIGIT monoclonal antibody. In some embodiments, administration of anti-PD-L1 monoclonal antibody is performed before administration of anti-TIGIT monoclonal antibody. In some embodiments, administration of anti-PD-L1 monoclonal antibody is performed following administration of anti-TIGIT monoclonal antibody.

[0130] In some embodiments, the anti-TIGIT monoclonal antibody is administered at a frequency selected from the group consisting of Q1W, Q2W, Q3W, Q4W, Q5W, and Q6W. In some embodiments, the anti-TIGIT monoclonal antibody is administered at a frequency of Q3W in one or more cycles. In some embodiments, the anti-PD-L1 monoclonal antibody is administered at a frequency of Q3W in one or more cycles. In some embodiments, the anti-PD-L1 monoclonal antibody and the anti-TIGIT monoclonal antibody are administered independently at a frequency of Q3W in one or more cycles.

[0131] In some embodiments, 1,000 mg of anti-TIGIT monoclonal antibody is co-mixed or co-formulated with 1,875 mg or 2,000 mg of anti-PD-L1 monoclonal antibody. In some embodiments, 1,000 mg of anti-TIGIT monoclonal antibody is co-mixed with 2,000 mg of anti-PD-L1 monoclonal antibody. In some embodiments, 1,000 mg of anti-TIGIT monoclonal antibody is co-mixed with 1,875 mg of anti-PD-L1 monoclonal antibody. In some embodiments, the co-mixture is administered subcutaneously. In some embodiments, the co-mixture is administered subcutaneously to the thigh. In some embodiments, the co-mixture is administered subcutaneously to the abdomen. In some embodiments, 1,000 mg of anti-TIGIT monoclonal antibody is co-mixed with 2,000 mg of anti-PD-L1 monoclonal antibody and administered subcutaneously to the abdomen of the target. In some embodiments, 1,000 mg of anti-TIGIT monoclonal antibody is co-mixed with 1,875 mg of anti-PD-L1 monoclonal antibody and administered subcutaneously to the abdomen of the subject requiring treatment.

[0132] In some embodiments, 1,200 mg of anti-PD-L1 monoclonal antibody and 600 mg of anti-TIGIT monoclonal antibody are administered intravenously at Q3W following subcutaneous administration of the cocompound. In some embodiments, the intravenous administration of 1,200 mg of anti-PD-L1 monoclonal antibody and 600 mg of anti-TIGIT monoclonal antibody at Q3W begins at cycle 2 (i.e., after one cycle of subcutaneous administration of the cocompound). In some embodiments, the intravenous administration of 1,200 mg of anti-PD-L1 monoclonal antibody and 600 mg of anti-TIGIT monoclonal antibody at Q3W begins at cycle 4 (i.e., after three cycles of subcutaneous administration of the cocompound). In some embodiments, 1,200 mg of anti-PD-L1 monoclonal antibody and 600 mg of anti-TIGIT monoclonal antibody are administered intravenously separately at Q3W. In some embodiments, 2,000 mg of anti-PD-L1 monoclonal antibody and 1,000 mg of anti-TIGIT monoclonal antibody are administered in Q3W, for example, as a combination preparation as described herein. In some embodiments, 2,000 mg of anti-PD-L1 monoclonal antibody and 1,000 mg of anti-TIGIT monoclonal antibody are administered intravenously in Q3W. In some embodiments, 2,000 mg of anti-PD-L1 monoclonal antibody and 1,000 mg of anti-TIGIT monoclonal antibody are administered separately intravenously in Q3W.

[0133] In some embodiments, the liquid pharmaceutical formulations of the Disclosure are administered every three weeks (Q3W). In some embodiments, the liquid pharmaceutical formulations of the Disclosure are administered subcutaneously at a frequency of Q3W. In some embodiments, the liquid pharmaceutical formulations of the Disclosure are administered intravenously at a frequency of Q3W.

[0134] manufactured goods In another embodiment, the Disclosure provides a product comprising a formulation containing 1,000 mg of tiragolumab. In some embodiments, the product comprises 1,000 mg of tiragolumab.

[0135] In some embodiments, the formulation further comprises 1,875 mg or 2,000 mg of atezolizumab. In some embodiments, the formulation further comprises 1,875 mg or 2,000 mg of atezolizumab. In some embodiments, the formulation further comprises 1,875 mg of atezolizumab. In some embodiments, the formulation further comprises 2,000 mg of atezolizumab. In some embodiments, the formulation further comprises 2,000 mg of atezolizumab.

[0136] In some embodiments, the formulation further comprises hyaluronidase. In some embodiments, the hyaluronidase is recombinant human hyaluronidase. In some embodiments, the hyaluronidase is a human soluble pH20 hyaluronidase glycoprotein such as rHuPH20. In some embodiments, the concentration of hyaluronidase is 500 U / mL to 2600 U / mL. In some embodiments, the concentration of hyaluronidase is 1400 U / mL to 2600 U / mL. In some embodiments, the concentration of hyaluronidase is 2000 U / mL.

[0137] In some embodiments, the formulation contains 160 mg / mL of tiragolumab and 2000 U / mL of hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.5. In some embodiments, the solution contains 160 mg / mL of tiragolumab and 2000 U / mL of rHuPH20 in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.5.

[0138] In another embodiment, the Disclosure provides a product comprising a formulation containing 1,000 mg of tiragolumab and 1,875 mg or 2,000 mg of atezolizumab. In some embodiments, the formulation contains 1,000 mg of tiragolumab and 1,875 mg or 2,000 mg of atezolizumab. In some embodiments, the formulation contains 1,000 mg of tiragolumab and 1,875 mg or 2,000 mg of atezolizumab. In some embodiments, the formulation contains 1,000 mg of tiragolumab and 1,875 mg or 2,000 mg of atezolizumab.

[0139] In some embodiments, the formulation contains 1,875 mg of atezolizumab.

[0140] In some embodiments, the formulation contains 2,000 mg of atezolizumab.

[0141] In some embodiments, the formulation further comprises hyaluronidase. In some embodiments, the concentration of hyaluronidase is 2000 U / mL. In some embodiments, the hyaluronidase is recombinant human hyaluronidase. In some embodiments, the recombinant hyaluronidase is a human soluble pH20 hyaluronidase glycoprotein such as rHuPH20.

[0142] In some embodiments of any of the above embodiments, the product is a vial. In some embodiments of any of the above embodiments, the vial is a single-dose vial. In some embodiments of any of the above embodiments, the vial is a 10 cubic centimeter ("10-cc") vial. In some embodiments of any of the above embodiments, the vial is a 15-cc vial. In some embodiments of any of the above embodiments, the vial is a 20-cc vial. In some embodiments of any of the above embodiments, the vial is a 25-cc vial. In some embodiments of any of the above embodiments, the vial is a 30-cc vial. In some embodiments of any of the above embodiments, the vial is a 35-cc vial. In some embodiments of any of the above embodiments, the vial is a 40-cc vial. In some embodiments of any of the above embodiments, the vial is a 45-cc vial. In some embodiments of any of the above embodiments, the vial is a 50-cc vial. In some embodiments of any of the above embodiments, the vial is a glass vial. In some embodiments of any of the above embodiments, the vial is a plastic vial.

[0143] In some embodiments of any of the above embodiments, the vial is capped with a chlorobutyl elastomer stopper. In some embodiments of any of the above embodiments, the stopper is a D21-7S stopper. Without being bound by theory, the D21-7S stopper reduces particle formation in liquid pharmaceutical formulations. In some embodiments of any of the above embodiments, the D21-7S stopper has a thinner stopper septum.

[0144] In some embodiments of any of the above embodiments, the product is a pre-filled syringe. In some embodiments of any of the above embodiments, the pre-filled syringe is a 10-cc pre-filled syringe. In some embodiments of any of the above embodiments, the pre-filled syringe is a 15-cc pre-filled syringe. In some embodiments of any of the above embodiments, the pre-filled syringe is a 20-cc pre-filled syringe. In some embodiments of any of the above embodiments, the pre-filled syringe is a 25-cc pre-filled syringe. In some embodiments of any of the above embodiments, the pre-filled syringe is a 30-cc pre-filled syringe. In some embodiments of any of the above embodiments, the pre-filled syringe is a 35-cc pre-filled syringe. In some embodiments of any of the above embodiments, the pre-filled syringe is a 40-cc pre-filled syringe. In some embodiments of any of the above embodiments, the pre-filled syringe is a 45-cc pre-filled syringe. In some embodiments of any of the above-described aspects, the pre-filled syringe is a 50-cc pre-filled syringe.

[0145] In some embodiments of any of the above embodiments, the product is a syringe pump. In some embodiments of any of the above embodiments, the product is a subcutaneous administration device. In some embodiments of any of the above embodiments, the subcutaneous administration device is selected from the group consisting of syringes, syringe pumps, injection devices, drip pumps, syringe pens, needleless devices, auto-injectors, and subcutaneous patch delivery systems. In some embodiments of any of the above embodiments, the subcutaneous administration device is a syringe. In some embodiments of any of the above embodiments, the subcutaneous administration device is a syringe pump. In some embodiments of any of the above embodiments, the subcutaneous administration device is an injection device. In some embodiments of any of the above embodiments, the subcutaneous administration device is an drip pump. In some embodiments of any of the above embodiments, the subcutaneous administration device is a syringe pen. In some embodiments of any of the above embodiments, the subcutaneous administration device is a needleless device. In some embodiments of any of the above embodiments, the subcutaneous administration device is an auto-injector. In some embodiments of any of the above embodiments, the subcutaneous administration device is a subcutaneous patch delivery system.

[0146] In another embodiment, the Disclosure provides a product comprising a subcutaneous administration device for delivering a fixed dose of 1,000 mg of tiragolumab to a patient. In some embodiments, the subcutaneous administration device contains a fixed dose of 1,000 mg of tiragolumab and delivers it to the patient.

[0147] In some embodiments, the subcutaneous administration device further contains a fixed dose of 1,875 mg or 2,000 mg of atezolizumab and delivers it to the patient. In some embodiments, the subcutaneous administration device further contains a fixed dose of 1,875 mg or 2,000 mg of atezolizumab and delivers it to the patient. In some embodiments, the subcutaneous administration device further contains a fixed dose of 1,875 mg of atezolizumab and delivers it to the patient. In some embodiments, the subcutaneous administration device further contains a fixed dose of 1,875 mg of atezolizumab and delivers it to the patient. In some embodiments, the subcutaneous administration device further contains a fixed dose of 2,000 mg of atezolizumab and delivers it to the patient. In some embodiments, the subcutaneous administration device further contains a fixed dose of 2,000 mg of atezolizumab and delivers it to the patient.

[0148] In some embodiments, the subcutaneous administration device further contains hyaluronidase and delivers it to the patient. In some embodiments, the concentration of hyaluronidase is 2000 U / mL. In some embodiments, the hyaluronidase is recombinant human hyaluronidase. In some embodiments, the hyaluronidase is a human soluble pH20 hyaluronidase glycoprotein such as rHuPH20.

[0149] In some embodiments, the subcutaneous administration device is selected from the group consisting of syringes, syringe pumps, injection devices, drip pumps, syringe pens, needleless devices, auto-injectors, and subcutaneous patch delivery systems. In some embodiments, the subcutaneous administration device is a syringe. In some embodiments, the subcutaneous administration device is a syringe pump. In some embodiments, the subcutaneous administration device is selected from the group consisting of injection devices. In some embodiments, the subcutaneous administration device is selected from the group consisting of drip pumps. In some embodiments, the subcutaneous administration device is selected from the group consisting of syringe pens. In some embodiments, the subcutaneous administration device is selected from the group consisting of needleless devices. In some embodiments, the subcutaneous administration device is selected from the group consisting of auto-injectors. In some embodiments, the subcutaneous administration device is selected from the group consisting of subcutaneous patch delivery systems.

[0150] In some embodiments of any of the above embodiments, the product comprises about 3 mL to about 60 mL of tiragolumab and one or more of hyaluronidase, histidine buffer, sucrose, and polysorbate 20. In some embodiments of any of the above embodiments, the product comprises about 10 mL of tiragolumab and one or more of hyaluronidase, histidine buffer, sucrose, and polysorbate 20. In some embodiments of any of the above embodiments, the product comprises about 7 mL of tiragolumab and one or more of hyaluronidase, histidine buffer, sucrose, and polysorbate 20. In some embodiments of any of the above embodiments, the product comprises about 6.5 mL of tiragolumab and one or more of hyaluronidase, histidine buffer, sucrose, and polysorbate 20. In some embodiments of any of the above-described aspects, the product comprises about 21 mL of tilagolumab and one or more of hyaluronidase, histidine buffer, sucrose, and polysorbate 20.

[0151] In some embodiments of any of the above embodiments, the product contains about 3 mL to about 30 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 3 mL to about 25 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 3 mL to about 20 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 4 mL to about 25 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 4 mL to about 22 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 4 mL to about 20 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 4 mL to about 18 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 4 mL to about 16 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 4 mL to about 14 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 4 mL to about 12 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 4 mL to about 10 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 4 mL to about 8 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 5 mL to about 7 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 5 mL to about 8 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 5 mL to about 10 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 5 mL to about 21 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 5.5 mL to about 7.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 6 mL to about 8 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 6 mL to about 10 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 6 mL to about 12 mL of formulation. In some embodiments of any of the above-described aspects, the manufactured product comprises approximately 8 mL to approximately 12 mL of formulation.In some embodiments of any of the above embodiments, the product contains about 9 mL to about 11 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 15 mL to about 30 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 18 mL to about 30 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 18 mL to about 28 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 18 mL to about 26 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 18 mL to about 24 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 19 mL to about 23 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 20 mL to about 22 mL of formulation.

