USO DE ANTAGONISTA DE LAG-3, COMPOSIÇÃO, KIT, E COMBINAÇÃO

Description

USE OF LAG-3 ANTAGONIST, COMPOSITION, KIT, AND COMBINATION Separated from BR112023006783-9, filed on 10 / 22 / 2021. CROSS-REFERENCE TO RELATED REQUESTS

[001] This PCT application claims the priority benefit of U.S. Provisional Applications No. 63 / 104,744, filed October 23, 2020, and No. 63 / 110,210, filed November 5, 2020, which are incorporated herein by reference in their entirety. Reference to the sequence list sent electronically via EFS-Web

[002] The contents of the electronically submitted sequence listing (Name: 3338_240PC02_Seqlisting_ST25.txt; Size: 94,766 Bytes; and Creation Date: October 21, 2021) are incorporated herein by reference in their entirety. FIELD OF INVENTION

[003] The present invention relates to methods of treating humans affected with lung cancer comprising a lymphocyte activation gene 3 (LAG-3) antagonist. BACKGROUND OF THE INVENTION

[004] Lung cancer, and particularly non-small cell lung cancer (NSCLC), remains the leading cause of cancer-related mortality worldwide, accounting for approximately 18% of all cancer deaths (Jenal A, et al., CA Cancer J. Clin. 2011; 61:69-90).

[005] Until recently, the treatment of patients with advanced NSCLC whose tumors did not exhibit targetable genetic alterations was solely cytotoxic chemotherapy. Despite treatment, patients with metastatic NSCLC treated with platinum-based dual chemotherapy had a median survival of approximately 10 months and a 5-year survival rate of less than 5%. The introduction Petition 870260055013, dated 08 / 06 / 2026, page 7 / 490 2 / 189 of immune checkpoint inhibitors targeting the PD-1 signaling pathway in the treatment of NSCLC patients had a significant effect on patient survival. The anti-PD-1 antibody pembrolizumab combined with first-line chemotherapy demonstrated an improvement in overall survival in NSCLC patients compared to chemotherapy alone (Gandhi L, et al., N. Engl. J. Med. 2018; 378:2078-2092; Paz-Ares L, et al., N. Engl. J. Med. 2018;379:2040-2051). More recently, the anti-PD-1 antibody nivolumab plus the anti-CTLA-4 antibody ipilimumab, as well as nivolumab plus ipilimumab in combination with chemotherapy, have also shown benefits over chemotherapy in this setting (Peters S, et al., Annals of Oncology 2019;30 (suppl_5):v851-v934; Reck M, J. Clin. Oncol. 2020; (suppl):abstr. 9501). However, despite these advances, the median survival of first-line patients with metastatic NSCLC is approximately 22 months in the non-squamous population and 15.9 months in the squamous population (Paz-Ares L, et al.; Gadgeel S, et al., J. Clin. Oncol. 2020;38(14):1505-1517).

[006] There is a need for improved methods for treating humans with lung cancer. SUMMARY OF THE INVENTION

[007] The present invention is directed to a method of treating a human individual with lung cancer, the method comprising administering to the individual a lymphocyte activating gene 3 (LAG-3) antagonist and a platinum double chemotherapy (PDCT).

[008] In some respects, the method is a first-line therapy.

[009] In some respects, the method is a second-line therapy.

[0010] In some respects, the method is a third-generation therapy. Petition 870260055013, dated 08 / 06 / 2026, page 8 / 490 3 / 189 line.

[0011] In some respects, the individual has progressed in a previous therapy.

[0012] In some respects, lung cancer is recurrent after multimodal therapy for locally advanced lung cancer.

[0013] In some respects, the individual has not received prior systemic therapy for cancer, the individual has not received prior systemic therapy for lung cancer, or the individual has not received prior systemic therapy for advanced or metastatic lung cancer.

[0014] In some respects, the individual is naive to previous immuno-oncological therapy, the individual is naive to previous immuno-oncological therapy for lung cancer, or lung cancer is naive to previous immuno-oncological therapy.

[0015] In some respects, lung cancer is unresectable, advanced, recurrent, and / or metastatic.

[0016] In some respects, the individual suffers from stage IV lung cancer.

[0017] In some respects, lung cancer is a small cell lung cancer.

[0018] In some respects, lung cancer is non-small cell lung cancer (NSCLC). In some respects, NSCLC has a squamous or non-squamous histology.

[0019] In some respects, one or more immune cells in the individual's tumor tissue express LAG-3. In some respects, at least about 1%, at least about 3%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least Petition 870260055013, dated 08 / 06 / 2026, page 9 / 490 4 / 189 in about 70%, at least about 80%, at least about 90%, or about 100% of immune cells express LAG-3. In some respects, at least about 1% of immune cells express LAG-3. In some respects, immune cells are tumor-infiltrating lymphocytes. In some respects, tumor-infiltrating lymphocytes are CD8+ cells.

[0020] In some respects, one or more tumor cells in the individual's tumor tissue express PD-L1. In some respects, at least about 1%, at least about 3%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or about 100% of the tumor cells express PD-L1. In some respects, at least about 1% of the tumor cells express PD-L1.

[0021] In some respects, the LAG-3 antagonist is an anti-LAG-3 antibody.

[0022] In some respects, the anti-LAG-3 antibody is a full-length antibody.

[0023] In some respects, the anti-LAG-3 antibody is a monoclonal, human, humanized, chimeric, or multispecific antibody. In some respects, the multispecific antibody is a dual-affinity redirecting antibody (DART), a DVD-Ig, or a bispecific antibody.

[0024] In some respects, the anti-LAG-3 antibody is an F(ab')2 fragment, a Fab' fragment, a Fab fragment, an Fv fragment, an scFv fragment, a dsFv fragment, a dAb fragment, or a single chain of linking polypeptide. Petition 870260055013, dated 08 / 06 / 2026, page 10 / 490 5 / 189

[0025] In some respects, the anti-LAG-3 antibody is BMS-986016 (relatlimab), IMP731 (H5L7BW), MK4280 (28G-10, favezelimab), REGN3767 (fianlimab), GSK2831781, humanized BAP050, IMP-701 (LAG525, ieramilimab), aLAG3(0414), aLAG3(0416), Sym022, TSR033, TSR-075, XmAb841 (XmAb22841), MGD013 (tebotelimab), BI754111, FS118, P 13B02-30, AVA-017, 25F7, AGEN1746, RO7247669, INCAGN02385, IBI-110, EMB-02, IBI-323, LBL-007, ABL501, or comprises an antigen-binding portion thereof.

[0026] In some respects, the anti-LAG-3 antibody comprises CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence shown in SEQ ID No:3 and CDR1, CDR2 and CDR3 domains of the variable light chain region with the sequence shown in SEQ ID No:4.

[0027] In some respects, the anti-LAG-3 antibody comprises: (a) a variable region heavy chain CDR1 comprising the sequence presented in SEQ ID No:5; (b) a variable region heavy chain CDR2 comprising the sequence presented in SEQ ID No:6; (c) a variable region heavy chain CDR3 comprising the sequence presented in SEQ ID No:7; (d) a variable region light chain CDR1 comprising the sequence presented in SEQ ID No:8; (e) a variable region light chain CDR2 comprising the sequence presented in SEQ ID No:9; and (f) a variable region light chain CDR3 comprising the sequence presented in SEQ ID No:10.

[0028] In some respects, the anti-LAG-3 antibody comprises variable heavy and light chain regions comprising the sequences presented in SEQ ID Nos. 3 and 4, respectively.

[0029] In some respects, the anti-LAG-3 antibody comprises heavy and light chains comprising the sequences shown Petition 870260055013, dated 08 / 06 / 2026, p. 11 / 490 6 / 189 in SEQ ID No. 1 and 2, respectively.

[0030] In some respects, the anti-LAG-3 antibody comprises heavy and light chains comprising the sequences presented in SEQ ID Nos. 21 and 2, respectively.

[0031] In some respects, the LAG-3 antagonist is a soluble LAG-3 polypeptide. In some respects, the soluble LAG-3 polypeptide is a fusion polypeptide. In some respects, the soluble LAG-3 polypeptide comprises a ligand-binding fragment of the LAG-3 extracellular domain. In some respects, the ligand-binding fragment of the LAG-3 extracellular domain comprises an amino acid sequence with at least about 90%, at least about 95%, at least about 98%, at least about 99%, or about 100% sequence identity to SEQ ID No.:22. In some respects, the soluble LAG-3 polypeptide further comprises a half-life extension portion.In some respects, the half-life extension portion comprises a constant region of immunoglobulin or a portion thereof, an immunoglobulin-binding polypeptide, immunoglobulin G (IgG), albumin-binding polypeptide (ABP), a PASylation portion, a HESylation portion, XTEN, a PEGlylation portion, an Fc region, or any combination thereof. In some respects, the soluble LAG-3 polypeptide is IMP321 (ephtilagimod alfa).

[0032] In some respects, the LAG-3 antagonist is formulated for intravenous administration.

[0033] In some respects, the LAG-3 antagonist is administered at a fixed dose.

[0034] In some respects, the LAG-3 antagonist is administered at a dose of at least about 0.25 mg to about 2,000 mg, about 0.25 mg to about 1,600 mg, about 0.25 mg to about 1,200 mg, about 0.25 mg to about 800 mg, about 0.25 mg to Petition 870260055013, dated 08 / 06 / 2026, page 12 / 490 7 / 189 about 400 mg, about 0.25 mg to about 100 mg, about 0.25 mg to about 50 mg, about 0.25 mg to about 40 mg, about 0.25 mg to about 30 mg, about 0.25 mg to about 20 mg, about 20 mg to about 2000 mg, about 20 mg to about 1600 mg, about 20 mg to about 1200 mg, about 20 mg to about 800 mg, about 20 mg to about 400 mg, about 20 mg to about 100 mg, about 100 mg to about 2000 mg, about 100 mg to about 1800 mg, about 100 mg to about 1600 mg, about 100 mg to about 1400 mg, about 100 mg to about 1200 mg, about 100 mg to about 1000 mg, about 100 mg to about 800 mg, about 100 mg to about 600 mg, about 100 mg to about 400 mg, about 400 mg to about 2000 mg, about 400 mg to about 1800 mg, about 400 mg to about 1600 mg, about 400 mg to about 1400 mg, about 400 mg to about 1200 mg, or about 400 mg to about 1000 mg.