[0152] In some embodiments of any of the above embodiments, the product contains about 3 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 3.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 4 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 4.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 5 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 5.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 6 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 6.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 7 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 7.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 8 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 8.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 9 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 9.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 10 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 10.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 11 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 11.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 12 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 12.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 13 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 13.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 14 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 14.5 mL of formulation.In some embodiments of any of the above embodiments, the product contains about 15 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 15.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 16 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 16.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 17 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 17.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 18 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 18.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 19 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 19.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 20 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 21 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 22 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 23 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 24 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 25 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 26 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 27 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 28 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 29 mL of formulation. In some embodiments of any of the above embodiments, the product contains about 30 mL of formulation.

[0153] In some embodiments of any of the above embodiments, the product comprises a formulation of 3 mL to 30 mL. In some embodiments of any of the above embodiments, the product comprises a formulation of 3 mL to 25 mL. In some embodiments of any of the above embodiments, the product comprises a formulation of 3 mL to 20 mL. In some embodiments of any of the above embodiments, the product comprises a formulation of 4 mL to 25 mL. In some embodiments of any of the above embodiments, the product comprises a formulation of 4 mL to 22 mL. In some embodiments of any of the above embodiments, the product comprises a formulation of 4 mL to 20 mL. In some embodiments of any of the above embodiments, the product comprises a formulation of 4 mL to 18 mL. In some embodiments of any of the above embodiments, the product comprises a formulation of 4 mL to 16 mL. In some embodiments of any of the above embodiments, the product comprises a formulation of 4 mL to 14 mL. In some embodiments of any of the above embodiments, the product comprises a formulation of 4 mL to 12 mL. In some embodiments of any of the above embodiments, the product comprises a formulation of 4 mL to 10 mL. In some embodiments of any of the above embodiments, the product contains 4 mL to 8 mL of formulation. In some embodiments of any of the above embodiments, the product contains 5 mL to 7 mL of formulation. In some embodiments of any of the above embodiments, the product contains 5 mL to 8 mL of formulation. In some embodiments of any of the above embodiments, the product contains 5 mL to 10 mL of formulation. In some embodiments of any of the above embodiments, the product contains 5 mL to 21 mL of formulation. In some embodiments of any of the above embodiments, the product contains 5.5 mL to 7.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains 6 mL to 8 mL of formulation. In some embodiments of any of the above embodiments, the product contains 6 mL to 10 mL of formulation. In some embodiments of any of the above embodiments, the product contains 6 mL to 12 mL of formulation. In some embodiments of any of the above embodiments, the product contains 8 mL to 12 mL of formulation. In some embodiments of any of the above embodiments, the product contains 9 mL to 11 mL of formulation.In some embodiments of any of the above embodiments, the manufactured product contains 15 mL to 30 mL of formulation. In some embodiments of any of the above embodiments, the manufactured product contains 18 mL to 30 mL of formulation. In some embodiments of any of the above embodiments, the manufactured product contains 18 mL to 28 mL of formulation. In some embodiments of any of the above embodiments, the manufactured product contains 18 mL to 26 mL of formulation. In some embodiments of any of the above embodiments, the manufactured product contains 18 mL to 24 mL of formulation. In some embodiments of any of the above embodiments, the manufactured product contains 19 mL to 23 mL of formulation. In some embodiments of any of the above embodiments, the manufactured product contains 20 mL to 22 mL of formulation.

[0154] In some embodiments of any of the above embodiments, the product contains 3 mL of formulation. In some embodiments of any of the above embodiments, the product contains 3.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains 4 mL of formulation. In some embodiments of any of the above embodiments, the product contains 4.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains 5 mL of formulation. In some embodiments of any of the above embodiments, the product contains 5.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains 6 mL of formulation. In some embodiments of any of the above embodiments, the product contains 6.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains 7 mL of formulation. In some embodiments of any of the above embodiments, the product contains 7.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains 8 mL of formulation. In some embodiments of any of the above embodiments, the product contains 8.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains 9 mL of formulation. In some embodiments of any of the above embodiments, the product contains 9.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains 10 mL of formulation. In some embodiments of any of the above embodiments, the product contains 10.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains 11 mL of formulation. In some embodiments of any of the above embodiments, the product contains 11.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains 12 mL of formulation. In some embodiments of any of the above embodiments, the product contains 12.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains 13 mL of formulation. In some embodiments of any of the above embodiments, the product contains 13.5 mL of formulation. In some embodiments of any of the above embodiments, the product contains 14 mL of formulation. In some embodiments of any of the above embodiments, the product contains 14.5 mL of formulation.In some embodiments of any of the above embodiments, the product comprises 15 mL of formulation. In some embodiments of any of the above embodiments, the product comprises 15.5 mL of formulation. In some embodiments of any of the above embodiments, the product comprises 16 mL of formulation. In some embodiments of any of the above embodiments, the product comprises 16.5 mL of formulation. In some embodiments of any of the above embodiments, the product comprises 17 mL of formulation. In some embodiments of any of the above embodiments, the product comprises 17.5 mL of formulation. In some embodiments of any of the above embodiments, the product comprises 18 mL of formulation. In some embodiments of any of the above embodiments, the product comprises 18.5 mL of formulation. In some embodiments of any of the above embodiments, the product comprises 19 mL of formulation. In some embodiments of any of the above embodiments, the product comprises 19.5 mL of formulation. In some embodiments of any of the above embodiments, the product comprises 20 mL of formulation. In some embodiments of any of the above embodiments, the product comprises 21 mL of formulation. In some embodiments of any of the above embodiments, the product comprises 22 mL of formulation. In some embodiments of any of the above embodiments, the product comprises 23 mL of the formulation. In some embodiments of any of the above embodiments, the product comprises 24 mL of the formulation. In some embodiments of any of the above embodiments, the product comprises 25 mL of the formulation. In some embodiments of any of the above embodiments, the product comprises 26 mL of the formulation. In some embodiments of any of the above embodiments, the product comprises 27 mL of the formulation. In some embodiments of any of the above embodiments, the product comprises 28 mL of the formulation. In some embodiments of any of the above embodiments, the product comprises 29 mL of the formulation. In some embodiments of any of the above embodiments, the product comprises 30 mL of the formulation.

[0155] In another embodiment, the present disclosure relates to a product suitable for subcutaneous injection comprising (a) 1000 mg of anti-TIGIT monoclonal antibody, (b) 1875 mg or 2000 mg of anti-PD-L1 monoclonal antibody, (c) 5 mM to 30 mM histidine buffer, (d) 180 mM to 320 mM sucrose, (e) 0.03% (w / v) to 0.08% (w / v) polysorbate 20, (f) 500 U / mL to 2600 U / mL hyaluronidase, and a pH of approximately 5.2 to 6.1, wherein the anti-TIGIT monoclonal antibody comprises HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, HVR-H2 containing the amino acid sequence of SEQ ID NO: 2, and the amino acid sequence of SEQ ID NO: 3 The provided product comprises a heavy chain variable region containing HVR-H3, and a light chain variable region containing HVR-L1 containing the amino acid sequence of SEQ ID NO: 4, HVR-L2 containing the amino acid sequence of SEQ ID NO: 5, and HVR-L3 containing the amino acid sequence of SEQ ID NO: 6. The anti-PD-L1 monoclonal antibody comprises a heavy chain variable region containing HVR-H1 containing the amino acid sequence of SEQ ID NO: 10, HVR-H2 containing the amino acid sequence of SEQ ID NO: 11, and HVR-H3 containing the amino acid sequence of SEQ ID NO: 12, and a light chain variable region containing HVR-L1 containing the amino acid sequence of SEQ ID NO: 13, HVR-L2 containing the amino acid sequence of SEQ ID NO: 14, and HVR-L3 containing the amino acid sequence of SEQ ID NO: 15. In some embodiments, the product comprises a formulation containing (a) 1000 mg of anti-TIGIT monoclonal antibody, (b) 1875 mg or 2000 mg of anti-PD-L1 monoclonal antibody, (c) 15 mM to 25 mM histidine buffer, (d) 200 mM to 280 mM sucrose, (e) 0.04% (w / v) to 0.08% (w / v) polysorbate 20, (f) 1400 U / mL to 2600 U / mL hyaluronidase, and a pH of approximately 5.5 to 5.8.In some embodiments, the product comprises a formulation suitable for subcutaneous injection containing (a) 1000 mg of anti-TIGIT monoclonal antibody, (b) 1875 mg or 2000 mg of anti-PD-L1 monoclonal antibody, (c) 15 mM to 25 mM histidine buffer, (d) 200 mM to 280 mM sucrose, (e) 0.04% (w / v) to 0.08% (w / v) polysorbate 20, (f) 1400 U / mL to 2600 U / mL hyaluronidase, and a pH of approximately 5.5 to 5.8. In some embodiments, the product comprises a formulation suitable for subcutaneous injection containing (a) 1000 mg of anti-TIGIT monoclonal antibody, (b) 1875 mg of anti-PD-L1 monoclonal antibody, (c) 15 mM to 25 mM histidine buffer, (d) 200 mM to 280 mM sucrose, (e) 0.04% (w / v) to 0.08% (w / v) polysorbate 20, (f) 1400 U / mL to 2600 U / mL hyaluronidase, and a pH of approximately 5.5 to 5.8. In some embodiments, the product comprises a formulation suitable for subcutaneous injection containing (a) 1000 mg of anti-TIGIT monoclonal antibody, (b) 2000 mg of anti-PD-L1 monoclonal antibody, (c) 15 mM to 25 mM histidine buffer, (d) 200 mM to 280 mM sucrose, (e) 0.04% (w / v) to 0.08% (w / v) polysorbate 20, (f) 1400 U / mL to 2600 U / mL hyaluronidase, and a pH of approximately 5.5 to 5.8.

[0156] In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody includes VH containing the amino acid sequence of SEQ ID NO: 7. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody includes VH containing the amino acid sequence of SEQ ID NO: 8. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody includes VL containing the amino acid sequence of SEQ ID NO: 9. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody includes VH containing the amino acid sequence of SEQ ID NO: 7 and VL containing the amino acid sequence of SEQ ID NO: 9. In some embodiments of any of the above embodiments, the heavy chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 18. In some embodiments of any of the above embodiments, the heavy chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 19. In some embodiments of any of the above embodiments, the heavy chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 24. In some embodiments of any of the above embodiments, the heavy chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 25. In some embodiments of any of the above embodiments, the light chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above embodiments, the heavy chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 18, and the light chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above embodiments, the heavy chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 19, and the light chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above embodiments, the heavy chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 24, and the light chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above embodiments, the heavy chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 25, and the light chain of the anti-TIGIT monoclonal antibody includes the amino acid sequence of SEQ ID NO: 20.In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody is a full-length antibody. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody is a full-length IgG antibody. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody is a full-length IgG1 antibody. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody is a full-length human IgG1 antibody. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody is a full-length humanized IgG1 antibody. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody retains one or more effector functions. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody retains all effector functions. In some embodiments of any of the above embodiments, one or more effector functions of the anti-TIGIT monoclonal antibody may be modified or removed. In some embodiments of any of the above embodiments, the anti-TIGIT monoclonal antibody is tiragolumab. Tiragolumab refers to the anti-TIGIT monoclonal antagonist antibody listed in WHO Drug Information (International Nonproprietary Names for Pharmaceutical Substances), Proposed INN: List 117, Vol. 31, No. 2, published June 9, 2017 (see page 343). In some embodiments, tiragolumab has CAS registry number 1918185-84-8. The anti-TIGIT monoclonal antibody may be an antibody fragment.

[0157] In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody comprises VH containing the amino acid sequence of SEQ ID NO: 16. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody comprises VH containing the amino acid sequence of SEQ ID NO: 16. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody comprises VL containing the amino acid sequence of SEQ ID NO: 17. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody comprises VH containing the amino acid sequence of SEQ ID NO: 16 and VL containing the amino acid sequence of SEQ ID NO: 17. In some embodiments of any of the above embodiments, the heavy chain of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 21. In some embodiments of any of the above embodiments, the heavy chain of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 22. In some embodiments of any of the above embodiments, the light chain of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 23. In some embodiments of any of the above embodiments, the heavy chain of the anti-PD-L1 monoclonal antibody contains the amino acid sequence of SEQ ID NO: 21, and the light chain of the anti-PD-L1 monoclonal antibody contains the amino acid sequence of SEQ ID NO: 23. In some embodiments of any of the above embodiments, the heavy chain of the anti-PD-L1 monoclonal antibody contains the amino acid sequence of SEQ ID NO: 22, and the light chain of the anti-PD-L1 monoclonal antibody contains the amino acid sequence of SEQ ID NO: 23. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody is a full-length antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is a full-length IgG antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is a full-length IgG1 antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is a full-length human IgG1 antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is a full-length humanized IgG1 antibody. In some embodiments of any of the above embodiments, the anti-PD-L1 monoclonal antibody retains one or more effector functions. In some embodiments of any of the above-described aspects, the anti-PD-L1 monoclonal antibody retains all effector functions.In some embodiments of any of the above aspects, one or more effector functions of the anti-PD-L1 monoclonal antibody may be modified or removed. The anti-PD-L1 monoclonal antibody may be an antibody fragment. In some embodiments, the anti-PD-L1 monoclonal antibody is atezolizumab. In some embodiments, the anti-PD-L1 monoclonal antibody is atezolizumab marketed as TECENTRIQ®. Atezolizumab is listed in WHO Drug Information (International Nonproprietary Names for Pharmaceutical Substances), Proposed INN: List 112, Vol. 28, No. 4, 2014 (see page 488). In some embodiments, atezolizumab has CAS registry number 1380723-44-3.