[0035] In some aspects, the LAG-3 antagonist is administered in a dose of approximately 0.25 mg, approximately 0.5 mg, approximately 0.75 mg, approximately 1 mg, approximately 1.25 mg, approximately 1.5 mg, approximately 1.75 mg, approximately 2 mg, approximately 2.25 mg, approximately 2.5 mg, approximately 2.75 mg, approximately 3 mg, approximately 3.25 mg, approximately 3.5 mg, approximately 3.75 mg, approximately 4 mg, approximately 4.25 mg, approximately 4.5 mg, approximately 4.75 mg, approximately 5 mg, approximately 5.25 mg, approximately 5.5 mg, approximately 5.75 mg, approximately 6 mg, approximately 6.25 mg, approximately 6.5 mg, approximately 6.75 mg, approximately 7 mg, approximately 7.25 mg, approximately 7.5 mg, approximately 7.75 mg, approximately 8 mg, approximately 8.25 mg, approximately 8.5 mg, approximately 8.75 mg, approximately 9 mg, approximately 9.25 mg, approximately 9.5 mg, approximately 9.75 mg, approximately 10 mg, approximately 20 mg, approximately 30 mg, approximately 40 mg, approximately 50 mg, approximately 60 mg, approximately 70 mg, approximately 80 mg, approximately 90 mg, approximately 100 mg, approximately 110 mg, approximately 120 mg, approximately 130 mg, approximately 140 mg, approximately 150 mg, approximately 160 mg Petition 870260055013, dated 08 / 06 / 2026, page 13 / 490 8 / 189 mg, about 170 mg, about 180 mg, about 190 mg, about 200 mg, about 210 mg, about 220 mg, about 230 mg, about 240 mg, about 250 mg, about 260 mg, about 270 mg, about 280 mg, about 290 mg, about 300 mg, about 310 mg, about 320 mg, about 330 mg, about 340 mg, about 350 mg, about 360 mg, about 370 mg, about 380 mg, about 390 mg, approximately 400 mg, approximately 410 mg, approximately 420 mg, approximately 430 mg, approximately 440 mg, approximately 450 mg, approximately 460 mg, approximately 470 mg, approximately 480 mg, approximately 490 mg, approximately 500 mg, approximately 510 mg, approximately 520 mg, approximately 530 mg, approximately 540 mg, approximately 550 mg, approximately 560 mg, approximately 570 mg, approximately 580 mg, approximately 590 mg, approximately 600 mg, approximately 610 mg, approximately 620 mg, approximately 630 mg, approximately 640 mg, approximately 650 mg, approximately 660 mg, approximately 670 mg, approximately 680 mg, approximately 690 mg approximately 700 mg, approximately 710 mg, approximately 720 mg, approximately 730 mg, approximately 740 mg, approximately 750 mg, approximately 760 mg, approximately 770 mg, approximately 780 mg, approximately 790 mg, approximately 800 mg, approximately 810 mg, approximately 820 mg, approximately 830 mg, approximately 840 mg, approximately 850 mg, approximately 860 mg, approximately 870 mg, approximately 880 mg, approximately 890 mg, approximately 900 mg, approximately 910 mg, approximately 920 mg, approximately 930 mg, approximately 940 mg, approximately 950 mg, approximately 960 mg, approximately 970 mgabout 980 mg, about 990 mg, about 1000 mg, about 1040 mg, about 1080 mg, about 1100 mg, about 1140 mg, about 1180 mg, about 1200 mg, about, 1240 mg, about 1280 mg, about 1300 mg, about 1340 mg, about 1380 mg, about 1400 mg, about 1440 mg, about 1480 mg, about 1500 mg, about 1540 mg, about 1580 mg, about 1600 mg, about 1640 mg, about 1680 mg, about 1700 mg, about 1740 mg, about 1780 mg, about 1800 mg, about 1840 mg, about 1880 mg, about 1900 mg, about Petition 870260055013, dated 08 / 06 / 2026, page 14 / 490 9 / 189 1940 mg, approximately 1980 mg, or approximately 2000 mg.

[0036] In some respects, the LAG-3 antagonist is administered at a weight-based dose.

[0037] In some respects, the LAG-3 antagonist is administered at a dose of approximately 0.003 mg / kg to approximately 25 mg / kg, approximately 0.003 mg / kg to approximately 20 mg / kg, approximately 0.003 mg / kg to approximately 15 mg / kg, approximately 0.003 mg / kg to approximately 10 mg / kg, approximately 0.003 mg / kg to approximately 5 mg / kg, approximately 0.003 mg / kg to approximately 1 mg / kg, approximately 0.003 mg / kg to approximately 0.9 mg / kg, approximately 0.003 mg / kg to approximately 0.8 mg / kg, approximately 0.003 mg / kg to approximately 0.7 mg / kg, approximately 0.003 mg / kg to approximately 0.6 mg / kg, approximately 0.003 mg / kg to about 0.5 mg / kg, about 0.003 mg / kg to about 0.4 mg / kg, about 0.003 mg / kg to about 0.3 mg / kg, about 0.003 mg / kg to about 0.2 mg / kg, about 0.003 mg / kg to about 0.1 mg / kg, about 0.1 mg / kg to about 25 mg / kg, about 0.1 mg / kg to about 20 mg / kg, about 0.1 mg / kg to about 15 mg / kg, about 0.1 mg / kg to about 10 mg / kg, about 0.1 mg / kg to about 5 mg / kg, about 0.1 mg / kg to about 1 mg / kg, about 1 mg / kg to about 25 mg / kg,about 1 mg / kg to about 20 mg / kg, about 1 mg / kg to about 15 mg / kg, about 1 mg / kg to about 10 mg / kg, about 1 mg / kg to about 5 mg / kg, about 5 mg / kg to about 25 mg / kg, about 5 mg / kg to about 20 mg / kg, about 5 mg / kg to about 15 mg / kg, about 5 mg / kg to about 10 mg / kg, about 10 mg / kg to about 25 mg / kg, about 10 mg / kg to about 20 mg / kg, about 10 mg / kg to about 15 mg / kg, about 15 mg / kg to about 25 mg / kg, about 15 mg / kg to about 20 mg / kg, or about 20 mg / kg to about 25 mg / kg.

[0038] In some respects, the LAG-3 antagonist is administered at a dose of approximately 0.003 mg / kg, approximately 0.004 mg / kg, approximately 0.005 mg / kg, approximately 0.006 mg / kg, approximately 0.007 mg / kg, approximately 0.008 mg / kg, approximately 0.009 mg / kg, approximately 0.01 mg / kg, approximately Petition 870260055013, dated 08 / 06 / 2026, page 15 / 490 10 / 189 0.02 mg / kg, approximately 0.03 mg / kg, approximately 0.04 mg / kg, approximately 0.05 mg / kg, approximately 0.06 mg / kg, approximately 0.07 mg / kg, approximately 0.08 mg / kg, approximately 0.09 mg / kg, approximately 0.1 mg / kg, approximately 0.2 mg / kg, approximately 0.3 mg / kg, approximately 0.4 mg / kg, approximately 0.5 mg / kg, approximately 0.6 mg / kg, approximately 0.7 mg / kg, approximately 0.8 mg / kg, approximately 0.9 mg / kg, approximately 1.0 mg / kg, approximately 2.0 mg / kg, approximately 3.0 mg / kg, approximately 4.0 mg / kg, approximately 5.0 mg / kg, approximately 6.0 mg / kg, approximately 7.0 mg / kg about 8.0 mg / kg, about 9.0 mg / kg, about 10.0 mg / kg, about 11.0 mg / kg, about 12.0 mg / kg, about 13.0 mg / kg, about 14.0 mg / kg, about 15.0 mg / kg, about 16.0 mg / kg, about 17.0 mg / kg, about 18.0 mg / kg, about 19.0 mg / kg, about 20.0 mg / kg, about 21.0 mg / kg, about 22.0 mg / kg, about 23.0 mg / kg, about 24.0 mg / kg or about 25.0 mg / kg.

[0039] In some aspects, the dose is administered once every week, once every two weeks, once every three weeks, once every four weeks, once every five weeks, once every six weeks, once every seven weeks, once every eight weeks, once every nine weeks, once every ten weeks, once every eleven weeks, or once every twelve weeks.

[0040] In some respects, PDCT comprises a platinum agent in combination with a nucleoside analogue, an antimetabolite, a taxane, a vinca alkaloid, or a topoisomerase inhibitor. In some respects, the platinum agent is cisplatin, carboplatin, oxaliplatin, satraplatin, picoplatin, nedaplatin, triplatin, lipoplatin, or phenantriplatin. In some respects, the platinum agent is cisplatin. In some respects, the platinum agent is carboplatin. In some respects, the nucleoside analogue is cytarabine, gemcitabine, lamivudine, entecavir, or telbivudine. In some respects, the analogue Petition 870260055013, dated 08 / 06 / 2026, page 16 / 490 11 / 189 of the nucleoside is gemcitabine. In some aspects, the antimetabolite is capecitabine, cladribine, clofarabine, cytarabine, floxuridine, fludarabine, fluorouracil, mercaptopurine, methotrexate, pemetrexed, pentostatin, pralatrexate, or thioguanine. In some aspects, the antimetabolite is pemetrexed. In some aspects, the taxane is paclitaxel, albumin-bound paclitaxel, docetaxel, or cabazitaxel. In some aspects, the vinca alkaloid is vinblastine, vincristine, vinorelbine, vindesine, vincaminol, vineridine, or vinburnine. In some aspects, the vinca alkaloid is vinorelbine or vinblastine. In some respects, the topoisomerase inhibitor is etoposide, mitoxantrone, doxorubicin, irinotecan, topotecan, or camptothecin. In some respects, the topoisomerase inhibitor is etoposide. In some respects, the topoisomerase inhibitor is irinotecan.

[0041] In some respects, PDCT comprises cisplatin or carboplatin in combination with gemcitabine, pemetrexed, paclitaxel, albumin-bound paclitaxel, docetaxel, vinorelbine, vinblastine, etoposide or irinotecan.

[0042] In some respects, PDCT comprises cisplatin or carboplatin in combination with paclitaxel or albumin-bound paclitaxel.

[0043] In some respects, PDCT comprises cisplatin or carboplatin in combination with pemetrexed.

[0044] In some respects, the method further comprises administering an additional therapeutic agent to the individual. In some respects, the additional therapeutic agent comprises an anticancer agent. In some respects, the anticancer agent comprises a tyrosine kinase inhibitor, an antiangiogenic agent, a checkpoint inhibitor, a checkpoint stimulator, a chemotherapeutic agent, an immunotherapeutic agent, a platinum agent, an alkylating agent, a taxane, a nucleoside analogue, an antimetabolite, an inhibitor of Petition 870260055013, dated 08 / 06 / 2026, page 17 / 490 12 / 189 topoisomerase, an anthracycline, a vinca alkaloid, or any combination thereof.