[0158] In another embodiment, the Disclosure provides a manufactured product comprising a formulation suitable for subcutaneous injection, comprising (a) about 1,000 mg of tiragolumab, (b) about 1,875 mg or about 2,000 mg of atezolizumab, (c) about 20 mM histidine acetate, (d) about 240 mM sucrose, (e) about 10 mM methionine, (f) about 0.06% (w / v) of polysorbate 20, and (g) about 2,000 U / mL of hyaluronidase, with a pH of about 5.8. In some embodiments, the product includes a formulation suitable for subcutaneous injection, comprising (a) about 1,000 mg of tiragolumab, (b) about 1,875 mg or about 2,000 mg of atezolizumab, (c) about 20 mM histidine acetate, (d) about 240 mM sucrose, (e) about 10 mM methionine, (f) about 0.06% (w / v) polysorbate 20, and (g) about 2,000 U / mL of hyaluronidase, with a pH of about 5.8.

[0159] In some embodiments, the product includes a formulation suitable for subcutaneous injection, comprising (a) about 1,000 mg of tiragolumab, (b) about 1,875 mg or about 2,000 mg of atezolizumab, (c) about 20 mM histidine acetate, (d) about 240 mM sucrose, (e) about 10 mM methionine, (f) about 0.06% (w / v) polysorbate 20, and (g) about 2,000 U / mL of hyaluronidase, with a pH of about 5.8.

[0160] In some embodiments, the manufactured product includes a formulation suitable for subcutaneous injection, comprising (a) about 1,000 mg of tiragolumab, (b) about 1,875 mg of atezolizumab, (c) about 20 mM histidine acetate, (d) about 240 mM sucrose, (e) about 10 mM methionine, (f) about 0.06% (w / v) of polysorbate 20, and (g) about 2,000 U / mL of hyaluronidase, with a pH of about 5.8.

[0161] In some embodiments, the manufactured product includes a formulation suitable for subcutaneous injection, comprising (a) about 1,000 mg of tiragolumab, (b) about 2,000 mg of atezolizumab, (c) about 20 mM histidine acetate, (d) about 240 mM sucrose, (e) about 10 mM methionine, (f) about 0.06% (w / v) of polysorbate 20, and (g) about 2,000 U / mL of hyaluronidase, with a pH of about 5.8.

[0162] In some embodiments, the product includes a formulation suitable for subcutaneous injection, comprising (a) 1,000 mg tiragolumab, (b) 1,875 mg or 2,000 mg atezolizumab, (c) 20 mM histidine acetate, (d) 240 mM sucrose, (e) 10 mM methionine, (f) 0.06% (w / v) polysorbate 20, and (g) 2,000 U / mL hyaluronidase, with a pH of 5.8.

[0163] In some embodiments, the product includes a formulation suitable for subcutaneous injection, comprising (a) 1,000 mg tiragolumab, (b) 1,875 mg atezolizumab, (c) 20 mM histidine acetate, (d) 240 mM sucrose, (e) 10 mM methionine, (f) 0.06% (w / v) polysorbate 20, and (g) 2,000 U / mL hyaluronidase, with a pH of 5.8.

[0164] In some embodiments, the product includes a formulation suitable for subcutaneous injection, comprising (a) 1,000 mg tiragolumab, (b) 2,000 mg atezolizumab, (c) 20 mM histidine acetate, (d) 240 mM sucrose, (e) 10 mM methionine, (f) 0.06% (w / v) polysorbate 20, and (g) 2,000 U / mL hyaluronidase, with a pH of 5.8.

[0165] In some embodiments of any of the above-described aspects, the product includes a subcutaneous administration device. In some embodiments, the subcutaneous administration device is selected from the group consisting of syringes, syringe pumps, injection devices, drip pumps, syringe pens, needleless devices, auto-injectors, and subcutaneous patch delivery systems. In some embodiments, the subcutaneous administration device is a syringe. In some embodiments, the subcutaneous administration device is a syringe pump. In some embodiments, the subcutaneous administration device is an injection device. In some embodiments, the subcutaneous administration device is an drip pump. In some embodiments, the subcutaneous administration device is a syringe pen. In some embodiments, the subcutaneous administration device is a needleless device. In some embodiments, the subcutaneous administration device is an auto-injector. In some embodiments, the subcutaneous administration device is a subcutaneous patch delivery system. In some embodiments, the subcutaneous administration device is a pre-filled syringe.

[0166] In some embodiments of any of the above-described aspects, the formulation contained in the product is the formulation of the Disclosure. In some embodiments of any of the above-described aspects, the product contains the formulation of the Disclosure.

[0167] Pharmaceutical preparations In another embodiment, the present disclosure provides a liquid pharmaceutical formulation comprising 160 mg / mL of tiragolumab and 2000 U / mL of hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.5. In some embodiments, the formulation comprises 160 mg / mL of tiragolumab and 2000 U / mL of hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.5. In some embodiments, the solution contains 160 mg / mL of tiragolumab and 2000 U / mL of rHuPH20 in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.5.

[0168] In another embodiment, the Disclosure provides a liquid pharmaceutical formulation comprising 40 mg / mL tiragolumab, 80 mg / mL atezolizumab, and 2000 U / mL hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.8. In some embodiments, the formulation comprises 40 mg / mL tiragolumab, 80 mg / mL atezolizumab, and 2000 U / mL hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.8.

[0169] In some embodiments, the formulation contains 40 mg / mL of tiragolumab, 80 mg / mL of atezolizumab, and 2000 U / mL of rHupH2O in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.8.

[0170] Exemplary Embodiments Specific embodiments of this disclosure are shown in the following numbered paragraphs. 1. A method for treating cancer, comprising subcutaneously administering an anti-TIGIT monoclonal antibody at a dose of approximately 1,000 mg to a subject requiring cancer treatment, wherein the anti-TIGIT monoclonal antibody is a full-length antibody comprising a heavy chain variable region including HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, HVR-H2 containing the amino acid sequence of SEQ ID NO: 2, and HVR-H3 containing the amino acid sequence of SEQ ID NO: 3, and a light chain variable region including HVR-L1 containing the amino acid sequence of SEQ ID NO: 4, HVR-L2 containing the amino acid sequence of SEQ ID NO: 5, and HVR-L3 containing the amino acid sequence of SEQ ID NO: 6. 2. Use of approximately 1,000 mg of anti-TIGIT monoclonal antibody in the manufacture of a drug for treating cancer in a subject requiring cancer treatment, wherein the drug is formulated for subcutaneous administration, and the anti-TIGIT monoclonal antibody is a full-length antibody comprising a heavy chain variable region containing HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, HVR-H2 containing the amino acid sequence of SEQ ID NO: 2, and HVR-H3 containing the amino acid sequence of SEQ ID NO: 3, and a light chain variable region containing HVR-L1 containing the amino acid sequence of SEQ ID NO: 4, HVR-L2 containing the amino acid sequence of SEQ ID NO: 5, and HVR-L3 containing the amino acid sequence of SEQ ID NO: 6. 3. An anti-TIGIT monoclonal antibody for use in the treatment of cancer in patients requiring cancer treatment, wherein the anti-TIGIT monoclonal antibody is a full-length antibody comprising a heavy chain variable region containing HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, HVR-H2 containing the amino acid sequence of SEQ ID NO: 2, and HVR-H3 containing the amino acid sequence of SEQ ID NO: 3, and a light chain variable region containing HVR-L1 containing the amino acid sequence of SEQ ID NO: 4, HVR-L2 containing the amino acid sequence of SEQ ID NO: 5, and HVR-L3 containing the amino acid sequence of SEQ ID NO: 6, and is administered subcutaneously at a dose of approximately 1,000 mg. 4. The anti-TIGIT monoclonal antibody is administered to the thigh or abdomen, according to the method described in Embodiment 1, the use described in Embodiment 2, or the anti-TIGIT monoclonal antibody described in Embodiment 3. 5. The anti-TIGIT monoclonal antibody is administered every three weeks (Q3W) according to the method described in Embodiment 1 or 4, the use described in Embodiment 2 or 4, or the anti-TIGIT monoclonal antibody described in Embodiment 3 or 4. 6. A method for treating cancer in a patient requiring cancer treatment, comprising subcutaneous administration of approximately 1,000 mg of anti-TIGIT monoclonal antibody and administration of approximately 1,875 mg to approximately 2,000 mg of anti-PD-L1 monoclonal antibody, wherein the anti-TIGIT monoclonal antibody comprises a heavy chain variable region including HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, HVR-H2 containing the amino acid sequence of SEQ ID NO: 2, and HVR-H3 containing the amino acid sequence of SEQ ID NO: 3, and HVR-L1 containing the amino acid sequence of SEQ ID NO: 4, and amino acids of SEQ ID NO: 5 A method comprising a full-length antibody containing a light chain variable region containing HVR-L2 containing the sequence and HVR-L3 containing the amino acid sequence of SEQ ID NO: 6, wherein the anti-PD-L1 monoclonal antibody is a full-length antibody containing a heavy chain variable region containing HVR-H1 containing the amino acid sequence of SEQ ID NO: 10, HVR-H2 containing the amino acid sequence of SEQ ID NO: 11, and HVR-H3 containing the amino acid sequence of SEQ ID NO: 12, and a light chain variable region containing HVR-L1 containing the amino acid sequence of SEQ ID NO: 13, HVR-L2 containing the amino acid sequence of SEQ ID NO: 14, and HVR-L3 containing the amino acid sequence of SEQ ID NO: 15. 7. Use of approximately 1,000 mg of anti-TIGIT monoclonal antibody and approximately 1,875 mg to approximately 2,000 mg of anti-PD-L1 monoclonal antibody in the manufacture of a drug for treating cancer in a subject requiring cancer treatment, wherein the drug is formulated for subcutaneous administration, and the anti-TIGIT monoclonal antibody comprises a heavy chain variable region including HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, HVR-H2 containing the amino acid sequence of SEQ ID NO: 2, and HVR-H3 containing the amino acid sequence of SEQ ID NO: 3, and HVR-L1 containing the amino acid sequence of SEQ ID NO: 4, and amino acid sequence of SEQ ID NO: 5 The full-length antibody contains a light chain variable region including HVR-L2 containing the amino acid sequence of SEQ ID NO: 6, and HVR-L3 containing the amino acid sequence of SEQ ID NO: 6. The anti-PD-L1 monoclonal antibody is a full-length antibody containing a heavy chain variable region including HVR-H1 containing the amino acid sequence of SEQ ID NO: 10, HVR-H2 containing the amino acid sequence of SEQ ID NO: 11, and HVR-H3 containing the amino acid sequence of SEQ ID NO: 12, and a light chain variable region including HVR-L1 containing the amino acid sequence of SEQ ID NO: 13, HVR-L2 containing the amino acid sequence of SEQ ID NO: 14, and HVR-L3 containing the amino acid sequence of SEQ ID NO: 15. 8. An anti-TIGIT monoclonal antibody and an anti-PD-L1 monoclonal antibody for use in the treatment of cancer in patients requiring cancer treatment, wherein the anti-TIGIT monoclonal antibody is a full-length antibody comprising a heavy chain variable region including HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, HVR-H2 containing the amino acid sequence of SEQ ID NO: 2, and HVR-H3 containing the amino acid sequence of SEQ ID NO: 3, and a light chain variable region including HVR-L1 containing the amino acid sequence of SEQ ID NO: 4, HVR-L2 containing the amino acid sequence of SEQ ID NO: 5, and HVR-L3 containing the amino acid sequence of SEQ ID NO: 6, and approximately 1,000 mg The anti-PD-L1 monoclonal antibody is administered subcutaneously at a dose of approximately 1,875 mg to 2,000 mg and is a full-length antibody containing a heavy chain variable region including HVR-H1 containing the amino acid sequence of SEQ ID NO: 10, HVR-H2 containing the amino acid sequence of SEQ ID NO: 11, and HVR-H3 containing the amino acid sequence of SEQ ID NO: 12, and a light chain variable region including HVR-L1 containing the amino acid sequence of SEQ ID NO: 13, HVR-L2 containing the amino acid sequence of SEQ ID NO: 14, and HVR-L3 containing the amino acid sequence of SEQ ID NO: 15. 9. The anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are administered simultaneously, as described in Embodiment 6, as described in Embodiment 7, or as described in Embodiment 8. 10. The anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are co-formulated according to the method of Embodiment 6 or 9, the use described in Embodiment 7 or 9, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody described in Embodiment 8 or 9. 11. The anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 24 hours prior to administration to the subject, as described in Embodiment 6 or 9, as described in Embodiment 7 or 9, or as described in Embodiment 8 or 9. 12. The anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed during administration to a subject, as described in Embodiment 11, used, or otherwise. 13. The anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are administered sequentially according to the method of Embodiment 6, the use described in Embodiment 7, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody described in Embodiment 8. 14. The anti-PD-L1 monoclonal antibody is administered intravenously by the method according to any one of Embodiments 6 and 9 to 13, the use described in any one of Embodiments 7 and 9 to 13, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody described in any one of Embodiments 8 to 13. 15. The anti-PD-L1 monoclonal antibody is administered subcutaneously by the method according to any one of Embodiments 6 and 9 to 13, the use described in any one of Embodiments 7 and 9 to 13, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody described in any one of Embodiments 8 to 13. 16. The anti-TIGIT monoclonal antibody is administered every three weeks (Q3W) according to the method of any one of Embodiments 6 and 9 to 15, the use described in any one of Embodiments 7 and 9 to 15, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody described in any one of Embodiments 8 to 15. 17. Cancers include lung cancer, non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, ureteral cancer, urethral cancer, colorectal cancer, colon cancer, rectal cancer, kidney cancer, sarcoma, ovarian cancer, breast cancer, cervical cancer, fallopian tube cancer, endometrial cancer, uterine cancer, pancreatic cancer, stomach cancer, bladder cancer, esophageal cancer, mesothelioma, melanoma, head and neck cancer, thyroid cancer, sarcoma, prostate cancer, penile cancer, glioblastoma, thymic cancer, esophageal cancer, nasopharyngeal cancer, mesothelioma, liver cancer, biliary tract cancer, HPV-positive cancer, leukemia, lymphoma, brain cancer, neuroendocrine cancer, myeloma, and mycosis fungus. A method according to any one of Embodiments 1, 4 to 6 and 9 to 16, selected from the group consisting of disease, Merkel cell carcinoma, hematological malignancies, mismatch repair deficiency (dMMR) cancer, and high microsatellite instability-H (MSI-H) cancer; a use according to any one of Embodiments 2, 4, 5, 7 and 9 to 16; an anti-TIGIT monoclonal antibody according to any one of Embodiments 3 to 5; or an anti-TIGIT monoclonal antibody and an anti-PD-L1 monoclonal antibody according to any one of Embodiments 8 to 16. 18. Cancers include bladder cancer, muscle-invasive bladder cancer, urothelial carcinoma, ureteral cancer, urethral cancer, ureteral urothelial carcinoma, urethral urothelial carcinoma, kidney cancer, renal pelvis cancer, renal cell carcinoma, clear cell kidney cancer, rectal cancer, colon cancer, colorectal cancer, sarcoma, osteosarcoma, leiomyosarcoma, pleomorphic sarcoma, myxofibrosarcoma, liposarcoma, chondrosarcoma, lung cancer, non-small cell lung cancer, fallopian tube cancer, peritoneal cancer, esophageal cancer, esophageal squamous cell carcinoma, mesothelioma, pleural mesothelioma, peritoneal mesothelioma, ovarian cancer, cervical cancer, cervical adenosquamous cell carcinoma, breast cancer, triple-negative breast cancer, H ER2-positive breast cancer, HER2-negative breast cancer, estrogen receptor-positive breast cancer, progesterone receptor-positive breast cancer, luminal type B breast cancer, lymphoma, T-cell lymphoma, B-cell lymphoma, nasal lymphoma, non-Hodgkin lymphoma, follicular lymphoma, penile cancer, prostate cancer, castration-resistant prostate cancer, endometrial cancer, uterine cancer, myeloma, multiple myeloma, head and neck cancer, prostate cancer, melanoma, cutaneous melanoma, Merkel cell carcinoma, pancreatic cancer, hepatocellular carcinoma, gastric cancer, gastroesophageal junction adenocarcinoma, glioblastoma, glioblastoma multiforme, bacteria Phagocytosis fungoides, HPV-positive cancer, HPV-associated cervical cancer, HPV-associated anal squamous cell carcinoma, HPV-associated penile squamous cell carcinoma, HPV-associated vulvar squamous cell carcinoma, vulvar cancer, vaginal cancer, anal cancer, oropharyngeal cancer, oropharyngeal squamous cell carcinoma, leukemia, acute myeloid leukemia, bone cancer, solitary osteoplasmacytoma, squamous cell carcinoma, cutaneous squamous cell carcinoma, thyroid cancer, metastatic colorectal cancer without microsatellite stability / mismatch repair deficiency (MSS / pMMR), cancer with mismatch repair deficiency (dMMR), high frequency microsatellite A method according to any one of Embodiments 1, 4 to 6 and 9 to 16, selected from the group consisting of Telite instability (MSI-H) cancer, nasal extranodal NK / T cell lymphoma, neuroendocrine cancer, biliary tract cancer, cholangiocarcinoma, and intrahepatic cholangiocarcinoma; a use according to any one of Embodiments 2, 4, 5, 7 and 9 to 16; an anti-TIGIT monoclonal antibody according to any one of Embodiments 3 to 5; or an anti-TIGIT monoclonal antibody and an anti-PD-L1 monoclonal antibody according to any one of Embodiments 8 to 16. 19. Cancer is selected from the group consisting of Merkel cell carcinoma, urothelial carcinoma, renal cell carcinoma, non-small cell lung cancer, breast cancer, triple-negative breast cancer, hepatocellular carcinoma, melanoma, Hodgkin lymphoma, head and neck cancer, colorectal cancer, gastric cancer, cervical cancer, mediastinal B-cell large cell lymphoma, cutaneous squamous cell carcinoma, basal cell carcinoma, bladder cancer, endometrial cancer, esophageal cancer, malignant pleural mesothelioma, cancers with high tumor mutation burden (TMB), mismatch repair deficiency (dMMR) cancer, and high microsatellite instability-H cancer, and is described in any one of Embodiments 1, 4 to 6 and 9 to 16, the use described in any one of Embodiments 2, 4, 5, 7 and 9 to 16, the anti-TIGIT monoclonal antibody described in any one of Embodiments 3 to 5, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody described in any one of Embodiments 8 to 16. 20. Cancers include lung cancer, non-small cell lung cancer, bronchogenic lung cancer, breast cancer, triple-negative breast cancer, estrogen receptor-positive breast cancer, HER2-positive breast cancer, metastatic lobular breast cancer, ductal carcinoma, cervical cancer, fallopian tube cancer, serous adenocarcinoma of the fallopian tube, ovarian cancer, ovarian endometrioid tumor, serous adenocarcinoma of the ovary, mucinous carcinoma of the ovary, uterine cancer, endometrial cancer, skin cancer, melanoma, cutaneous melanoma, Merkel cell carcinoma, head and neck cancer, squamous cell carcinoma of the head and neck, hematological malignancies, leukemia, myeloid leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, myelomonocytic leukemia, thyroid cancer, and thyroid cancer. Cancer, thymic carcinoma, neuroendocrine carcinoma, chromaffin cell tumor, glioma, glioblastoma multiforme, paraganglioma, lymphoma, B-cell lymphoma, Hodgkin lymphoma, B-cell non-Hodgkin lymphoma, non-Hodgkin lymphoma, cutaneous T-cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, marginal lymphoma, pancreatic cancer, pancreatic ductal adenocarcinoma, rectal cancer, colon cancer, colorectal cancer, urinary tract cancer, urogenital cancer, mesothelioma, pleural mesothelioma, peritoneal mesothelioma, sarcoma, chondrosarcoma, clear cell sarcoma, liposarcoma, myxoid / round cell liposarcoma, synovial sarcoma, hydatidiform soft part sarcoma, gliosarcoma, uterine cancer Sarcoma, kidney cancer, non-clear cell kidney cancer, renal cell carcinoma, bladder cancer, urothelial carcinoma, muscle-invasive bladder cancer, non-muscle-invasive bladder cancer, HER2-positive bladder cancer, gallbladder cancer, stomach cancer, esophageal cancer, esophageal squamous cell carcinoma, gastrointestinal cancer, gastroesophageal cancer, gastroesophageal junction cancer, HER2-positive stomach cancer, primary peritoneal cancer, cutaneous squamous cell carcinoma, prostate cancer, prostatic adenocarcinoma, castration-resistant prostate cancer, urogenital cancer, ureteral urothelial carcinoma, renal pelvis urothelial carcinoma, urethral urothelial carcinoma, appendiceal cancer, penile cancer, anal canal cancer, hepatocellular carcinoma, hepatobiliary tract cancer, unresectable liver and intrahepatic bile duct cancer, biliary tract The method according to any one of Embodiments 1, 4 to 6 and 9 to 16, selected from the group consisting of bile duct cancer, intrahepatic bile duct cancer, extrahepatic bile duct cancer, HPV-related cancer, HPV-related anal squamous cell carcinoma, HPV-related cervical squamous cell carcinoma, HPV-related penile squamous cell carcinoma, HPV-related vulvar squamous cell carcinoma, nasopharyngeal cancer, nasopharyngeal cancer, pharyngeal squamous cell carcinoma, hypopharyngeal squamous cell carcinoma, oral squamous cell carcinoma, and mycosis fungoides; the use described in any one of Embodiments 2, 4, 5, 7 and 9 to 16; the anti-TIGIT monoclonal antibody described in any one of Embodiments 3 to 5;Alternatively, the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody described in any one of embodiments 8 to 16. 21. Cancer is selected from the group consisting of urothelial carcinoma, non-small cell lung cancer (NSCLC), breast cancer, triple-negative breast cancer, hepatocellular carcinoma, and melanoma, and is the method according to any one of Embodiments 1, 4 to 6 and 9 to 16, the use according to any one of Embodiments 2, 4, 5, 7 and 9 to 16, the anti-TIGIT monoclonal antibody according to any one of Embodiments 3 to 5, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of Embodiments 8 to 16. 22. Cancer is selected from the group consisting of multiple myeloma, cervical cancer, esophageal cancer, esophageal squamous cell carcinoma, lung cancer, non-small cell lung cancer, glioblastoma, endometrial cancer, ovarian cancer, squamous cell carcinoma, and head and neck cancer, and is the method according to any one of Embodiments 1, 4 to 6 and 9 to 16, the use according to any one of Embodiments 2, 4, 5, 7 and 9 to 16, the anti-TIGIT monoclonal antibody according to any one of Embodiments 3 to 5, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of Embodiments 8 to 16. 23. Cancer is selected from the group consisting of cervical cancer, head and neck squamous cell carcinoma, head and neck cancer, non-small cell lung cancer, non-squamous non-small cell lung cancer, esophageal squamous cell carcinoma, esophageal cancer, breast cancer, triple-negative breast cancer, gastric cancer, gastroesophageal junction adenocarcinoma, multiple myeloma, non-Hodgkin lymphoma, B-cell lymphoma, liver cancer, bladder cancer, urothelial carcinoma, pancreatic cancer, and pancreatic adenocarcinoma, and is the method according to any one of Embodiments 1, 4 to 6 and 9 to 16, the use according to any one of Embodiments 2, 4, 5, 7 and 9 to 16, the anti-TIGIT monoclonal antibody according to any one of Embodiments 3 to 5, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of Embodiments 8 to 16. 24. Cancer is a solid tumor, the method according to any one of Embodiments 1, 4 to 6 and 9 to 16, the use according to any one of Embodiments 2, 4, 5, 7 and 9 to 16, the anti-TIGIT monoclonal antibody according to any one of Embodiments 3 to 5, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of Embodiments 8 to 16. 25. The cancer is a blood cancer, the method according to any one of Embodiments 1, 4 to 6 and 9 to 16, the use according to any one of Embodiments 2, 4, 5, 7 and 9 to 16, the anti-TIGIT monoclonal antibody according to any one of Embodiments 3 to 5, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of Embodiments 8 to 16. 26. The heavy chain variable region of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 16, as described in any one of Embodiments 6 and 9 to 25, as described in any one of Embodiments 7 and 9 to 25, or as described in any one of Embodiments 8 to 25, the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody. 27. The light chain variable region of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 17, as described in any one of Embodiments 6 and 9 to 26, as described in any one of Embodiments 7 and 9 to 26, or as described in any one of Embodiments 8 to 26, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody. 28. The method according to any one of Embodiments 6 and 9 to 27, the use described in any one of Embodiments 7 and 9 to 27, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody described in any one of Embodiments 8 to 27, wherein the heavy chain variable region of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 16, and the light chain variable region of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 17. 29. The anti-PD-L1 monoclonal antibody is an IgG antibody, as described in any one of Embodiments 6 and 9 to 28, as described in any one of Embodiments 7 and 9 to 28, or as described in any one of Embodiments 8 to 28, the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody. 30. The method, use, or anti-TIGIT monoclonal antibody and anti-PD-L1 antibody as described in Embodiment 29, wherein the anti-PD-L1 monoclonal antibody is an IgG1 antibody or an IgG4 antibody. 31. The method according to any one of Embodiments 6 and 9 to 30, the use described in any one of Embodiments 7 and 9 to 30, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody described in any one of Embodiments 8 to 30, wherein the anti-PD-L1 monoclonal antibody or anti-TIGIT monoclonal antibody is a human antibody. 32. The method according to any one of Embodiments 6 and 9 to 30, the use described in any one of Embodiments 7 and 9 to 30, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody described in any one of Embodiments 8 to 30, wherein the anti-PD-L1 monoclonal antibody or anti-TIGIT monoclonal antibody is a humanized antibody. 33. The anti-PD-L1 monoclonal antibody is selected from the group consisting of atezolizumab (MPDL3280A), durvalumab (MEDI4736), avelumab, and MDX-1105, as described in any one of Embodiments 6 and 9 to 30, as described in any one of Embodiments 7 and 9 to 30, or as the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody described in any one of Embodiments 8 to 30. 34. The heavy chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 7 or SEQ ID NO: 8, as described in any one of Embodiments 1, 4 to 6 and 9 to 33, as described in any one of Embodiments 2, 4, 5, 7 and 9 to 33, as described in any one of Embodiments 3 to 5 and 17 to 25, or as described in any one of Embodiments 8 to 33, the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody. 35. The light chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 9, as described in any one of Embodiments 1, 4 to 6 and 9 to 34, as described in any one of Embodiments 2, 4, 5, 7 and 9 to 34, as described in any one of Embodiments 3 to 5, 17 to 25 and 34, or as described in any one of Embodiments 8 to 34, the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody. 36. The method according to any one of Embodiments 1, 4 to 6 and 9 to 35, the use according to any one of Embodiments 2, 4, 5, 7 and 9 to 35, the anti-TIGIT monoclonal antibody according to any one of Embodiments 3 to 5, 17 to 25 and 34 to 35, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of Embodiments 8 to 35. 37. The heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24, as described in any one of Embodiments 1, 4 to 6 and 9 to 36, as described in any one of Embodiments 2, 4, 5, 7 and 9 to 36, as described in any one of Embodiments 3 to 5, 17 to 25 and 34 to 36, or as described in any one of Embodiments 8 to 36, the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody. 38. The heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 19 or SEQ ID NO: 25, as described in any one of Embodiments 1, 4 to 6 and 9 to 37, as described in any one of Embodiments 2, 4, 5, 7 and 9 to 37, as described in any one of Embodiments 3 to 5, 17 to 25 and 34 to 37, or as described in any one of Embodiments 8 to 37, the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody. 39. The light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20, as described in any one of Embodiments 1, 4 to 6 and 9 to 38, as described in any one of Embodiments 2, 4, 5, 7 and 9 to 38, as described in any one of Embodiments 3 to 5, 17 to 25 and 34 to 38, or as described in any one of Embodiments 8 to 38, the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody. 40. The method according to any one of Embodiments 1, 4 to 6 and 9 to 39, the use according to any one of Embodiments 2, 4, 5, 7 and 9 to 39, the anti-TIGIT monoclonal antibody according to any one of Embodiments 3 to 5, 17 to 25 and 34 to 39, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of Embodiments 8 to 39. 41. The method according to any one of Embodiments 1, 4 to 6 and 9 to 39, the use according to any one of Embodiments 2, 4, 5, 7 and 9 to 39, the anti-TIGIT monoclonal antibody according to any one of Embodiments 3 to 5, 17 to 25 and 34 to 39, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of Embodiments 8 to 39. 42. The anti-TIGIT monoclonal antibody is an IgG antibody, the method according to any one of Embodiments 1, 4 to 6 and 9 to 41, the use according to any one of Embodiments 2, 4, 5, 7 and 9 to 41, the anti-TIGIT monoclonal antibody according to any one of Embodiments 3 to 5, 17 to 25 and 34 to 41, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of Embodiments 8 to 41. 43. The method, use, anti-TIGIT monoclonal antibody, or anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to Embodiment 42, wherein the anti-TIGIT monoclonal antibody is an IgG1 antibody or an IgG4 antibody. 44. The anti-TIGIT monoclonal antibody is a human antibody, the method according to any one of Embodiments 1, 4 to 6 and 9 to 43, the use according to any one of Embodiments 2, 4, 5, 7 and 9 to 43, the anti-TIGIT monoclonal antibody according to any one of Embodiments 3 to 5, 17 to 25 and 34 to 43, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of Embodiments 8 to 43. 45. The anti-TIGIT monoclonal antibody is a humanized antibody, the method according to any one of Embodiments 1, 4 to 6 and 9 to 43, the use according to any one of Embodiments 2, 4, 5, 7 and 9 to 43, the anti-TIGIT monoclonal antibody according to any one of Embodiments 3 to 5, 17 to 25 and 34 to 43, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of Embodiments 8 to 43. 46. ​​The anti-TIGIT monoclonal antibody is the method according to any one of Embodiments 1, 4 to 6 and 9 to 43, the use according to any one of Embodiments 2, 4, 5, 7 and 9 to 43, the anti-TIGIT monoclonal antibody according to any one of Embodiments 3 to 5, 17 to 25 and 34 to 43, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of Embodiments 8 to 43, which inhibit or block the interaction between CD226 and TIGIT. 47. The anti-TIGIT monoclonal antibody is tiragolumab, the method according to any one of Embodiments 1, 4 to 6 and 9 to 43, the use according to any one of Embodiments 2, 4, 5, 7 and 9 to 43, the anti-TIGIT monoclonal antibody according to any one of Embodiments 3 to 5, 17 to 25 and 34 to 43, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of Embodiments 8 to 43. 48. The anti-TIGIT monoclonal antibody is present in a liquid pharmaceutical composition containing 160 mg / mL tiragolumab and 2000 U / mL hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.5, as described in any one of Embodiments 1, 4 to 6 and 9 to 47, as described in any one of Embodiments 2, 4, 5, 7 and 9 to 47, as the anti-TIGIT monoclonal antibody described in any one of Embodiments 3 to 5, 17 to 25 and 34 to 47, or as the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody described in any one of Embodiments 8 to 47. 49. The anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody are present in a liquid pharmaceutical formulation containing 40 mg / ml tiragolumab, 80 mg / ml atezolizumab, and 2000 U / ml hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.8, according to the method of any one of Embodiments 6 and 9 to 47, the use described in any one of Embodiments 7 and 9 to 47, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody described in any one of Embodiments 8 to 47. A manufactured product containing a formulation with 50.1,000 mg of tiragolumab. 51. The preparation is the manufactured product according to Embodiment 50, further comprising 1,875 mg or 2,000 mg of atezolizumab. 52. The preparation is the manufactured product according to Embodiment 50, further comprising 1,875 mg of atezolizumab. 53. The preparation is the manufactured product according to Embodiment 50, further comprising 2,000 mg of atezolizumab. 54. The preparation is a manufactured product according to any one of embodiments 50 to 53, further comprising hyaluronidase. A manufactured product containing a formulation comprising 55.1,000 mg of tiragolumab and 1,875 mg or 2,000 mg of atezolizumab. 56. The formulation is the manufactured product according to Embodiment 55, containing 1,875 mg of atezolizumab. 57. The formulation is the manufactured product described in Embodiment 55, containing 2,000 mg of atezolizumab. 58. The preparation is a product according to any one of embodiments 55 to 57, further comprising hyaluronidase. 59. The manufactured product according to Embodiment 54 or 58, wherein the concentration of hyaluronidase is 2000 U / mL. 60. The product according to any one of embodiments 54 and 58 to 59, wherein the hyaluronidase is recombinant human hyaluronidase. 61. The manufactured product according to Embodiment 60, wherein the recombinant hyaluronidase is a human soluble pH20 hyaluronidase glycoprotein such as rHuPH20. 62. The product according to any one of embodiments 50 to 61, wherein the product is a vial. 63. The manufactured product according to Embodiment 62, wherein the vial is a single-dose vial. 64. The product according to embodiment 62 or 63, wherein the vial is capped with a chlorobutyl elastomer stopper. 65. The product according to any one of embodiments 50 to 61, wherein the product is a pre-filled syringe. 66. The manufactured product according to any one of embodiments 50 to 61, wherein the manufactured product is a syringe pump. 67. The manufactured product is a subcutaneous administration device, as described in any one of embodiments 50 to 61. 68. The manufactured product according to Embodiment 67, wherein the subcutaneous administration device is selected from the group consisting of syringes, syringe pumps, injection devices, drip pumps, syringe pens, needleless devices, auto-injectors, and subcutaneous patch delivery systems. 69. A manufactured product comprising a subcutaneous administration device, wherein the subcutaneous administration device contains a fixed dose of 1,000 mg of tiragolumab and delivers it to a patient. 70. The manufactured product according to Embodiment 69, wherein the subcutaneous administration device further contains a fixed dose of 1,875 mg or 2,000 mg of atezolizumab and delivers it to a patient. 71. The manufactured product according to Embodiment 70, wherein the subcutaneous administration device further contains a fixed dose of 1,875 mg of atezolizumab and delivers it to a patient. 72. The manufactured product according to Embodiment 70, wherein the subcutaneous administration device further contains a fixed dose of 2,000 mg of atezolizumab and delivers it to the patient. 73. A product according to any one of embodiments 69 to 72, wherein the subcutaneous administration device further contains hyaluronidase and delivers it to a patient. 74. The hyaluronidase is a human soluble pH20 hyaluronidase glycoprotein such as rHuPH20, as described in Embodiment 73. 75. A manufactured product according to any one of embodiments 69 to 74, wherein the subcutaneous administration device is selected from the group consisting of syringes, syringe pumps, injection devices, infusion pumps, syringe pens, needleless devices, auto-injectors, and subcutaneous patch delivery systems. 76. A manufactured product according to any one of embodiments 69 to 75, wherein the subcutaneous administration device is a syringe. 77. The manufactured product according to any one of embodiments 69 to 75, wherein the subcutaneous administration device is a syringe pump. 78. The manufactured product according to any one of Embodiments 50 to 77, comprising approximately 3 mL to approximately 60 mL of anti-TIGIT full-length monoclonal antibody and one or more of hyaluronidase, histidine buffer, sucrose, and polysorbate 20. 79. The manufactured product according to Embodiment 78, comprising approximately 10 mL of tiragolumab and one or more of hyaluronidase, histidine buffer, sucrose, and polysorbate 20. 80. The manufactured product according to Embodiment 78, comprising approximately 7 mL of tiragolumab and one or more of hyaluronidase, histidine buffer, sucrose, and polysorbate 20. 81. The manufactured product according to Embodiment 78, comprising approximately 6.5 mL of tiragolumab and one or more of hyaluronidase, histidine buffer, sucrose, and polysorbate 20. 82. The manufactured product according to Embodiment 78, comprising approximately 21 mL of tiragolumab and one or more of hyaluronidase, histidine buffer, sucrose, and polysorbate 20. [Examples]