[0045] In some respects, tyrosine kinase inhibitor comprises afatinib, erlotinib, dacomitinib, gefitinib, osimertinib, alectinib, brigatinib, ceritinib, crizotinib, lorlatinib, entrectinib, dabrafenib, trametinib, vemurafenib, larotrectinib or any combination thereof.

[0046] In some respects, the antiangiogenic agent comprises an inhibitor of a vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR), platelet-derived growth factor (PDGF), PDGF receptor (PDGFR), angiopoietin (Ang), tyrosine kinase with Ig-like and EGF-like domain receptors (Tie), hepatocyte growth factor (HGF), tyrosine protein kinase Met (c-MET), C-type lectin family 14 member A (CLEC14A), multimerin 2 (MMRN2), shock protein 70-1A (HSP70-1A), an epidermal growth factor (EGF), EGF receptor (EGFR) or any combination thereof.

[0047] In some respects, the antiangiogenic agent comprises bevacizumab, ramucirumab, aflibercept, tanibirumab, olaratumab, nesvacumab, AMG780, MEDI3617, vanucizumab, rilotumumab, ficlatuzumab, TAK-701, onartuzumab, emibetuzumab or any combination thereof.

[0048] In some respects, the checkpoint inhibitor comprises a programmed death pathway-1 (PD-1) inhibitor, a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor, a T-cell immunoglobulin and ITIM domain inhibitor (TIGIT), a T-cell immunoglobulin and mucin-containing domain inhibitor-3 (TIM-3), a TIM-1 inhibitor, a TIM-4 inhibitor, a B7-H3 inhibitor, a B7-H4 inhibitor, a B and T-cell lymphocyte attenuator (BTLA) inhibitor, a VISTA Ig T-cell activation suppressor inhibitor Petition 870260055013, dated 08 / 06 / 2026, page 18 / 490 13 / 189 (VISTA), an indoleamine 2,3-dioxygenase (IDO) inhibitor, a nicotinamide adenine dinucleotide phosphate oxidase isoform 2 (NOX2) inhibitor, an immunoglobulin-like killer cell receptor inhibitor (KIR) inhibitor, an adenosine A2a receptor (A2aR) inhibitor, a transforming growth factor beta (TGF-β) inhibitor, a phosphoinositide 3-kinase (PI3K) inhibitor, a CD47 inhibitor, a CD48 inhibitor, a CD73 inhibitor, a CD113 inhibitor, a sialic acid-binding immunoglobulin-like lectin-7 (SIGLEC-7) inhibitor, a SIGLEC-9 inhibitor, a SIGLEC-15 inhibitor, a glucocorticoid-induced TNFR-related protein (GITR) inhibitor, a galectin-1 inhibitor, a galectin-9 inhibitor, a cell adhesion molecule-1 inhibitor related to carcinoembryonic antigen (CEACAM-1), an inhibitor of G protein-coupled receptor 56 (GPR56), a predominant inhibitor of glycoprotein A repeats (GARP),a 2B4 inhibitor, a programmed death homolog-1 inhibitor (PD1H), a leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) inhibitor, or any combination thereof.

[0049] In some respects, the checkpoint inhibitor comprises an inhibitor of the PD-1 pathway.

[0050] In some respects, the PD-1 pathway inhibitor is an anti-PD-1 antibody and / or an anti-PD-L1 antibody.

[0051] In some respects, the PD-1 pathway inhibitor is an anti-PD-1 antibody.

[0052] In some respects, the anti-PD-1 antibody is a full-length antibody.

[0053] In some respects, the anti-PD-1 antibody is a monoclonal, human, humanized, chimeric, or multispecific antibody. In some respects, the multispecific antibody is a DART, a DVD-Ig, or a bispecific antibody. Petition 870260055013, dated 08 / 06 / 2026, page 19 / 490 14 / 189

[0054] In some respects, the anti-PD-1 antibody is a fragment F(ab') 2, a Fab' fragment, a Fab fragment, an Fv fragment, an scFv fragment, a dsFv fragment, a dAb fragment, or a single linking polypeptide chain.

[0055] In some respects, the anti-PD-1 antibody is nivolumab, pembrolizumab, PDR001 (spartalizumab), MEDI-0680, TSR-042, cemiplimab, JS001, PF-06801591, BGB-A317, BI 754091, INCSHR1210, GLS-010, AM-001, STI-1110, AGEN2034, MGA012, BCD100, IBI308, SSI-361, or comprises an antigen-binding portion thereof.

[0056] In some respects, the anti-PD-1 antibody comprises CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence shown in SEQ ID No:13 and CDR1, CDR2 and CDR3 domains of the variable light chain region with the sequence shown in SEQ ID No:14.

[0057] In some respects, the anti-PD-1 antibody comprises: (a) a CDR1 variable region heavy chain comprising the sequence presented in SEQ ID No:15; (b) a CDR2 variable region heavy chain comprising the sequence presented in SEQ ID No:16; (c) a CDR3 variable region heavy chain comprising the sequence presented in SEQ ID No:17; (d) a CDR1 variable region light chain comprising the sequence presented in SEQ ID No:18; (e) a CDR2 variable region light chain comprising the sequence presented in SEQ ID No:19; and (f) a CDR3 variable region light chain comprising the sequence presented in SEQ ID No:20.

[0058] In some respects, the anti-PD-1 antibody comprises variable heavy and light chain regions comprising the sequences presented in SEQ ID Nos: 13 and 14, respectively.

[0059] In some respects, the anti-PD-1 antibody comprises Petition 870260055013, dated 08 / 06 / 2026, p. 20 / 490 15 / 189 heavy and light chains comprising the sequences as set out in SEQ ID Nos. 11 and 12, respectively.

[0060] In some respects, the PD-1 pathway inhibitor is a soluble PD-L2 polypeptide. In some respects, the soluble PD-L2 polypeptide is a fusion polypeptide. In some respects, the soluble PD-L2 polypeptide comprises a ligand-binding fragment of the PD-L2 extracellular domain. In some respects, the soluble PD-L2 polypeptide further comprises a half-life extension portion. In some respects, the half-life extension portion comprises an immunoglobulin constant region or a portion thereof, an immunoglobulin-binding polypeptide, immunoglobulin G (IgG), albumin-binding polypeptide (ABP), a PASylation portion, a HESylation portion, XTEN, a PEGuiylation portion, an Fc region, or any combination thereof. In some respects, the soluble PD-L2 polypeptide is AMP-224.

[0061] In some respects, the PD-1 pathway inhibitor is an anti-PD-L1 antibody.

[0062] In some respects, the anti-PD-L1 antibody is a full-length antibody.

[0063] In some respects, the anti-PD-L1 antibody is a monoclonal, human, humanized, chimeric, or multispecific antibody. In some respects, the multispecific antibody is a DART, a DVD-Ig, or a bispecific antibody.

[0064] In some respects, the anti-PD-L1 antibody is an F(ab')2 fragment, a Fab' fragment, a Fab fragment, an Fv fragment, an scFv fragment, a dsFv fragment, a dAb fragment, or a single chain of linking polypeptide.

[0065] In some respects, the anti-PD-L1 antibody is BMS936559, atezolizumab, durvalumab, avelumab, STI-1014, CX-072, KN035, LY3300054, BGB-A333, ICO 36, FAZ053, CK-301 or competent Petition 870260055013, dated 08 / 06 / 2026, page 21 / 490 16 / 189 ends one of its antigen-binding portions.

[0066] In some respects, the PD-1 pathway inhibitor is BMS-986189.

[0067] In some respects, the checkpoint inhibitor comprises a CTLA-4 inhibitor.

[0068] In some respects, the CTLA-4 inhibitor is an anti-CTLA-4 antibody.

[0069] In some respects, the anti-CTLA-4 antibody is a full-length antibody.

[0070] In some respects, the anti-CTLA-4 antibody is a monoclonal, human, humanized, chimeric, or multispecific antibody. In some respects, the multispecific antibody is a DART, a DVDIg, or a bispecific antibody.

[0071] In some respects, the anti-CTLA-4 antibody is an F(ab')2 fragment, a Fab' fragment, a Fab fragment, an Fv fragment, an scFv fragment, a dsFv fragment, a dAb fragment, or a single chain of linking polypeptide.

[0072] In some respects, the anti-CTLA-4 antibody is ipilimumab, tremelimumab, MK-1308, AGEN-1884 or comprises an antigen-binding moiety thereof.

[0073] In some respects, the checkpoint inhibitor is formulated for intravenous administration.

[0074] In some respects, the LAG-3 antagonist and the checkpoint inhibitor are formulated separately. In some respects, each checkpoint inhibitor is formulated separately when the checkpoint inhibitor comprises more than one checkpoint inhibitor. In some respects, the checkpoint inhibitor is administered before the LAG-3 antagonist. In some respects, the LAG-3 antagonist is administered before the checkpoint inhibitor.

[0075] In some respects, the LAG-3 antagonist and the checkpoint inhibitor are formulated together. In some respects, two or more Petition 870260055013, dated 08 / 06 / 2026, page 22 / 490 17 / 189 checkpoint inhibitors are formulated together when the checkpoint inhibitor comprises more than one checkpoint inhibitor.

[0076] In some respects, the LAG-3 antagonist and the checkpoint inhibitor are administered simultaneously.

[0077] In some respects, the checkpoint inhibitor is administered in a flat dose.

[0078] In some respects, the checkpoint inhibitor is administered at a dose of at least about 0.25 mg to about 2,000 mg, about 0.25 mg to about 1,600 mg, about 0.25 mg to about 1,200 mg, about 0.25 mg to about 800 mg, about 0.25 mg to about 400 mg, about 0.25 mg to about 100 mg, about 0.25 mg to about 50 mg, about 0.25 mg to about 40 mg, about 0.25 mg to about 30 mg, about 0.25 mg to about 20 mg, about 20 mg to about 2,000 mg, about 20 mg to about 1,600 mg, about 20 mg to about 1,200 mg, about 20 mg to about 800 mg, about 20 mg to about 400 mg, about 20 mg to about 100 mg, about 100 mg to about 2000 mg, about 100 mg to about 1800 mg, about 100 mg to about 1600 mg, about 100 mg to about 1400 mg, about 100 mg to about 1200 mg, about 100 mg to about 1000 mg, about 100 mg to about 800 mg, about 100 mg to about 600 mg, about 100 mg to about 400 mg,about 400 mg to about 2000 mg, about 400 mg to about 1800 mg, about 400 mg to about 1600 mg, about 400 mg to about 1400 mg, about 400 mg to about 1200 mg, or about 400 mg to about 1000 mg.

[0079] In some respects, the checkpoint inhibitor is administered at a dose of approximately 0.25 mg, approximately 0.5 mg, approximately 0.75 mg, approximately 1 mg, approximately 1.25 mg, approximately 1.5 mg, approximately 1.75 mg, approximately 2 mg, approximately 2.25 mg, approximately 2.5 mg, approximately 2.75 mg, approximately 3 mg, approximately 3.25 mg, approximately 3.5 mg, approximately 3.75 Petition 870260055013, dated 08 / 06 / 2026, page 23 / 490 18 / 189 mg, approximately 4 mg, approximately 4.25 mg, approximately 4.5 mg, approximately 4.75 mg, approximately 5 mg, approximately 5.25 mg, approximately 5.5 mg, approximately 5.75 mg, approximately 6 mg, approximately 6.25 mg, approximately 6.5 mg, approximately 6.75 mg, approximately 7 mg, approximately 7.25 mg, approximately 7.5 mg, approximately 7.75 mg, approximately 8 mg, approximately 8.25 mg, approximately 8.5 mg, approximately 8.75 mg, approximately 9 mg, approximately 9.25 mg, approximately 9.5 mg, approximately 9.75 mg, approximately 10 mg, approximately 20 mg, approximately 30 mg, approximately 40 mg, approximately 50 mg, approximately 60 mg, approximately 70 mg, approximately 80 mg, approximately 90 mg, approximately 100 mg, approximately 110 mg, approximately 120 mg, approximately 130 mg, approximately 140 mg, approximately 150 mg, approximately 160 mg, approximately 170 mg, approximately 180 mg, approximately 190 mg, approximately 200 mg, approximately 210 mg, approximately 220 mg, approximately 230 mg, approximately 240 mg, approximately 250 mg, approximately 260 mg, approximately 270 mg, approximately 280 mg, approximately 290 mg, approximately 300 mg, approximately 310 mg, approximately 320 mg, approximately 330 mg, approximately 340 mg, approximately 350 mgapproximately 360 mg, approximately 370 mg, approximately 380 mg, approximately 390 mg, approximately 400 mg, approximately 410 mg, approximately 420 mg, approximately 430 mg, approximately 440 mg, approximately 450 mg, approximately 460 mg, approximately 470 mg, approximately 480 mg, approximately 490 mg, approximately 500 mg, approximately 510 mg, approximately 520 mg, approximately 530 mg, approximately 540 mg, approximately 550 mg, approximately 560 mg, approximately 570 mg, approximately 580 mg, approximately 590 mg, approximately 600 mg, approximately 610 mg, approximately 620 mg, approximately 630 mg, approximately 640 mg, approximately 650 mg, approximately 660 mg, about 670 mg, about 680 mg, about 690 mg, about 700 mg, about 710 mg, about 720 mg, about 730 mg, about 740 mg, about 750 mg, about 760 mg, about 770 mg, about 780 mg, about 790 mg, about 800 mg, about 810 mg, about 820 mg, about 830 mg, about 840 mg, about 850 mg, about 860 mg, about 870 mg, about 880 mg, about 890 mg, about 900 mg, about 910 mg, about 920 Petition 870260055013, dated 08 / 06 / 2026, page 24 / 490 19 / 189 mg, about 930 mg, about 940 mg, about 950 mg, about 960 mg, about 970 mg, about 980 mg, about 990 mg, about 1000 mg, about 1040 mg, about 1080 mg, about 1100 mg, about 1140 mg, about 1180 mg, about 1200 mg, about 1240 mg, about 1280 mg, about 1300 mg, about 1340 mg, about 1380 mg, about 1400 mg, about 1440 mg, about 1480 mg, about 1500 mg, about 1540 mg, about 1580 mg, about 1600 mg, about 1640 mg, about 1680 mg, about 1700 mg, about 1740 mg, about 1780 mg, about 1800 mg, about 1840 mg, about 1880 mg, about 1900 mg, about 1940 mg, approximately 1980 mg, or approximately 2000 mg.

[0080] In some respects, the checkpoint inhibitor is administered as a weight-based dose.

[0081] In some aspects, the checkpoint inhibitor is administered at a dose of about 0.003 mg / kg to about 25 mg / kg, about 0.003 mg / kg to about 20 mg / kg, about 0.003 mg / kg to about 15 mg / kg, about 0.003 mg / kg to about 10 mg / kg, about 0.003 mg / kg to about 5 mg / kg, about 0.003 mg / kg to about 1 mg / kg, about 0.003 mg / kg to about 0.9 mg / kg, about 0.003 mg / kg to about 0.8 mg / kg, about 0.003 mg / kg to about 0.7 mg / kg, about 0.003 mg / kg to about 0.6 mg / kg, about 0.003 mg / kg to about from 0.5 mg / kg, about 0.003 mg / kg to about 0.4 mg / kg, about 0.003 mg / kg to about 0.3 mg / kg, about 0.003 mg / kg to about 0.2 mg / kg, about 0.003 mg / kg to about 0.1 mg / kg, about 0.1 mg / kg to about 25 mg / kg, about from 0.1 mg / kg to about 20 mg / kg, about 0.1 mg / kg to about 15 mg / kg, about 0.1 mg / kg to about 10 mg / kg, about 0.1 mg / kg to about 5 mg / kg, about 0.1 mg / kg to about 1 mg / kg, about 1 mg / kg to about 25 mg / kg,about 1 mg / kg to about 20 mg / kg, about 1 mg / kg to about 15 mg / kg, about 1 mg / kg to about 10 mg / kg, about 1 mg / kg to cer, Petition 870260055013, dated 08 / 06 / 2026, page 25 / 490 20 / 189 about 5 mg / kg, about 5 mg / kg to about 25 mg / kg, about 5 mg / kg to about 20 mg / kg, about 5 mg / kg to about 15 mg / kg, about 5 mg / kg to about 10 mg / kg, about 10 mg / kg to about 25 mg / kg, about 10 mg / kg to about 20 mg / kg, about 10 mg / kg to about 15 mg / kg, about 15 mg / kg to about 25 mg / kg, about 15 mg / kg to about 20 mg / kg, or about 20 mg / kg to about 25 mg / kg.

[0082] In some aspects, the checkpoint inhibitor is administered at a dose of approximately 0.003 mg / kg, approximately 0.004 mg / kg, approximately 0.005 mg / kg, approximately 0.006 mg / kg, approximately 0.007 mg / kg, approximately 0.008 mg / kg, approximately 0.009 mg / kg, approximately 0.01 mg / kg, approximately 0.02 mg / kg, approximately 0.03 mg / kg, approximately 0.04 mg / kg, approximately 0.05 mg / kg, approximately 0.06 mg / kg, approximately 0.07 mg / kg, approximately 0.08 mg / kg, approximately 0.09 mg / kg, approximately 0.1 mg / kg, approximately 0.2 mg / kg, approximately 0.3 mg / kg, approximately 0.4 mg / kg, approximately 0.5 mg / kg, about 0.6 mg / kg, about 0.7 mg / kg, about 0.8 mg / kg, about 0.9 mg / kg, about 1.0 mg / kg, about 2.0 mg / kg, about 3.0 mg / kg, about 4.0 mg / kg, about 5.0 mg / kg, about 6.0 mg / kg, about 7.0 mg / kg, about 8.0 mg / kg, about 9.0 mg / kg, about 10.0 mg / kg, about 11.0 mg / kg, about 12.0 mg / kg, about 13.0 mg / kg, about 14.0 mg / kg, about 15.0 mg / kg, about 16.0 mg / kg, about 17.0 mg / kg, about 18.0 mg / kg, about 19.0 mg / kg,approximately 20.0 mg / kg, approximately 21.0 mg / kg, approximately 22.0 mg / kg, approximately 23.0 mg / kg, approximately 24.0 mg / kg, or approximately 25.0 mg / kg.

[0083] In some respects, the dose is administered once every week, once every two weeks, once every three weeks, once every four weeks, once every five weeks, once every six weeks, once every seven weeks, once every eight weeks, once every nine weeks, once every ten weeks, once every eleven weeks, or once Petition 870260055013, dated 08 / 06 / 2026, p. 26 / 490 21 / 189 every twelve weeks.

[0084] The present invention is directed to a method of treating a human individual with lung cancer, the method comprising administering to the individual: (a) a dose of about 360 mg of an anti-LAG-3 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable region of the heavy chain with the sequence presented in SEQ ID No:3 and CDR1, CDR2 and CDR3 domains of the variable region of the light chain with the sequence presented in SEQ ID No:4 and (b) a dose of about 360 mg of an anti-PD-1 antibody comprising CDR1, CDR2 and CDR3 domains of the variable region of the heavy chain with the sequence presented in SEQ ID No:13 and CDR1, CDR2 and CDR3 domains of the variable region of the light chain with the sequence presented in SEQ ID No:14.

[0085] The present invention is directed to a method of treating a human individual with lung cancer, the method comprising administering to the individual: (a) a dose of about 720 mg of an anti-LAG-3 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable region of the heavy chain with the sequence presented in SEQ ID No:3 and CDR1, CDR2 and CDR3 domains of the variable region of the light chain with the sequence presented in SEQ ID No:4, (b) a dose of about 360 mg of an anti-PD-1 antibody comprising CDR1, CDR2 and CDR3 domains of the variable region of the heavy chain with the sequence presented in SEQ ID No:13 and CDR1, CDR2 and CDR3 domains of the variable region of the light chain with the sequence presented in SEQ ID No:14.

[0086] In some respects, the method is a first-line therapy.

[0087] In some respects, the method is a second-line therapy.

[0088] In some respects, the method is a third-generation therapy. Petition 870260055013, dated 08 / 06 / 2026, page 27 / 490 22 / 189 line.

[0089] In some respects, the individual has progressed in a previous therapy.

[0090] In some respects, lung cancer is unresectable, advanced, recurrent, and / or metastatic.

[0091] In some respects, the individual suffers from stage IV lung cancer.

[0092] In some respects, lung cancer is a small cell lung cancer.

[0093] In some respects, lung cancer is non-small cell lung cancer (NSCLC). In some respects, NSCLC has a squamous histology. In some respects, NSCLC has a non-squamous histology.