[0171] Example 1. An open-label, multicenter dose-finding study of tiragolumab and atezolizumab. Two to three single-arm, open-label, multicenter dose-finding studies have been initiated and are ongoing, comparing the dose of subcutaneous (SC) administration of the anti-TIGIT monoclonal antibody tiragolumab with the dose of subcutaneous (IV) administration of the anti-PD-L1 monoclonal antibody atezolizumab to the dose of sequential intravenous (IV) administration of tiragolumab following atezolizumab. These studies analyze the pharmacokinetics (PK) of serum tiragolumab and atezolizumab (i.e., C1 (before Cycle 2 administration)). trough Based on the above, it is being performed on patients with locally advanced or metastatic solid tumors.

[0172] This study consists of the following three cohorts. • Cohort 1: Cycle 1: On day 1 of Cycle 1 (21 days), subjects received either (1) 880 mg tiragolumab SC co-mixed with 2000 mg atezolizumab SC in the abdomen, or (2) 880 mg tiragolumab SC co-mixed with 1875 mg atezolizumab SC in the thigh. Cycle 2 and beyond: From Cycle 2 onward, subjects received 1200 mg atezolizumab IV followed by 600 mg tiragolumab IV every three weeks (Q3W) (on day 1 of each cycle) until disease progression, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent was observed. • Cohort 2: Cycles 1-3: Participants receive 1,000 mg of tiragolumab SC co-mixed with 1,875 mg of atezolizumab SC in the thigh for 3 cycles (21 days each) at Q3W (3 weeks). Cycle 4 onwards: From cycle 4 onwards, participants receive 1,200 mg of atezolizumab IV followed by 600 mg of tiragolumab IV at Q3W (day 1 of each cycle) until disease progression, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent is observed. • Cohort 3: Cycles 1-3: Participants receive 1,000 mg tiragolumab SC co-mixed with 1,875 mg atezolizumab SC intraabdominally for 3 cycles (21 days each) at Q3W on day 1 of each cycle. Cycle 4 onwards: From cycle 4 onwards, participants receive 1,200 mg atezolizumab IV followed by 600 mg tiragolumab IV at Q3W (day 1 of each cycle) until disease progression, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent is observed.

[0173] Cohort 1 enrolled 30 eligible subjects (15 for abdominal injection (Cohort 1A) and 15 for thigh injection (Cohort 1B)). Cohorts 2 and 3 enrolled approximately 25-30 eligible subjects each, achieving at least 15 evaluable subjects in each cohort, for a total of approximately 74-100 eligible subjects. Cohort 3 may not be initiated or may enroll fewer subjects if sufficient data from Cohort 2 is deemed available. Based on the known PK profiles of tiragolumab IV and atezolizumab IV, the sample size allows for the estimation of PK parameters that enable Phase III dose selection.

[0174] Parameter estimates for the pharmacokinetic model were obtained after a single subcutaneous dose of 880 mg of tiragolumab was administered to 15 subjects in Cohort 1A, followed by an intravenous administration of 600 mg of tiragolumab. See Table 3. Pharmacokinetic model fits over time (days) were generated using data from two representative subjects from Cohort 1A and two representative subjects from Cohort 1B. See Figures 2A and 2B, respectively. [Table 3] TIFF2026513259000007.tif36170

[0175] Twenty hundred simulated clinical trials based on population pharmacokinetic models were conducted using patient characteristics from 326 subjects. Table 4 below shows a summary statistical table of simulated serum tiragolumab concentrations after administration of the specified regimens and number of doses to the simulated subjects.

[0176] As shown in Table 4, statistical analysis of the predicted pharmacokinetic profile indicates that subcutaneous administration of 1000 mg of tiragolumab Q3W is not inferior to intravenous administration of 600 mg of tiragolumab Q3W, regardless of whether the subcutaneous dose is administered to the abdomen or thigh, as shown by the AUC and Cmin values ​​for predicted cycle 1. Therefore, the 1000 mg subcutaneous dose is as effective as 600 mg of tiragolumab Q3W IV. Consequently, subcutaneous administration of 1000 mg of tiragolumab was selected as the dose for cohorts 2 and 3. [Table 4] TIFF2026513259000009.tif222170

[0177] Subjects who discontinued the study treatment early for reasons other than toxicity (defined as discontinuation before completion of 2 cycles in Cohort 1, or before completion of 4 cycles in Cohorts 2 and 3) may be replaced if they are deemed unreviewable.

[0178] All subjects are required to report any symptoms and adverse events as soon as possible, especially within the first 72 hours after the initial injection. The first two patients in each of the thigh and abdominal injection groups in Cohort 1 (subjects in the thigh and abdominal injection groups may be enrolled simultaneously), and the first two subjects in each of Cohorts 2 and 3 (subjects in Cohorts 2 and 3 may be enrolled simultaneously), will be observed for one week before administration to subsequent subjects. In the thigh and abdominal groups of Cohorts 2 and 3, subsequent subjects will not be enrolled in stages. Cohort reviews of all safety data will begin 7 days after the last subject in each cohort has received its second cycle of administration.