[0094] In some respects, the method further comprises the administration of a PDCT. In some respects, the PDCT comprises a platinum agent in combination with a nucleoside analogue, an antimetabolite, a taxane, a vinca alkaloid, or a topoisomerase inhibitor. In some respects, the platinum agent is cisplatin, carboplatin, oxaliplatin, satraplatin, picoplatin, nedaplatin, triplatin, lipoplatin, or phenantriplatin. In some respects, the platinum agent is cisplatin. In some respects, the platinum agent is carboplatin. In some respects, the nucleoside analogue is cytarabine, gemcitabine, lamivudine, entecavir, or telbivudine. In some respects, the nucleoside analogue is gemcitabine. In some respects, the antimetabolite is capecitabine, cladribine, clofarabine, cytarabine, floxuridine, fludarabine, fluorouracil, mercaptopurine, methotrexate, pemetrexed, pentostatin, pralatrexate, or thioguanine. In some respects, the antimetabolite is pemetrexed.In some respects, the taxane is paclitaxel, albumin-bound paclitaxel, docetaxel, or cabazitaxel. In some respects, the vinca alkaloid is vinblastine, vincristine, or vinor. Petition 870260055013, dated 08 / 06 / 2026, p. 28 / 490 23 / 189 relbine, vindesine, vincaminol, vineridine, or vinburnine. In some aspects, the vinca alkaloid is vinorelbine or vinblastine. In some aspects, the topoisomerase inhibitor is etoposide, mitoxantrone, doxorubicin, irinotecan, topotecan, or camptothecin. In some aspects, the topoisomerase inhibitor is etoposide. In some aspects, the topoisomerase inhibitor is irinotecan. In some aspects, PDCT comprises cisplatin or carboplatin in combination with gemcitabine, pemetrexed, paclitaxel, albumin-bound paclitaxel, docetaxel, vinorelbine, vinblastine, etoposide, or irinotecan. In some aspects, PDCT comprises cisplatin or carboplatin in combination with paclitaxel or albumin-bound paclitaxel. In some respects, PDCT comprises cisplatin or carboplatin in combination with pemetrexed.

[0095] The present invention is directed to a method of treating a human individual with Stage IV or recurrent NSCLC who has a squamous histology, the method comprising administering to the individual: (a) a dose of approximately 360 mg of an anti-LAG-3 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable region of the heavy chain with the sequence presented in SEQ ID No.:3 and the CDR1, CDR2 and CDR3 domains of the variable region of the light chain with the sequence presented in SEQ ID No.:4, (b) a dose of approximately 360 mg of an anti-PD-1 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable region of the heavy chain with the sequence presented in SEQ ID No.:13 and the CDR1, CDR2 and CDR3 domains of the variable region of the light chain with the sequence presented in SEQ ID No.:14, (c) a PDCT comprising: (i) a dose of carboplatin for an area (i) a target under the concentration-time curve of approximately 6 mg / mL^min, and (ii) a dose of approximately 200 mg / m2 of paclitaxel,where the method is a first-line therapy.

[0096] The present invention relates to a method of treatment Petition 870260055013, dated 08 / 06 / 2026, p. 29 / 490 24 / 189 of a human individual with Stage IV or recurrent NSCLC who has a squamous histology, the method comprising administering to the individual: (a) a dose of approximately 720 mg of an anti-LAG-3 antibody comprising the CDR1, CDR2, and CDR3 domains of the variable region of the heavy chain with the sequence presented in SEQ ID No. 3 and the CDR1, CDR2, and CDR3 domains of the variable region of the light chain with the sequence presented in SEQ ID No. 4, (b) a dose of approximately 360 mg of an anti-PD-1 antibody comprising CDR1, CDR2, and CDR3 domains of the variable region of the heavy chain with the sequence presented in SEQ ID No. 13 and CDR1, CDR2, and CDR3 domains of the variable region of the light chain with the sequence presented in SEQ ID No. 14, (c) a PDCT comprising: (i) a dose of carboplatin to a target area under the concentration-time curve of approximately (i) a dose of 6 mg / mL^min, and (ii) a dose of approximately 200 mg / m2 of paclitaxel, where the method is a first-line therapy.

[0097] The present invention is directed to a method of treating a human individual with Stage IV or recurrent NSCLC who has a squamous histology, the method comprising administering to the individual: (a) a dose of approximately 360 mg of an anti-LAG-3 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable region of the heavy chain with the sequence presented in SEQ ID No. 3 and the CDR1, CDR2 and CDR3 domains of the variable region of the light chain with the sequence presented in SEQ ID No. 4, (b) a dose of approximately 360 mg of an anti-PD-1 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable region of the heavy chain with the sequence presented in SEQ ID No. 13 and the CDR1, CDR2 and CDR3 domains of the variable region of the light chain with the sequence presented in SEQ ID No. 14, (c) a PDCT comprising: (i) a dose of carboplatin for an area (i) a target under the concentration-time curve of approximately 6 mg / mL^min, and (ii) a dose of approximately 100 mg / m2 of pa Petition 870260055013, dated 08 / 06 / 2026, p. 30 / 490 25 / 189 clitaxel bound to albumin, where the method is a first-line therapy.

[0098] The present invention is directed to a method of treating a human individual with Stage IV or recurrent NSCLC who has a squamous histology, the method comprising administering to the individual: (a) a dose of approximately 720 mg of an anti-LAG-3 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable region of the heavy chain with the sequence presented in SEQ ID No.:3 and the CDR1, CDR2 and CDR3 domains of the variable region of the light chain with the sequence presented in SEQ ID No.:4, (b) a dose of approximately 360 mg of an anti-PD-1 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable region of the heavy chain with the sequence presented in SEQ ID No.:13 and the CDR1, CDR2 and CDR3 domains of the variable region of the light chain with the sequence presented in SEQ ID No.:14, (c) a PDCT comprising: (i) a dose of carboplatin for an area (i) a target under the concentration-time curve of approximately 6 mg / mL^min, and (ii) a dose of approximately 100 mg / m2 of albumin-bound paclitaxel,where the method is a first-line therapy.

[0099] The present invention relates to a method of treating a human individual with Stage IV or recurrent NSCLC who has a non-squamous histology, the method comprising administering to the individual: (a) a dose of approximately 360 mg of an anti-LAG-3 antibody comprising CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No. 3 and CDR1, CDR2 and CDR3 domains of the variable light chain region with the sequence presented in SEQ ID No. 4, (b) a dose of approximately 360 mg of an anti-PD-1 antibody comprising CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No. 13 and CDR1, CDR2 and CDR3 domains of the variable light chain region with the sequence presented in SEQ ID No. 14. Petition 870260055013, dated 08 / 06 / 2026, page 31 / 490 26 / 189 CDR3 of the variable light chain region with the sequence presented in SEQ ID No: 14, (c) a PDCT comprising: (i) a dose of carboplatin to a target area under the concentration-time curve of about 5 mg / mL^min or about 6 mg / mL*min, and (ii) a dose of about 500 mg / m2 of pemetrexed, wherein the method is a first-line therapy.

[00100] The present invention is directed to a method of treating a human individual with Stage IV or recurrent NSCLC who has a non-squamous histology, the method comprising administering to the individual: (a) a dose of approximately 720 mg of an anti-LAG-3 antibody comprising CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No.:3 and CDR1, CDR2 and CDR3 domains of the variable light chain region with the sequence presented in SEQ ID No.:4, (b) a dose of approximately 360 mg of an anti-PD-1 antibody comprising CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No.:13 and CDR1, CDR2 and CDR3 domains of the variable light chain region with the sequence presented in SEQ ID No.:14, (c) a PDCT comprising: (i) a dose of carboplatin for a target area under the concentration-time curve of about 5 mg / mL^min or about 6 mg / mL^min, and (ii) a dose of about 500 mg / m2 of pemetrexed,where the method is a first-line therapy.

[00101] The present invention is directed to a method of treating a human individual with Stage IV or recurrent NSCLC who has a non-squamous histology, the method comprising administering to the individual: (a) a dose of approximately 360 mg of an anti-LAG-3 antibody comprising CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No:3 and CDR1, CDR2 and CDR3 domains of the variable heavy chain region Petition 870260055013, dated 08 / 06 / 2026, page 32 / 490 27 / 189 light with the sequence presented in SEQ ID No:4, (b) a dose of approximately 360 mg of an anti-PD-1 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable region of the heavy chain with the sequence presented in SEQ ID No:13 and CDR1, CDR2 and CDR3 domains of the variable region of the light chain with the sequence presented in SEQ ID No:14, (c) a PDCT comprising: (i) a dose of approximately 75 mg / m2 of cisplatin and (ii) a dose of approximately 500 mg / m2 of pemetrexed, wherein the method is a first-line therapy.

[00102] The present invention is directed to a method of treating a human individual with Stage IV or recurrent NSCLC who has a non-squamous histology, the method comprising administering to the individual: (a) a dose of approximately 720 mg of an anti-LAG-3 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No. 3 and the CDR1, CDR2 and CDR3 domains of the variable light chain region with the sequence presented in SEQ ID No. 4, (b) a dose of approximately 360 mg of an anti-PD-1 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No. 13 and the CDR1, CDR2 and CDR3 domains of the variable light chain region with the sequence presented in SEQ ID No. 14, (c) a PDCT comprising: (i) a dose of approximately 75 mg / m2 of cisplatin and (ii) a dose of approximately 500 mg / m2 of pemetrexed, wherein the method is a first-line therapy.

[00103] In some respects, lung cancer is recurrent after multimodal therapy for locally advanced lung cancer.

[00104] In some respects, the individual has not received prior systemic therapy for cancer, the individual has not received prior systemic therapy for lung cancer, or the individual has not Petition 870260055013, dated 08 / 06 / 2026, page 33 / 490 28 / 189 received prior systemic therapy for advanced or metastatic lung cancer.

[00105] In some respects, the individual is naive to previous immuno-oncological therapy, the individual is naive to previous immuno-oncological therapy for lung cancer, or lung cancer is naive to previous immuno-oncological therapy.

[00106] In some respects, one or more immune cells in the individual's tumor tissue express LAG-3. In some respects, at least about 1%, at least about 3%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or about 100% of the immune cells express LAG-3. In some respects, at least about 1% of the immune cells express LAG-3. In some respects, the immune cells are tumor-infiltrating lymphocytes. In some respects, tumor-infiltrating lymphocytes are CD8+ cells.

[00107] In some respects, one or more tumor cells in the individual's tumor tissue express PD-L1. In some respects, at least about 1%, at least about 3%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or about 100% of the tumor cells express PD-L1. In some respects, at least about 1% of the tumor cells express PD-L1. Petition 870260055013, dated 08 / 06 / 2026, page 34 / 490 29 / 189

[00108] In some respects, (a) the anti-LAG-3 antibody comprises a variable region heavy chain CDR1, CDR2 and CDR3 comprising the sequence presented in SEQ ID No:5, SEQ ID No:6 and SEQ ID No:7, respectively, and a variable region light chain CDR1, CDR2 and CDR3 comprising the sequence presented in SEQ ID No:8, SEQ ID No:9 and SEQ ID No:10, respectively, and (b) the anti-PD-1 antibody comprises a variable region heavy chain CDR1, CDR2 and CDR3 comprising the sequence presented in SEQ ID No:15, SEQ ID No:16 and SEQ ID No:17, respectively, and a variable region light chain CDR1, CDR2 and CDR3 comprising the sequence presented in SEQ ID No:18, SEQ ID No:19 and SEQ ID No:20, respectively.

[00109] In some respects, the anti-LAG-3 antibody comprises variable heavy and light chain regions comprising the sequences presented in SEQ ID Nos. 3 and 4, respectively, and the anti-PD-1 antibody comprises variable heavy and light chain regions comprising the sequences presented in SEQ ID Nos. 13 and 14, respectively.

[00110] In some respects, the anti-LAG-3 antibody and / or the anti-PD-1 antibody is a full-length antibody.

[00111] In some respects, the anti-LAG-3 antibody and / or anti-PD-1 antibody is a monoclonal, human, humanized, chimeric, or multispecific antibody. In some respects, the multispecific antibody is a DART, a DVD-Ig, or a bispecific antibody.

[00112] In some respects, the anti-LAG-3 antibody and / or anti-PD-1 antibody is an F(ab')2 fragment, a Fab' fragment, a Fab fragment, an Fv fragment, an scFv fragment, a dsFv fragment, a dAb fragment, or a single-chain binding polypeptide.

[00113] In some respects, the anti-LAG-3 antibody comprises heavy and light chains comprising the sequences shown. Petition 870260055013, dated 08 / 06 / 2026, p. 35 / 490 30 / 189 in SEQ ID Nos. 1 and 2, respectively, and the anti-PD-1 antibody comprises heavy and light chains comprising the sequences defined in SEQ ID Nos. 11 and 12, respectively.

[00114] In some respects, the anti-LAG-3 antibody comprises heavy and light chains comprising the sequences presented in SEQ ID Nos. 21 and 2, respectively, and the anti-PD-1 antibody comprises heavy and light chains comprising the sequences defined in SEQ ID Nos. 11 and 12, respectively.

[00115] In some respects, the method further comprises administering to the individual an additional therapeutic agent. In some respects, the additional therapeutic agent comprises an anticancer agent. In some respects, the anticancer agent comprises a tyrosine kinase inhibitor, an antiangiogenic agent, a checkpoint inhibitor, a checkpoint stimulator, a chemotherapeutic agent, an immunotherapeutic agent, a platinum agent, an alkylating agent, a taxane, a nucleoside analogue, an antimetabolite, a topoisomerase inhibitor, an anthracycline, a vinca alkaloid, or any combination thereof.

[00116] In some respects, the tyrosine kinase inhibitor is afatinib, erlotinib, dacomitinib, gefitinib, osimertinib, alectinib, brigatinib, ceritinib, crizotinib, lorlatinib, entrectinib, dabrafenib, trametinib, vemurafenib, larotrectinib, or any combination thereof.

[00117] In some respects, the antiangiogenic agent comprises an inhibitor of a vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR), platelet-derived growth factor (PDGF), PDGF receptor (PDGFR), angiopoietin (Ang), tyrosine kinase with Ig-like and EGF-like domain receptors (Tie), hepatocyte growth factor (HGF), tyrosine protein kinase Met (c-MET), C-type lectin family 14 member A Petition 870260055013, dated 08 / 06 / 2026, page 36 / 490 31 / 189 (CLEC14A), multimerin 2 (MMRN2), shock protein 70-1A (HSP70-1A), an epidermal growth factor (EGF), an EGF receptor (EGFR), or any combination thereof.

[00118] In some respects, the antiangiogenic agent comprises bevacizumab, ramucirumab, aflibercept, tanibirumab, olaratumab, nesvacumab, AMG780, MEDI3617, vanucizumab, rilotumumab, ficlatuzumab, TAK-701, onartuzumab, emibetuzumab or any combination thereof.

[00119] In some respects, the checkpoint inhibitor comprises a programmed death pathway-1 (PD-1) inhibitor, a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor, a T-cell immunoglobulin and ITIM domain inhibitor (TIGIT), a T-cell immunoglobulin and mucin-containing domain inhibitor-3 (TIM-3), a TIM-1 inhibitor, a TIM-4 inhibitor, a B7-H3 inhibitor, a B7-H4 inhibitor, a B and T-cell lymphocyte attenuator (BTLA) inhibitor, a VISTA T-cell activation suppressor (VISTA) inhibitor, an indoleamine 2,3-dioxygenase (IDO) inhibitor, a nicotinamide adenine dinucleotide phosphate oxidase isoform 2 (NOX2) inhibitor, an immunoglobulin-like killer cell receptor inhibitor (KIR) inhibitor, an adenosine A2a receptor (A2aR) inhibitor, a Transforming growth factor beta (TGF-β) inhibitor, a phosphoinositide 3-kinase (PI3K) inhibitor, a CD47 inhibitor, a CD48 inhibitor,a CD73 inhibitor, a CD113 inhibitor, a sialic acid-binding immunoglobulin-like lectin-7 (SIGLEC-7) inhibitor, a SIGLEC-9 inhibitor, a SIGLEC-15 inhibitor, a glucocorticoid-induced TNFR-related protein (GITR) inhibitor, a galectin-1 inhibitor, a galectin-9 inhibitor, a carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM-1) inhibitor, a G protein-coupled receptor 56 (GPR56) inhibitor, a predominant inhibitor of... (Repetition 870260055013, 08 / 06 / 2026, page 37 / 490) 32 / 189 glycoprotein A inhibitors (GARP), a 2B4 inhibitor, a programmed death homolog-1 inhibitor (PD1H), a leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) inhibitor, or any combination thereof.

[00120] In some respects, the PD-1 pathway inhibitor is an anti-PD-L1 antibody.

[00121] In some respects, the anti-PD-L1 antibody is a full-length antibody.

[00122] In some respects, the anti-PD-L1 antibody is a monoclonal, human, humanized, chimeric, or multispecific antibody. In some respects, the multispecific antibody is a DART, a DVD-Ig, or a bispecific antibody.

[00123] In some respects, the anti-PD-L1 antibody is an F(ab') 2 fragment, a Fab' fragment, a Fab fragment, an Fv fragment, an scFv fragment, a dsFv fragment, a dAb fragment, or a single chain of linking polypeptide.

[00124] In some respects, the anti-PD-L1 antibody is BMS936559, atezolizumab, durvalumab, avelumab, STI-1014, CX-072, KN035, LY3300054, BGB-A333, ICO 36, FAZ053, CK-301 or comprises an antigen-binding moiety thereof.

[00125] In some respects, the PD-1 pathway inhibitor is BMS-986189.

[00126] In some respects, the checkpoint inhibitor comprises a CTLA-4 inhibitor.

[00127] In some respects, the CTLA-4 inhibitor is an anti-CTLA-4 antibody.

[00128] In some respects, the anti-CTLA-4 antibody is a full-length antibody.

[00129] In some respects, the anti-CTLA-4 antibody is a monoclonal, human, humanized, chimeric, or multispecific antibody. In some respects, the multispecific antibody is a DART, a DVD Petition 870260055013, dated 08 / 06 / 2026, page 38 / 490 33 / 189 Ig, or bispecific antibody.

[00130] In some respects, the anti-CTLA-4 antibody is an F(ab')2 fragment, a Fab' fragment, a Fab fragment, an Fv fragment, an scFv fragment, a dsFv fragment, a dAb fragment, or a single chain of linking polypeptide.

[00131] In some respects, the anti-CTLA-4 antibody is ipilimumab, tremelimumab, MK-1308, AGEN-1884 or comprises an antigen-binding moiety thereof.

[00132] In some respects, the anti-LAG-3 antibody and the anti-PD-1 antibody are formulated for intravenous administration.

[00133] In some respects, the checkpoint inhibitor is formulated for intravenous administration.

[00134] In some respects, the anti-LAG-3 antibody and the anti-PD-1 antibody are formulated separately.

[00135] In some respects, the anti-LAG-3 antibody and the anti-PD-1 antibody are formulated together.

[00136] In some respects, the anti-PD-1 antibody is administered before the anti-LAG-3 antibody.

[00137] In some respects, the anti-LAG-3 antibody is administered before the anti-PD-1 antibody.

[00138] In some respects, the LAG-3 antibody and the antiPD-1 antibody are administered simultaneously.

[00139] In some aspects, anti-LAG-3 antibody and anti-PD-1 antibody are administered approximately once every three weeks. In some aspects, anti-LAG-3 antibody and anti-PD-1 antibody are administered on Day 1 of each three-week cycle. In some aspects, anti-LAG-3 antibody and anti-PD-1 antibody are administered intravenously from a single intravenous bag over approximately 30 minutes.

[00140] In some respects, PDCT is administered every three Petition 870260055013, dated 08 / 06 / 2026, p. 39 / 490 34 / 189 weeks. In some respects, PDCT is administered for up to approximately 4 cycles of three weeks.

[00141] The present invention relates to a pharmaceutical composition comprising (a) 360 mg of an anti-LAG-3 antibody and (b) 360 mg of an anti-PD-1 antibody.

[00142] The present invention relates to a pharmaceutical composition comprising (a) 720 mg of an anti-LAG-3 antibody and (b) 360 mg of an anti-PD-1 antibody.

[00143] In some respects, (a) the anti-LAG-3 antibody comprises the CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence shown in SEQ ID No:3 and the CDR1, CDR2 and CDR3 domains of the variable light chain region with the sequence shown in SEQ ID No:4, and (b) the anti-PD-1 antibody comprises the CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence shown in SEQ ID No:13, and the CDR1, CDR2 and CDR3 domains of the variable light chain region with the sequence shown in SEQ ID No:14.

[00144] In some respects, (a) the anti-LAG-3 antibody comprises a variable region heavy chain CDR1, CDR2 and CDR3 comprising the sequence presented in SEQ ID No:5, SEQ ID No:6 and SEQ ID No:7, respectively, and a variable region light chain CDR1, CDR2 and CDR3 comprising the sequence presented in SEQ ID No:8, SEQ ID No:9 and SEQ ID No:10, respectively, and (b) the anti-PD-1 antibody comprises a variable region heavy chain CDR1, CDR2 and CDR3 comprising the sequence presented in SEQ ID No:15, SEQ ID No:16 and SEQ ID No:17, respectively, and a variable region light chain CDR1, CDR2 and CDR3 comprising the sequence presented in SEQ ID No:18, SEQ ID No:19 and SEQ ID No:20, respectively.