[0179] After the start of the study treatment, all adverse events will be reported up to 30 days after the last dose of the study treatment or until the start of new systemic anticancer therapy, whichever comes first. Serious adverse events will continue to be reported up to 90 days after the last dose of the study treatment or until the start of new systemic anticancer therapy, whichever comes first. In addition, adverse events of particular interest will continue to be reported up to 90 days after the last dose of the study treatment, regardless of the subsequent initiation of anticancer therapy. After this period, all deaths or serious adverse events thought to be related to prior treatment with the study drug(s) will be reported. Each adverse event will be followed until the event resolves to baseline grade or better, the event is assessed as stable, the subject is removed from follow-up, or the subject withdraws consent. All efforts should be made to track all serious adverse events thought to be related to the study treatment or protocol-related procedures until the final results can be reported.

[0180] Tumor assessments were performed every 6 weeks (Q6W) (±7 days) for the first 48 weeks, and thereafter every 9 weeks (Q9W) (±7 days) until radiological disease progression (PD) or loss of clinical benefit. Participants were followed for overall survival (OS) until death, loss of follow-up, withdrawal from the study, or termination of the study, whichever occurred first.

[0181] Figure 1 shows an overview of the experimental design.

[0182] basis This study will determine the dosage and administration site of tiragolumab and atezolizumab via SC co-administration compared to their respective IV routes of administration, and will evaluate safety, tolerability, and pharmacokinetics (PK). Previous studies have only examined IV administration for both tiragolumab and atezolizumab in combination. Bioavailability, safety, immunogenicity, and preliminary efficacy data for tiragolumab and atezolizumab in combination after SC administration will facilitate further development of the SC route of administration. In addition, the safety, PK, and immunogenicity of rHuPH20 will also be evaluated. Co-composition with 2000 U / mL of rHuPH20 will be generated from the atezolizumab SC and tiragolumab SC pharmaceuticals. Objectives and evaluation items

[0183] This study was designed to evaluate the pharmacokinetics (PK), safety, tolerability, and exploratory efficacy of various doses of tiragolumab and atezolizumab administered as a single SC injection (i.e., SC comix of tiragolumab and atezolizumab with rHuPH20), as well as various doses of tiragolumab and atezolizumab IV administered sequentially, in patients with locally advanced or metastatic solid tumors. The objectives and corresponding endpoints are described in Table 5 below. [Table 5] TIFF2026513259000011.tif183170

[0184] Participants in Cohort 1 underwent tumor assessments at baseline and at Q6W (±7 days) over 48 weeks, starting from day 1 of cycle 1. After completion of the tumor assessment at 48 weeks, tumor assessments were performed every 9 weeks (±7 days) in accordance with RECIST v1.1 until the first occurrence of radiological disease progression, withdrawal of consent, death, or termination of the study. Participants continuing treatment after disease progression according to RECIST v1.1 underwent tumor assessments at Q6W (±2 weeks) after the first recording of progression, or more frequently at any point in the study where clinical indications exist, until treatment was discontinued. Scans may be performed at any time if disease progression or loss of clinical benefit is suspected.

[0185] The response was evaluated using the imaging methods described above (e.g., CT scans and MRI) with RECIST v1.1. Overall tumor response assessments at all time points were performed based on RECIST v1.1. Results were reviewed before administration in the next cycle. Investigational treatment with tiragolumab and atezolizumab will be continued as long as there is no unacceptable toxicity or symptomatic exacerbation due to disease progression and the subject experiences clinical benefit, after a comprehensive evaluation of radiographic imaging data, biopsy results, and clinical status. Subjects meeting the criteria for disease progression according to RECIST v1.1 will be permitted to continue investigational treatment if they meet all criteria and provide written consent.

[0186] Efficacy evaluation, biomarkers, and biological samples Objective response is assessed according to RECIST v1.1 and determined by repeated assessments at least four weeks after the initial recording of complete response (CR) and partial response (PR). The clinical tests to be performed include the following: 1. Serological tests: HIV serological tests, HBV serological tests (e.g., HBsAg, HBsAb, and total HBcAb); HBV DNA of subjects who are negative for HBsAg and HBsAb tests and positive for total HBcAb; HCV serological tests (e.g., HCV antibody and (if HCV antibody test is positive) HCV RNA); EBV serological tests (e.g., EBV viral capsid antigen (VCA) IgM; EBV VCA IgG or EBV nuclear antigen (EBNA) IgG; and EBV PCR); 2. Hematological tests: White blood cell (WBC) count and differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes), red blood cell (RBC) count, hemoglobin, hematocrit, platelet count, and differential count; 3. Chemical panel (serum or plasma): bicarbonate or total carbon dioxide (if considered standard treatment in the region), sodium, magnesium, potassium, calcium, chloride, glucose, blood urea nitrogen (BUN) or urea, creatinine, total protein, albumin, phosphate, total bilirubin, ALP, ALT, AST, and lactate dehydrogenase (LDH); 4. Serum C-reactive protein (CRP) 5. Urinalysis, including urine test strip tests (pH, specific gravity, glucose, protein, ketones, blood); 6. Pregnancy Testing: All women of childbearing age will undergo a serum pregnancy test during screening 14 days prior to the start of the study drug. During the study, a urine pregnancy test will be performed within 96 hours of the first dose of each cycle and after discontinuation of the study treatment. 7. Coagulation (INR and aPTT) or prothrombin time (PTT); and 8. Thyroid-stimulating hormone (TSH), free T3 (or total T3 if free T3 is not performed at the facility), and free T4;

[0187] The following samples for clinical tests will be sent for analysis. 1. Serum and plasma samples for PK analysis (tiragolumab and atezolizumab using validated assays). PK / ADA samples may be interchangeably used for PK / ADA-related assessments. 2. Serum and plasma samples for ADA analysis using validated assays (tiragolumab, atezolizumab, and rHuPH20); 3. Plasma samples for rHuPH20 concentration using validated assays; 4. Blood, plasma, serum, and peripheral blood mononuclear cells (PBMCs) for exploratory biomarker studies. 5. For exploratory biomarkers including but not limited to PD-L1 and TIGIT, preserved tissue samples obtained at baseline (if available). a. Ten to fifteen slides containing representative FFPE tumor specimens in paraffin blocks or newly cut, unstained serial sections from FFPE tumor specimens shall be submitted along with the relevant pathology report prior to trial registration. b. Tumor tissue is of good quality based on total tumor content and viable tumor content. The most recent biopsy with the highest tumor content and smallest necrotic area is preferred. Samples obtained by excision, core needle biopsy (at least three cores embedded in a single paraffin block), or by excision biopsy, incision biopsy, punch biopsy, forceps biopsy, or EBUS-TBNA are acceptable. Fine needle aspiration (defined as a sample that does not retain tissue structure and produces a cell suspension and / or smear), brushing, cell pellets from pleural fluid, and lavage fluid samples are not acceptable. Tumor tissue from decalcified bone metastases is not acceptable. c. If preserved tumor tissue is deemed unavailable or unsuitable for the necessary examinations, a fresh tumor biopsy prior to treatment may be required.

[0188] Exploratory biomarker studies may include, but are not limited to, analysis of genes or gene signatures related to tumor immunobiology (e.g., PD-L1 and TIGIT), lymphocyte subpopulations, T cell receptor repertoire, or cytokines associated with T cell activation. Studies may include DNA, cell-free DNA, or RNA extraction; analysis of mutations, single nucleotide polymorphisms, and other genomic variants; and genomic profiling using next-generation sequencing (NGS) of comprehensive gene panels. Somatic variants can be identified by comparing DNA extracted from blood with DNA extracted from tissue to distinguish germline variants from somatic variants. NGS methods may include whole-genome sequencing (WGS) or whole-exome sequencing (WES) of blood samples, but are optional and performed only at participating institutions.

[0189] The safety assessments conducted in this study included monitoring and recording of adverse events (e.g., serious adverse events and adverse events of particular interest), conducting safety clinical assessments, measuring vital signs (e.g., pulse rate, respiratory rate, blood pressure, and body temperature), and performing other tests deemed important for the safety assessment of the study.

[0190] PK analysis In the PK analysis for subjects in Cohort 1, subjects were grouped by treatment, and key parameters (e.g., area under the concentration-time curve [AUC], time to maximum concentration [t]) were analyzed. max ], maximum concentration [C max ], half-life, C trough Sufficient data was provided to enable estimation of these parameters. Estimates of these parameters were compiled and summarized (mean, standard deviation, coefficient of variation, median, minimum, and maximum). See Table 4. Inter-subject variability and drug accumulation were evaluated. Additional PK analysis will be performed as needed.

[0191] Subcutaneous administration Comixtures of atezolizumab SC and tilagorumab SC were prepared from atezolizumab SC and tilagorumab SC pharmaceuticals, each containing rHuPH20 at a concentration of 2000 U / mL. The pharmaceuticals were administered subcutaneously to the anterior thigh region or lower abdomen. Subjects in Cohort 1 received one dose of the atezolizumab SC and tilagorumab SC comix via the SC route. Subjects in Cohorts 2 and 3 received three doses of the atezolizumab SC and tilagorumab SC comix via the SC route. The atezolizumab SC and tilagorumab SC comixes were administered according to the instructions outlined in Table 6. [Table 6]

[0192] SC injections were administered at a rate of 1.0 mL / min to 2.0 mL / min using either a B. Braun Perfusor® Space Infusion Pump or a Smiths Medical Medfusion Syringe Pump. The SC dose was administered using a disposable Becton-Dickenson plastic syringe and a KORU HigH-Flo 24G SC injection set with one or more syringe pumps.

[0193] If applicable, the injection site should be selected alternately between the left and right thighs. The new injection should be administered at least 2.5 cm from the previous site, and never inject into areas of redness, injury, tenderness, or hardness of the skin. When administering to the abdomen, the injection should be administered into one of the two lower quadrants around the navel, and not above the navel. In all cases (abdomen or thigh), the start and stop times of the SC injection should be recorded.

[0194] Premedication is not permitted for the initial dose of the atezolizumab SC and tiragolumab SC combination. Premedication may be administered for cycles >2 at the discretion of the treating physician. If a serious adverse reaction is observed at the injection site, the injection site will be digitally photographed after the SC injection. After the initial dose, the patient will remain in the ward for 8 hours. Thereafter, the patient will be revisited on a designated day for safety evaluation.

[0195] The vital signs of the target individual (e.g., pulse rate, respiratory rate, blood pressure, and body temperature) should be measured 60 minutes before and within 30 (±10) minutes after injection, and where clinically indicated.

[0196] Intravenous administration Administration of atezolizumab and tilagorumab IV, initiated in cycle 2 of Cohort 1, was conducted under supervision with trained personnel to manage potentially serious reactions and immediate access to appropriate equipment and medications. Dose changes of atezolizumab or tilagorumab were not permitted.

[0197] Atezolizumab IV infusion was administered according to the instructions outlined in Table 7. Following the administration of atezolizumab and the observation period (see Table 7), subjects received 600 mg of tiragolumab administered by IV infusion on day 1 of each 21-day cycle. [Table 7]

[0198] Tiragolumab was administered according to the instructions outlined in Table 8. [Table 8]

[0199] Unless atezolizumab or tilagolmab has been permanently discontinued, the following rules apply: The treatment cycle begins with the administration of atezolizumab and tiragolumab on day 1 of each 21-day cycle. If either study drug is delayed due to drug-related toxicity, it is recommended that the other study drug also be delayed, as the safety profiles of atezolizumab and tiragolumab are similar. However, if deemed appropriate, the cycle may begin with the administration of the other study drug. If administration of one investigational drug is delayed due to drug-related toxicity, while the other investigational drug is administered as planned, it is recommended that the delayed investigational drug be administered in the next scheduled infusion (i.e., the next scheduled 21-day cycle).

Claims

1. A method for treating cancer, comprising subcutaneously administering an anti-TIGIT monoclonal antibody at a dose of approximately 1,000 mg to a subject requiring cancer treatment, wherein the anti-TIGIT monoclonal antibody is a full-length antibody comprising a heavy chain variable region including HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, HVR-H2 containing the amino acid sequence of SEQ ID NO: 2, and HVR-H3 containing the amino acid sequence of SEQ ID NO: 3, and a light chain variable region including HVR-L1 containing the amino acid sequence of SEQ ID NO: 4, HVR-L2 containing the amino acid sequence of SEQ ID NO: 5, and HVR-L3 containing the amino acid sequence of SEQ ID NO:

6.

2. The use of approximately 1,000 mg of anti-TIGIT monoclonal antibody in the manufacture of a drug for treating cancer in a subject requiring cancer treatment, wherein the drug is formulated for subcutaneous administration, and the anti-TIGIT monoclonal antibody is a full-length antibody comprising a heavy chain variable region including HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, HVR-H2 containing the amino acid sequence of SEQ ID NO: 2, and HVR-H3 containing the amino acid sequence of SEQ ID NO: 3, and a light chain variable region including HVR-L1 containing the amino acid sequence of SEQ ID NO: 4, HVR-L2 containing the amino acid sequence of SEQ ID NO: 5, and HVR-L3 containing the amino acid sequence of SEQ ID NO:

6.

3. An anti-TIGIT monoclonal antibody for use in the treatment of cancer in patients requiring cancer treatment, wherein the anti-TIGIT monoclonal antibody is a full-length antibody comprising a heavy chain variable region including HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, HVR-H2 containing the amino acid sequence of SEQ ID NO: 2, and HVR-H3 containing the amino acid sequence of SEQ ID NO: 3, and a light chain variable region including HVR-L1 containing the amino acid sequence of SEQ ID NO: 4, HVR-L2 containing the amino acid sequence of SEQ ID NO: 5, and HVR-L3 containing the amino acid sequence of SEQ ID NO: 6, and is administered subcutaneously at a dose of approximately 1,000 mg.

4. The method according to claim 1, the use according to claim 2, or the anti-TIGIT monoclonal antibody according to claim 3, wherein the anti-TIGIT monoclonal antibody is administered to the thigh or abdomen.

5. The method according to claim 1 or 4, the use according to claim 2 or 4, or the anti-TIGIT monoclonal antibody according to claim 3 or 4, wherein the anti-TIGIT monoclonal antibody is administered every three weeks (Q3W).

6. A method for treating cancer, comprising subcutaneously administering an anti-TIGIT monoclonal antibody at a dose of approximately 1,000 mg to a subject requiring cancer treatment, and administering an anti-PD-L1 monoclonal antibody at a dose of approximately 1,875 mg to approximately 2,000 mg to the subject, wherein the anti-TIGIT monoclonal antibody comprises a heavy chain variable region including HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, HVR-H2 containing the amino acid sequence of SEQ ID NO: 2, and HVR-H3 containing the amino acid sequence of SEQ ID NO: 3, and HVR-L1 containing the amino acid sequence of SEQ ID NO: 4, and amino acids of SEQ ID NO: 5 A method comprising a full-length antibody comprising a light chain variable region comprising HVR-L2 containing an acid sequence and HVR-L3 containing the amino acid sequence of SEQ ID NO: 6, wherein the anti-PD-L1 monoclonal antibody is a full-length antibody comprising a heavy chain variable region comprising HVR-H1 containing the amino acid sequence of SEQ ID NO: 10, HVR-H2 containing the amino acid sequence of SEQ ID NO: 11, and HVR-H3 containing the amino acid sequence of SEQ ID NO: 12, and a light chain variable region comprising HVR-L1 containing the amino acid sequence of SEQ ID NO: 13, HVR-L2 containing the amino acid sequence of SEQ ID NO: 14, and HVR-L3 containing the amino acid sequence of SEQ ID NO:

15.

7. The use of approximately 1,000 mg of anti-TIGIT monoclonal antibody and approximately 1,875 mg to approximately 2,000 mg of anti-PD-L1 monoclonal antibody in the manufacture of a drug for treating cancer in a patient requiring cancer treatment, wherein the drug is formulated for subcutaneous administration, and the anti-TIGIT monoclonal antibody comprises a heavy chain variable region including HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, HVR-H2 containing the amino acid sequence of SEQ ID NO: 2, and HVR-H3 containing the amino acid sequence of SEQ ID NO: 3, and HVR-L1 containing the amino acid sequence of SEQ ID NO: 4, and amino acids of SEQ ID NO: 5 The anti-PD-L1 monoclonal antibody is a full-length antibody comprising a light chain variable region comprising HVR-L2 containing an acid sequence and HVR-L3 containing the amino acid sequence of SEQ ID NO: 6, wherein the anti-PD-L1 monoclonal antibody is a full-length antibody comprising a heavy chain variable region comprising HVR-H1 containing the amino acid sequence of SEQ ID NO: 10, HVR-H2 containing the amino acid sequence of SEQ ID NO: 11, and HVR-H3 containing the amino acid sequence of SEQ ID NO: 12, and a light chain variable region comprising HVR-L1 containing the amino acid sequence of SEQ ID NO: 13, HVR-L2 containing the amino acid sequence of SEQ ID NO: 14, and HVR-L3 containing the amino acid sequence of SEQ ID NO:

15.

8. An anti-TIGIT monoclonal antibody and an anti-PD-L1 monoclonal antibody for use in the treatment of cancer in patients requiring cancer treatment, wherein the anti-TIGIT monoclonal antibody is a full-length antibody comprising a heavy chain variable region including HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, HVR-H2 containing the amino acid sequence of SEQ ID NO: 2, and HVR-H3 containing the amino acid sequence of SEQ ID NO: 3, and a light chain variable region including HVR-L1 containing the amino acid sequence of SEQ ID NO: 4, HVR-L2 containing the amino acid sequence of SEQ ID NO: 5, and HVR-L3 containing the amino acid sequence of SEQ ID NO: 6, and approximately 1,000 mg An anti-TIGIT monoclonal antibody and an anti-PD-L1 monoclonal antibody, administered subcutaneously in doses of approximately 1,875 mg to approximately 2,000 mg, wherein the anti-PD-L1 monoclonal antibody is a full-length antibody comprising a heavy chain variable region including HVR-H1 containing the amino acid sequence of SEQ ID NO: 10, HVR-H2 containing the amino acid sequence of SEQ ID NO: 11, and HVR-H3 containing the amino acid sequence of SEQ ID NO: 12, and a light chain variable region including HVR-L1 containing the amino acid sequence of SEQ ID NO: 13, HVR-L2 containing the amino acid sequence of SEQ ID NO: 14, and HVR-L3 containing the amino acid sequence of SEQ ID NO:

15.

9. The method according to claim 6, the use according to claim 7, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to claim 8, wherein the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are administered simultaneously.

10. The method according to claim 6 or 9, the use according to claim 7 or 9, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to claim 8 or 9, wherein the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are co-formulated.

11. The method according to claim 6 or 9, the use according to claim 7 or 9, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to claim 8 or 9, wherein the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed within 24 hours prior to administration to the subject.

12. The method, use, or anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to claim 11, wherein the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are mixed during administration to the subject.

13. The method according to claim 6, the use according to claim 7, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to claim 8, wherein the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are administered sequentially.

14. The method according to any one of claims 6 and 9 to 13, the use according to any one of claims 7 and 9 to 13, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 13, wherein the anti-PD-L1 monoclonal antibody is administered intravenously.

15. The method according to any one of claims 6 and 9 to 13, the use according to any one of claims 7 and 9 to 13, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 13, wherein the anti-PD-L1 monoclonal antibody is administered subcutaneously.

16. The method according to any one of claims 6 and 9 to 15, the use according to any one of claims 7 and 9 to 15, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 15, wherein the anti-TIGIT monoclonal antibody is administered every three weeks (Q3W).

17. The aforementioned cancers include lung cancer, non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, ureteral cancer, urethral cancer, colorectal cancer, colon cancer, rectal cancer, kidney cancer, sarcoma, ovarian cancer, breast cancer, cervical cancer, fallopian tube cancer, endometrial cancer, uterine cancer, pancreatic cancer, stomach cancer, bladder cancer, esophageal cancer, mesothelioma, melanoma, head and neck cancer, thyroid cancer, sarcoma, prostate cancer, penile cancer, glioblastoma, thymic cancer, esophageal cancer, nasopharyngeal cancer, mesothelioma, liver cancer, biliary tract cancer, HPV-positive cancer, leukemia, lymphoma, brain cancer, neuroendocrine cancer, myeloma, and mycosis. A method according to any one of claims 1, 4 to 6 and 9 to 16, selected from the group consisting of sarcomas, Merkel cell carcinoma, hematological malignancies, mismatch repair deficiency (dMMR) cancers, and high microsatellite instability (MSI-H) cancers; a use according to any one of claims 2, 4, 5, 7 and 9 to 16; an anti-TIGIT monoclonal antibody according to any one of claims 3 to 5; or an anti-TIGIT monoclonal antibody and an anti-PD-L1 monoclonal antibody according to any one of claims 8 to 16.

18. The aforementioned cancers include bladder cancer, muscle-invasive bladder cancer, urothelial carcinoma, ureteral cancer, ureteral urothelial carcinoma, urethral urothelial carcinoma, kidney cancer, renal pelvis cancer, renal cell carcinoma, clear cell kidney cancer, rectal cancer, colon cancer, colorectal cancer, sarcoma, osteosarcoma, leiomyosarcoma, pleomorphic sarcoma, myxofibrosarcoma, liposarcoma, chondrosarcoma, lung cancer, non-small cell lung cancer, fallopian tube cancer, peritoneal cancer, esophageal cancer, esophageal squamous cell carcinoma, mesothelioma, pleural mesothelioma, peritoneal mesothelioma, ovarian cancer, cervical cancer, cervical adenosquamous cell carcinoma, breast cancer, triple-negative breast cancer, H ER2-positive breast cancer, HER2-negative breast cancer, estrogen receptor-positive breast cancer, progesterone receptor-positive breast cancer, luminal type B breast cancer, lymphoma, T-cell lymphoma, B-cell lymphoma, nasal lymphoma, non-Hodgkin lymphoma, follicular lymphoma, penile cancer, prostate cancer, castration-resistant prostate cancer, endometrial cancer, uterine cancer, myeloma, multiple myeloma, head and neck cancer, prostate cancer, melanoma, cutaneous melanoma, Merkel cell carcinoma, pancreatic cancer, hepatocellular carcinoma, gastric cancer, gastroesophageal junction adenocarcinoma, glioblastoma, glioblastoma multiforme Mycosis fungoides, HPV-positive cancer, HPV-associated cervical cancer, HPV-associated anal squamous cell carcinoma, HPV-associated penile squamous cell carcinoma, HPV-associated vulvar squamous cell carcinoma, vulvar cancer, vaginal cancer, anal cancer, oropharyngeal cancer, oropharyngeal squamous cell carcinoma, leukemia, acute myeloid leukemia, bone cancer, solitary osteoplasmacytoma, squamous cell carcinoma, cutaneous squamous cell carcinoma, thyroid cancer, metastatic colorectal cancer without microsatellite stability / mismatch repair deficiency (MSS / pMMR), cancer with mismatch repair deficiency (dMMR), high frequency microsatellite A method according to any one of claims 1, 4 to 6 and 9 to 16, selected from the group consisting of crossatellite instability (MSI-H) cancer, nasal extranodal NK / T cell lymphoma, neuroendocrine cancer, biliary tract cancer, cholangiocarcinoma, and intrahepatic cholangiocarcinoma; a use according to any one of claims 2, 4, 5, 7 and 9 to 16; an anti-TIGIT monoclonal antibody according to any one of claims 3 to 5; or an anti-TIGIT monoclonal antibody and an anti-PD-L1 monoclonal antibody according to any one of claims 8 to 16.

19. The method according to any one of claims 1, 4 to 6 and 9 to 16, wherein the cancer is selected from the group consisting of Merkel cell carcinoma, urothelial carcinoma, renal cell carcinoma, non-small cell lung cancer, breast cancer, triple-negative breast cancer, hepatocellular carcinoma, melanoma, Hodgkin lymphoma, head and neck cancer, colorectal cancer, gastric cancer, cervical cancer, mediastinal B-cell large cell lymphoma, cutaneous squamous cell carcinoma, basal cell carcinoma, bladder cancer, endometrial cancer, esophageal cancer, malignant pleural mesothelioma, cancers with high tumor mutation burden (TMB), cancers with mismatch repair deficiency (dMMR), and cancers with high microsatellite instability (MSI-H); the use according to any one of claims 2, 4, 5, 7 and 9 to 16; the anti-TIGIT monoclonal antibody according to any one of claims 3 to 5; or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 16.

20. The aforementioned cancers include lung cancer, non-small cell lung cancer, bronchogenic lung cancer, breast cancer, triple-negative breast cancer, estrogen receptor-positive breast cancer, HER2-positive breast cancer, metastatic lobular breast cancer, ductal carcinoma, cervical cancer, fallopian tube cancer, serous adenocarcinoma of the fallopian tube, ovarian cancer, ovarian endometrioid tumor, serous adenocarcinoma of the ovary, mucinous carcinoma of the ovary, uterine cancer, endometrial cancer, skin cancer, melanoma, cutaneous melanoma, Merkel cell carcinoma, head and neck cancer, squamous cell carcinoma of the head and neck, hematological malignancies, leukemia, myeloid leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, myelomonocytic leukemia, thyroid cancer, and thyroid cancer. Cancer, thymic carcinoma, neuroendocrine carcinoma, chromaffin cell tumor, glioma, glioblastoma multiforme, paraganglioma, lymphoma, B-cell lymphoma, Hodgkin lymphoma, B-cell non-Hodgkin lymphoma, non-Hodgkin lymphoma, cutaneous T-cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, marginal lymphoma, pancreatic cancer, pancreatic ductal adenocarcinoma, rectal cancer, colon cancer, colorectal cancer, urinary tract cancer, urogenital cancer, mesothelioma, pleural mesothelioma, peritoneal mesothelioma, sarcoma, chondrosarcoma, clear cell sarcoma, liposarcoma, myxoid / round cell liposarcoma, synovial sarcoma, hydatidiform soft part sarcoma, gliosarcoma, uterine Sarcoma, kidney cancer, non-clear cell kidney cancer, renal cell carcinoma, bladder cancer, urothelial carcinoma, muscle-invasive bladder cancer, non-muscle-invasive bladder cancer, HER2-positive bladder cancer, gallbladder cancer, stomach cancer, esophageal cancer, esophageal squamous cell carcinoma, gastrointestinal cancer, gastroesophageal cancer, gastroesophageal junction cancer, HER2-positive stomach cancer, primary peritoneal cancer, cutaneous squamous cell carcinoma, prostate cancer, prostate adenocarcinoma, castration-resistant prostate cancer, urogenital cancer, ureteral urothelial carcinoma, renal pelvis urothelial carcinoma, urethral urothelial carcinoma, appendiceal cancer, penile cancer, anal canal cancer, hepatocellular carcinoma, hepatobiliary tract cancer, unresectable liver and intrahepatic bile duct cancer, biliary tract A method according to any one of claims 1, 4 to 6 and 9 to 16, selected from the group consisting of cancer, bile duct cancer, intrahepatic bile duct cancer, extrahepatic bile duct cancer, HPV-related cancer, HPV-related anal squamous cell carcinoma, HPV-related cervical squamous cell carcinoma, HPV-related penile squamous cell carcinoma, HPV-related vulvar squamous cell carcinoma, nasopharyngeal cancer, upper pharyngeal cancer, pharyngeal squamous cell carcinoma, hypopharyngeal squamous cell carcinoma, oral squamous cell carcinoma, and mycosis fungoides; a use according to any one of claims 2, 4, 5, 7 and 9 to 16; an anti-TIGIT monoclonal antibody according to any one of claims 3 to 5;Or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 16.