[00145] In some respects, the anti-LAG-3 antibody comprises Petition 870260055013, dated 08 / 06 / 2026, page 40 / 490 35 / 189 variable heavy and light chain regions comprising the sequences presented in SEQ ID Nos. 3 and 4, respectively, and the anti-PD-1 antibody comprises variable heavy and light chain regions comprising the sequences presented in SEQ ID Nos. 13 and 14, respectively.

[00146] In some respects, the anti-LAG-3 antibody and / or the anti-PD-1 antibody is a full-length antibody.

[00147] In some respects, the anti-LAG-3 antibody and / or anti-PD-1 antibody is a monoclonal, human, humanized, chimeric, or multispecific antibody. In some respects, the multispecific antibody is a DART, a DVD-Ig, or a bispecific antibody.

[00148] In some respects, the anti-LAG-3 antibody and / or anti-PD-1 antibody is an F(ab')2 fragment, a Fab' fragment, a Fab fragment, an Fv fragment, an scFv fragment, a dsFv fragment, a dAb fragment, or a single-chain binding polypeptide.

[00149] In some respects, the anti-LAG-3 antibody comprises heavy and light chains comprising the sequences presented in SEQ ID Nos. 1 and 2, respectively, and the anti-PD-1 antibody comprises heavy and light chains comprising the sequences defined in SEQ ID Nos. 11 and 12, respectively.

[00150] In some respects, the anti-LAG-3 antibody comprises heavy and light chains comprising the sequences presented in SEQ ID Nos. 21 and 2, respectively, and the anti-PD-1 antibody comprises heavy and light chains comprising the sequences defined in SEQ ID Nos. 11 and 12, respectively.

[00151] The present invention relates to a kit for treating a human individual with lung cancer, comprising: (a) 360 mg of an anti-LAG-3 antibody; (b) 360 mg of an anti-PD-1 antibody; and (c) instructions for using the anti-LAG-3 antibody and the anti-PD-1 antibody in a method for treating a human individual with lung cancer. Petition 870260055013, dated 08 / 06 / 2026, page 41 / 490 36 / 189 hand.

[00152] The present invention relates to a kit for treating a human individual with lung cancer, comprising: (a) 720 mg of an anti-LAG-3 antibody; (b) 360 mg of an anti-PD-1 antibody; and (c) instructions for using the anti-LAG-3 antibody and the anti-PD-1 antibody in a method for treating a human individual with lung cancer. DETAILED DESCRIPTION OF THE INVENTION

[00153] The present invention provides a method of treating a human individual with lung cancer (e.g., non-small cell lung cancer (NSCLC)), the method comprising administering to the individual an LAG-3 antagonist (e.g., an anti-LAG-3 antibody). Some aspects of the present invention are directed to a method of treating a human individual with lung cancer, wherein the method is a first-, second-, or third-line therapy. Some aspects of the present invention are directed to a method of treating a human individual with stage IV or recurrent lung cancer. The present invention is also directed to methods of treating a human individual with lung cancer comprising an anticancer therapy and / or a therapeutic agent in combination with the LAG-3 antagonist, such as chemotherapy (e.g., platinum doublet chemotherapy) and / or a PD-1 pathway inhibitor (e.g., an anti-PD-1 antibody). I. Terms

[00154] In order to make the present invention more easily understood, certain terms are first defined. As used in this application, except as expressly provided herein, each of the following terms shall have the meaning set forth below. Additional definitions are set forth throughout the application. Petition 870260055013, dated 08 / 06 / 2026, p. 42 / 490 37 / 189

[00155] It should be noted that the term "a" or "an entity" refers to one or more of these entities; for example, a nucleotide sequence is understood as representing one or more nucleotide sequences. As such, the terms "a," "one or more," and "at least one" may be used interchangeably herein.

[00156] The term and / or, when used herein, should be considered as a specific description of each of the two specified features or components with or without the other. Thus, the term and / or when used in a phrase such as A and / or B in this document is intended to include A and B, A or B, A (alone) and B (alone). Similarly, the term and / or used in a phrase such as A, B and / or C is intended to cover each of the following: A, B and C; A, B or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone).

[00157] It is understood that whenever aspects are described in this document using language comprising, analogous aspects described in terms of consisting of and / or consisting essentially of are also provided.

[00158] The terms approximately or comprising essentially of refer to a value or composition that is within an acceptable error range for the particular value or composition as determined by one skilled in the art, which will depend in part on how the value or composition is measured or determined, i.e., the limitations of the measurement system. For example, approximately or comprising essentially of may mean within 1 or more than 1 standard deviation according to practice in the art. Alternatively, approximately or comprising essentially of may mean a range up to 10% or 20% (i.e., ±10% or ±20%). For example, approximately 3 mg may include any number between 2.7 mg and 3.3 mg. Petition 870260055013, dated 08 / 06 / 2026, page 43 / 490 38 / 189 (for 10%) or between 2.4 mg and 3.6 mg (for 20%). Furthermore, particularly with regard to biological systems or processes, the terms may mean up to an order of magnitude or up to 5 times a value. When particular values ​​or compositions are given in the application and claims, unless otherwise indicated, the meaning of approximately or comprising essentially of should be considered within an acceptable error range for that particular value or composition.

[00159] As described in this document, any concentration range, percentage range, ratio range or whole range should be understood as including the value of any whole number within the indicated range and, where appropriate, fractions (such as one tenth and one hundredth of a whole), unless otherwise indicated.

[00160] Unless otherwise defined, all technical and scientific terms used in this document have the same meaning as commonly understood by one skilled in the art to which this description relates. For example, the Concise Dictionary of Biomedicine and Molecular Biology, Juo, Pei-Show, 2nd ed., 2002, CRC Press; The Dictionary of Cell and Molecular Biology, 5th ed., 2013, Academic Press; and the Oxford Dictionary of Biochemistry and Molecular Biology, 2006, Oxford University Press, provide a specialist with a general dictionary of many of the terms used in this description.

[00161] Units, prefixes and symbols are indicated in their form accepted by the International System of Units (SI). Numerical ranges include the numbers that define the range.

[00162] The headings given here are not limitations of the various aspects of the description, which may be considered as a reference to the descriptive report as a whole. Consequently, the terms defined immediately below are defined more fully by reference to the descriptive report in its entirety. Petition 870260055013, dated 08 / 06 / 2026, page 44 / 490 39 / 189

[00163] An antagonist should include, without limitation, any molecule capable of blocking, reducing, or otherwise limiting an interaction or activity of a target molecule (e.g., LAG-3). In some respects, the antagonist is an antibody. In other respects, the antagonist comprises a small molecule. The terms antagonist and inhibitor are used interchangeably herein.

[00164] An antibody (Ab) must include, without limitation, a glycoprotein immunoglobulin that specifically binds to an antigen and comprises at least two heavy chains (H) and two light chains (L) linked by disulfide bridges. Each H chain includes a variable heavy chain region (hereinafter abbreviated as Vh) and a constant heavy chain region (hereinafter abbreviated as Ch). The constant heavy chain region comprises three constant domains, Chi, CH2, and CH3. Each light chain includes a variable light chain region (hereinafter abbreviated as Vl) and a constant light chain region (hereinafter abbreviated as Cl). The constant light chain region comprises one constant domain, Cl. The Vh and Vl regions may be further subdivided into regions of hypervariability, called complementarity-determining regions (CDRs), interspersed with regions that are more conserved, called structural regions (FRs).Each Vh and Vl comprises three CDRs and four FRs, arranged from the amino-terminal to the carboxy-terminal in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The variable regions of the heavy and light chains contain a binding domain that interacts with an antigen. The constant regions of antibodies can mediate the binding of immunoglobulin to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (C1q) of the classical complement system. A heavy chain may or may not have a C-terminal lysine. Unless otherwise specified herein, the amino acids in the variable regions are numbered. Petition 870260055013, dated 08 / 06 / 2026, page 45 / 490 40 / 189 of those using the Kabat numbering system and those in the specified regions are numbered using the EU system.

[00165] An immunoglobulin may be derived from any of the commonly known isotypes, including, but not limited to, IgA, secretory IgA, IgG, and IgM. The IgG subclasses are also well known to those skilled in the art and include, but are not limited to, human IgG1, IgG2, IgG3, and IgG4. Isotype refers to the class or subclass of antibodies (e.g., IgM or IgG1) that is encoded by genes in the heavy chain constant region. The term antibody includes, by way of example, naturally occurring and unnaturally occurring antibodies; monoclonal and polyclonal antibodies; chimeric and humanized antibodies; human or non-human antibodies; entirely synthetic antibodies; single-chain antibodies; monospecific antibodies; bispecific antibodies; and multispecific antibodies. A non-human antibody may be humanized by recombinant methods to reduce its immunogenicity in humans.Where not expressly stated, and unless the context indicates otherwise, the term antibody also includes an antigen-binding fragment or an antigen-binding portion of any of the aforementioned immunoglobulins and includes a monovalent and divalent fragment or portion, which retains the ability to bind specifically to the antigen bound by the entire immunoglobulin. Examples of an antigen-binding portion or antigen-binding fragment include: (1) a Fab fragment (papain cleavage fragment) or a similar monovalent fragment consisting of the V1, Vh, L and Chi domains; (2) an F(ab')2 fragment (pepsin cleavage fragment) or a similar bivalent fragment comprising two Fab fragments linked by a disulfide bridge in the region of the joint; (3) an Fd fragment consisting of the VH and CH1 domains; (4) an Fv fragment consisting of the V1 and Vh domains of a single arm; (5) a frag. Petition 870260055013, dated 08 / 06 / 2026, page 46 / 490 41 / 189 single-domain antibody (dAb) (Ward et al., (1989) Nature 341: 544-46), consisting of a Vh domain; (6) a bi-single-domain antibody consisting of two Vh domains linked by a joint (dual-affinity redirection antibodies (DARTs)); or (7) a dual variable-domain immunoglobulin. Furthermore, although the two domains of the Fv fragment, VL and VH, are encoded by separate genes, they can be joined, using recombinant methods, by a synthetic linker that allows them to be made as a single protein chain in which the Vl and Vh regions pair to form monovalent molecules (known as single-chain Fv (scFv); see, for example, Bird et al. (1988) Science 242: 423-426; and Huston et al. (1988) Proc. Natl. Acad. Sci. USA 85: 5879-5883).