21. The method according to any one of claims 1, 4 to 6 and 9 to 16, wherein the cancer is selected from the group consisting of urothelial carcinoma, non-small cell lung cancer (NSCLC), breast cancer, triple-negative breast cancer, hepatocellular carcinoma, and melanoma; the use according to any one of claims 2, 4, 5, 7 and 9 to 16; the anti-TIGIT monoclonal antibody according to any one of claims 3 to 5; or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 16.

22. The method according to any one of claims 1, 4 to 6 and 9 to 16, wherein the cancer is selected from the group consisting of multiple myeloma, cervical cancer, esophageal cancer, esophageal squamous cell carcinoma, lung cancer, non-small cell lung cancer, glioblastoma, endometrial cancer, ovarian cancer, squamous cell carcinoma, and head and neck cancer; the use according to any one of claims 2, 4, 5, 7 and 9 to 16; the anti-TIGIT monoclonal antibody according to any one of claims 3 to 5; or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 16.

23. The method according to any one of claims 1, 4 to 6 and 9 to 16, wherein the cancer is selected from the group consisting of cervical cancer, head and neck squamous cell carcinoma, head and neck cancer, non-small cell lung cancer, non-squamous non-small cell lung cancer, esophageal squamous cell carcinoma, esophageal cancer, breast cancer, triple-negative breast cancer, gastric cancer, gastroesophageal junction adenocarcinoma, multiple myeloma, non-Hodgkin lymphoma, B-cell lymphoma, liver cancer, bladder cancer, urothelial carcinoma, pancreatic cancer, and pancreatic adenocarcinoma, wherein the method according to any one of claims 1, 4 to 6 and 9 to 16, the use according to any one of claims 2, 4, 5, 7 and 9 to 16, the anti-TIGIT monoclonal antibody according to any one of claims 3 to 5, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 16.

24. The method according to any one of claims 1, 4 to 6 and 9 to 16, wherein the cancer is a solid tumor, the use according to any one of claims 2, 4, 5, 7 and 9 to 16, the anti-TIGIT monoclonal antibody according to any one of claims 3 to 5, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 16.

25. The method according to any one of claims 1, 4 to 6 and 9 to 16, wherein the cancer is a blood cancer, the use according to any one of claims 2, 4, 5, 7 and 9 to 16, the anti-TIGIT monoclonal antibody according to any one of claims 3 to 5, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 16.

26. The method according to any one of claims 6 and 9 to 25, the use according to any one of claims 7 and 9 to 25, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 25, wherein the heavy chain variable region of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO:

16.

27. The method according to any one of claims 6 and 9 to 26, the use according to any one of claims 7 and 9 to 26, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 26, wherein the light chain variable region of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO:

17.

28. The method according to any one of claims 6 and 9 to 27, wherein the heavy chain variable region of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 16, and the light chain variable region of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 17, the use according to any one of claims 7 and 9 to 27, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 27.

29. The method according to any one of claims 6 and 9 to 28, wherein the anti-PD-L1 monoclonal antibody is an IgG antibody, the use according to any one of claims 7 and 9 to 28, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 28.

30. The method, use, or anti-TIGIT monoclonal antibody and anti-PD-L1 antibody according to claim 29, wherein the anti-PD-L1 monoclonal antibody is an IgG1 antibody or an IgG4 antibody.

31. The method according to any one of claims 6 and 9 to 30, wherein the anti-PD-L1 monoclonal antibody or the anti-TIGIT monoclonal antibody is a human antibody, the use according to any one of claims 7 and 9 to 30, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 30.

32. The method according to any one of claims 6 and 9 to 30, wherein the anti-PD-L1 monoclonal antibody or the anti-TIGIT monoclonal antibody is a humanized antibody, the use according to any one of claims 7 and 9 to 30, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 30.

33. The method according to any one of claims 6 and 9 to 30, the use according to any one of claims 7 and 9 to 30, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 30, wherein the anti-PD-L1 monoclonal antibody is selected from the group consisting of atezolizumab (MPDL3280A), durvalumab (MEDI4736), avelumab, and MDX-1105.

34. The method according to any one of claims 1, 4 to 6 and 9 to 33, wherein the heavy chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 7 or SEQ ID NO: 8; the use according to any one of claims 2, 4, 5, 7 and 9 to 33; the anti-TIGIT monoclonal antibody according to any one of claims 3 to 5 and 17 to 25; or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 33.

35. The method according to any one of claims 1, 4 to 6 and 9 to 34, wherein the light chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 9; the use according to any one of claims 2, 4, 5, 7 and 9 to 34; the anti-TIGIT monoclonal antibody according to any one of claims 3 to 5, 17 to 25 and 34; or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 34.

36. The method according to any one of claims 1, 4 to 6 and 9 to 35, wherein the heavy chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 7 or SEQ ID NO: 8, and the light chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 9; the use according to any one of claims 2, 4, 5, 7 and 9 to 35; the anti-TIGIT monoclonal antibody according to any one of claims 3 to 5, 17 to 25 and 34 to 35; or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 35.

37. The method according to any one of claims 1, 4 to 6 and 9 to 36, wherein the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; the use according to any one of claims 2, 4, 5, 7 and 9 to 36; the anti-TIGIT monoclonal antibody according to any one of claims 3 to 5, 17 to 25 and 34 to 36; or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 36.

38. The method according to any one of claims 1, 4 to 6 and 9 to 37, wherein the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 19 or SEQ ID NO: 25; the use according to any one of claims 2, 4, 5, 7 and 9 to 37; the anti-TIGIT monoclonal antibody according to any one of claims 3 to 5, 17 to 25 and 34 to 37; or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 37.

39. The method according to any one of claims 1, 4 to 6 and 9 to 38, wherein the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20; the use according to any one of claims 2, 4, 5, 7 and 9 to 38; the anti-TIGIT monoclonal antibody according to any one of claims 3 to 5, 17 to 25 and 34 to 38; or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 38.

40. The method according to any one of claims 1, 4 to 6 and 9 to 39, wherein the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24, and the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20; the use according to any one of claims 2, 4, 5, 7 and 9 to 39; the anti-TIGIT monoclonal antibody according to any one of claims 3 to 5, 17 to 25 and 34 to 39; or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 39.

41. The method according to any one of claims 1, 4 to 6 and 9 to 39, wherein the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 19 or SEQ ID NO: 25, and the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20; the use according to any one of claims 2, 4, 5, 7 and 9 to 39; the anti-TIGIT monoclonal antibody according to any one of claims 3 to 5, 17 to 25 and 34 to 39; or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 39.

42. The method according to any one of claims 1, 4 to 6 and 9 to 41, wherein the anti-TIGIT monoclonal antibody is an IgG antibody; the use according to any one of claims 2, 4, 5, 7 and 9 to 41; the anti-TIGIT monoclonal antibody according to any one of claims 3 to 5, 17 to 25 and 34 to 41; or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 41.

43. The method according to claim 42, use of an anti-TIGIT monoclonal antibody, or an anti-TIGIT monoclonal antibody and an anti-PD-L1 monoclonal antibody, wherein the anti-TIGIT monoclonal antibody is an IgG1 antibody or an IgG4 antibody.

44. The method according to any one of claims 1, 4 to 6 and 9 to 43, wherein the anti-TIGIT monoclonal antibody is a human antibody; the use according to any one of claims 2, 4, 5, 7 and 9 to 43; the anti-TIGIT monoclonal antibody according to any one of claims 3 to 5, 17 to 25 and 34 to 43; or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 43.

45. The method according to any one of claims 1, 4 to 6 and 9 to 43, wherein the anti-TIGIT monoclonal antibody is a humanized antibody; the use according to any one of claims 2, 4, 5, 7 and 9 to 43; the anti-TIGIT monoclonal antibody according to any one of claims 3 to 5, 17 to 25 and 34 to 43; or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 43.

46. The method according to any one of claims 1, 4 to 6 and 9 to 43, wherein the anti-TIGIT monoclonal antibody inhibits or blocks the interaction between CD226 and TIGIT; the use according to any one of claims 2, 4, 5, 7 and 9 to 43; the anti-TIGIT monoclonal antibody according to any one of claims 3 to 5, 17 to 25 and 34 to 43; or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 43.

47. The method according to any one of claims 1, 4 to 6 and 9 to 43, wherein the anti-TIGIT monoclonal antibody is tiragolumab; the use according to any one of claims 2, 4, 5, 7 and 9 to 43; the anti-TIGIT monoclonal antibody according to any one of claims 3 to 5, 17 to 25 and 34 to 43; or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 43.

48. The method according to any one of claims 1, 4 to 6 and 9 to 47, wherein the anti-TIGIT monoclonal antibody is present in a liquid pharmaceutical composition comprising 160 mg / mL tiragolumab and 2000 U / mL hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.5; the use according to any one of claims 2, 4, 5, 7 and 9 to 47; the anti-TIGIT monoclonal antibody according to any one of claims 3 to 5, 17 to 25 and 34 to 47; or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 47.

49. The method according to any one of claims 6 and 9 to 47, wherein the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are present in a liquid pharmaceutical preparation containing 40 mg / ml tilagolumab, 80 mg / ml atezolizumab, and 2000 U / ml hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.8, the use according to any one of claims 7 and 9 to 47, or the anti-TIGIT monoclonal antibody and anti-PD-L1 monoclonal antibody according to any one of claims 8 to 47.

50. A manufactured product containing a formulation with 1,000 mg of tiragolumab.

51. The manufactured product according to claim 50, wherein the preparation further comprises 1,875 mg or 2,000 mg of atezolizumab.

52. The manufactured product according to claim 50, wherein the preparation further comprises 1,875 mg of atezolizumab.

53. The manufactured product according to claim 50, wherein the preparation further comprises 2,000 mg of atezolizumab.

54. The manufactured product according to any one of claims 50 to 53, further comprising hyaluronidase.

55. A manufactured product containing a formulation comprising 1,000 mg of tiragolumab and 1,875 mg or 2,000 mg of atezolizumab.

56. The manufactured product according to claim 55, wherein the formulation comprises 1,875 mg of atezolizumab.

57. The manufactured product according to claim 55, wherein the formulation comprises 2,000 mg of atezolizumab.

58. The manufactured product according to any one of claims 55 to 57, further comprising hyaluronidase.

59. The manufactured product according to claim 54 or 58, wherein the concentration of the hyaluronidase is 2000 U / mL.

60. The manufactured product according to any one of claims 54 and 58 to 59, wherein the hyaluronidase is recombinant human hyaluronidase.

61. The manufactured product according to claim 60, wherein the recombinant hyaluronidase is a human soluble pH20 hyaluronidase glycoprotein such as rHuPH20.

62. The manufactured product according to any one of claims 50 to 61, wherein the manufactured product is a vial.

63. The manufactured product according to claim 62, wherein the vial is a single-dose vial.

64. The manufactured product according to claim 62 or 63, wherein the vial is sealed with a chlorobutyl elastomer stopper.

65. The manufactured product according to any one of claims 50 to 61, wherein the manufactured product is a pre-filled syringe.

66. The manufactured product according to any one of claims 50 to 61, wherein the manufactured product is a syringe pump.

67. The manufactured product according to any one of claims 50 to 61, wherein the manufactured product is a subcutaneous administration device.

68. The manufactured product according to claim 67, wherein the subcutaneous administration device is selected from the group consisting of a syringe, syringe pump, injection device, drip pump, syringe pen, needleless device, auto-injector, and subcutaneous patch delivery system.

69. A manufactured product comprising a subcutaneous administration device, wherein the subcutaneous administration device contains a fixed dose of 1,000 mg of tiragolumab and delivers it to a patient.

70. The manufactured product according to claim 69, wherein the subcutaneous administration device further contains a fixed dose of 1,875 mg or 2,000 mg of atezolizumab and delivers it to the patient.

71. The manufactured product according to claim 70, wherein the subcutaneous administration device further contains a fixed dose of 1,875 mg of atezolizumab and delivers it to the patient.

72. The manufactured product according to claim 70, wherein the subcutaneous administration device further contains a fixed dose of 2,000 mg of atezolizumab and delivers it to the patient.

73. The manufactured product according to any one of claims 69 to 72, wherein the subcutaneous administration device further contains hyaluronidase and delivers it to the patient.

74. The manufactured product according to claim 73, wherein the hyaluronidase is a human soluble pH20 hyaluronidase glycoprotein such as rHuPH20.

75. The manufactured product according to any one of claims 69 to 74, wherein the subcutaneous administration device is selected from the group consisting of a syringe, a syringe pump, an injection device, an infusion pump, a syringe pen, a needleless device, an auto-injector, and a subcutaneous patch delivery system.

76. The manufactured product according to any one of claims 69 to 75, wherein the subcutaneous administration device is a syringe.

77. The manufactured product according to any one of claims 69 to 75, wherein the subcutaneous administration device is a syringe pump.

78. The manufactured product according to any one of claims 50 to 77, wherein the manufactured product comprises approximately 3 mL to approximately 60 mL of anti-TIGIT full-length monoclonal antibody and one or more of hyaluronidase, histidine buffer, sucrose, and polysorbate 20.

79. The manufactured product according to claim 78, wherein the manufactured product comprises about 10 mL of tilagolumab and one or more of hyaluronidase, histidine buffer, sucrose, and polysorbate 20.

80. The manufactured product according to claim 78, wherein the manufactured product comprises about 7 mL of tilagolumab and one or more of hyaluronidase, histidine buffer, sucrose, and polysorbate 20.

81. The manufactured product according to claim 78, wherein the manufactured product comprises approximately 6.5 mL of tilagolmab and one or more of hyaluronidase, histidine buffer, sucrose, and polysorbate 20.

82. The manufactured product according to claim 78, wherein the manufactured product comprises about 21 mL of tilagolmab and one or more of hyaluronidase, histidine buffer, sucrose, and polysorbate 20.

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