[00166] An isolated antibody refers to an antibody that is substantially free of other antibodies with different antigenic specificities (e.g., an isolated antibody that specifically binds to LAG-3 is substantially free of antibodies that do not specifically bind to LAG-3). An isolated antibody that specifically binds to LAG-3 may, however, cross-react with other antigens, such as LAG-3 molecules from different species. Furthermore, an isolated antibody may be substantially free of other cellular material and / or chemicals.

[00167] The term monoclonal antibody (mAb) refers to a non-natural preparation of antibody molecules of unique molecular composition, that is, antibody molecules whose primary sequences are essentially identical and which exhibit a unique binding specificity and affinity for a given epitope. An mAb is an example of an isolated antibody. mAbs can be produced by hybridoma, recombinant, transgenic, or other techniques known to those skilled in the art. Petition 870260055013, dated 08 / 06 / 2026, p. 47 / 490 42 / 189

[00168] A human antibody (HuMAb) refers to an antibody possessing variable regions in which both the structure and the CDR regions are derived from human germline immunoglobulin sequences. Furthermore, if the antibody contains a constant region, the constant region is also derived from human germline immunoglobulin sequences. The human antibodies of the invention may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo). However, the term human antibody, as used herein, is not intended to include antibodies in which germline-derived CDR sequences from another mammalian species, such as a mouse, have been grafted onto human structural sequences.The terms human antibodies and fully human antibodies are used synonymously.

[00169] A humanized antibody refers to an antibody in which some, most, or all of the amino acids outside the CDR domains of a non-human antibody are replaced by corresponding amino acids derived from human immunoglobulin. In one aspect of a humanized form of an antibody, some, most, or all of the amino acids outside the CDR domains have been replaced by amino acids from human immunoglobulins, while some, most, or all of the amino acids within one or more CDR regions remain unchanged. Minor additions, deletions, insertions, substitutions, or modifications of amino acids are permitted, provided they do not override the antibody's ability to bind to a specific antigen. A humanized antibody retains antigenic specificity similar to that of the original antibody.

[00170] A chimeric antibody refers to an antibody in which Petition 870260055013, dated 08 / 06 / 2026, pp. 48 / 490 43 / 189 the variable regions are derived from one species and the constant regions are derived from another species, such as an antibody in which the variable regions are derived from a mouse antibody and the constant regions are derived from a human antibody.

[00171] An anti-antigen antibody refers to an antibody that binds specifically to an antigen. For example, an anti-LAG-3 antibody binds specifically to LAG-3.

[00172] LAG-3 refers to Lymphocyte Activating Gene 3. The term LAG-3 includes variants, isoforms, homologs, orthologs, and paralogs. For example, antibodies specific for a human LAG-3 protein may, in certain cases, cross-react with a LAG-3 protein from a species other than human. In other respects, antibodies specific for a human LAG-3 protein may be completely specific for the human LAG-3 protein and not exhibit species or other types of cross-reactivity, or they may cross-react with LAG-3 from certain other species, but not all other species (e.g., cross-react with monkey LAG-3, but not mouse LAG-3). The term human LAG-3 refers to the human LAG-3 sequence, such as the complete amino acid sequence of human LAG-3 with GenBank accession number NP_002277.The term mouse LAG-3 refers to the mouse LAG-3 sequence, as well as the complete amino acid sequence of mouse LAG-3 having GenBank accession number NP_032505. LAG-3 is also known in the art as, for example, CD223. The human LAG-3 sequence may differ from the human LAG-3 of GenBank accession number NP_002277 by having, for example, conserved mutations or mutations in non-conserved regions, and LAG-3 has substantially the same biological function as the human LAG-3 of GenBank Accession No. NP_002277. For example, a biological function of human LAG-3... Petition 870260055013, dated 08 / 06 / 2026, p. 49 / 490 44 / 189 is not having an epitope in the extracellular domain of LAG-3 that is specifically bound by an antibody of the present invention or a biological function of human LAG-3 is binding to MHC Class II molecules.

[00173] A particular human LAG-3 sequence will generally be at least about 90% identical in amino acid sequence to the human LAG-3 from GenBank Accession No. NP_002277 and contains amino acid residues that identify the amino acid sequence as human when compared to LAG-3 amino acid sequences from other species (e.g., murine). In certain cases, a human LAG-3 may be at least about 95%, or even at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical in amino acid sequence to the LAG-3 from GenBank Accession No. NP_002277. In certain respects, a human LAG-3 sequence will exhibit no more than 10 amino acid differences from the LAG-3 sequence from GenBank Accession No. NP_002277. In certain aspects, human LAG-3 may exhibit no more than 5, or even no more than 4, 3, 2, or 1 amino acid difference from the LAG-3 sequence of GenBank accession number NP_002277.

[00174] Programmed Death-1 (PD-1) refers to an immunoinhibitory receptor belonging to the CD28 family. PD-1 is predominantly expressed on previously activated T cells in vivo and binds to two ligands, PD-L1 and PD-L2. The term PD-1, when used in this document, includes human PD-1 (hPD-1), variants, isoforms and homologous species of hPD-1 and analogs with at least one epitope in common with hPD-1. The complete hPD-1 sequence can be found under GenBank accession number U64863. PD-1 and PD-1 receptor are used interchangeably herein.

[00175] Cytotoxic T-lymphocyte antigen 4 (CTLA-4) refers to Petition 870260055013, dated 08 / 06 / 2026, p. 50 / 490 45 / 189 is an immunoinhibitory receptor belonging to the CD28 family. CTLA-4 is expressed exclusively on T cells in vivo and binds to two ligands, CD80 and CD86 (also called B7-1 and B7-2, respectively). The term CTLA-4, when used herein, includes human CTLA-4 (hCTLA-4), variants, isoforms and homologous species of hCTLA-4, and analogs with at least one epitope in common with hCTLA-4. The complete sequence of hCTLA-4 can be found under GenBank accession number AAB59385.

[00176] Programmed Death Ligand-1 (PD-L1) is one of two cell surface glycoprotein ligands for PD-1 (the other being PD-L2) that negatively regulate T cell activation and cytokine secretion upon binding to PD-1. The term PD-L1 as used in this document includes human PD-L1 (hPD-L1), variants, isoforms and homologous species of hPD-L1 and analogs with at least one epitope in common with hPD-L1. The complete hPD-L1 sequence can be found under GenBank accession number Q9NZQ7.

[00177] Programmed Death Ligand-2 (PD-L2), when used in this document, includes human PD-L2 (hPD-L2), variants, isoforms and homologous species of hPD-L2 and analogs with at least one epitope in common with hPD-L2. The complete hPD-L2 sequence can be found under GenBank accession number Q9BQ51.

[00178] A patient, as used in this document, includes any patient suffering from lung cancer (e.g., NSCLC). The terms individual and patient are used interchangeably herein.

[00179] To administer refers to the physical introduction of a therapeutic agent to an individual (for example, a composition or formulation comprising the therapeutic agent), using any of the various methods and systems of administration known to the versatility of medicine. Petition 870260055013, dated 08 / 06 / 2026, page 51 / 490 46 / 189 of the technique. Examples of routes of administration include intravenous, intramuscular, subcutaneous, intraperitoneal, spinal, or other parenteral routes of administration, for example, by injection or infusion. The phrase parenteral administration, as used herein, means modes of administration other than enteral and topical administration, generally by injection, and includes, without limitation, intravenous, intramuscular, intra-arterial, intrathecal, intralymphatic, intralesional, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intra-articular, subcapsular, subarachnoid, intraspinal, epidural, and intrasternal injection and infusion, as well as in vivo electroporation. In some respects, the formulation is administered non-parenterally, in some respects, orally.Other non-parenteral routes include topical, epidermal or mucosal administration, for example, intranasal, vaginal, rectal, sublingual or topical. Administration may also be performed, for example, once, multiple times and / or for one or more prolonged periods.

[00180] Treatment or therapy of an individual refers to any type of intervention or process performed or the administration of an active agent to the individual with the aim of reversing, alleviating, improving, inhibiting, delaying the progression, development, severity or recurrence of a symptom, complication or condition, or biochemical indicators associated with a disease. The Response Evaluation Criteria in Solid Tumors (RECIST) are a measure of treatment effectiveness and are established rules that define when tumors respond, stabilize or progress during treatment. RECIST 1.1 is the current guideline for measuring solid tumors and definitions for objective assessment of change in tumor size for use in adult and pediatric cancer clinical trials.

[00181] When used here, effective treatment refers to tra Petition 870260055013, dated 08 / 06 / 2026, page 52 / 490 47 / 189 Treatment that produces a beneficial effect, for example, improvement of at least one symptom of a disease or disorder. A beneficial effect may take the form of an improvement from baseline, that is, an improvement from a measurement or observation made before the start of therapy according to the method. A beneficial effect may also take the form of halting, slowing, delaying, or stabilizing a deleterious progression of a solid tumor marker. Effective treatment may refer to the relief of at least one symptom of a solid tumor. Such effective treatment may, for example, reduce the patient's pain, reduce the size and / or number of lesions, reduce or prevent metastasis of a tumor, and / or slow tumor growth.

[00182] The term effective amount refers to an amount of an agent that provides the desired biological, therapeutic, and / or prophylactic result. This result may be reduction, improvement, palliation, diminution, delay, and / or relief of one or more of the signs, symptoms, or causes of a disease or any other desired alteration of a biological system. In reference to solid tumors, an effective amount includes an amount sufficient to cause a tumor to shrink and / or decrease the rate of tumor growth (such as suppressing tumor growth) or delay other unwanted cell proliferation. In some respects, an effective amount is an amount sufficient to prevent or delay tumor recurrence. An effective amount may be administered in one or more administrations.The effective amount of the drug or composition can: (i) reduce the number of cancer cells; (ii) reduce the size of the tumor; (iii) inhibit, slow down, delay to some extent and may stop the infiltration of cancer cells into peripheral organs; (iv) inhibit (i.e., slow down to some extent and may stop) tumor metastasis; (v) inhibit tumor growth; (vi) prevent or delay the occurrence and / or recurrence. Petition 870260055013, dated 08 / 06 / 2026, page 53 / 490 48 / 189 of the tumor; and / or (vii) alleviate to some extent one or more of the symptoms associated with cancer. In one example, an effective amount is the amount of anti-LAG-3 antibody alone or the amount of anti-LAG-3 antibody and the amount of an additional therapeutic agent (e.g., anti-PD-1 antibody), in combination, clinically proven to affect a significant decrease in cancer or slow the progression of cancer, such as an advanced solid tumor.

[00183] When used in this document, the terms fixed dose, flat dose, and flat fixed dose are used interchangeably and refer to a dose that is administered to a patient regardless of the patient's weight or body surface area (BSA). The fixed or flat dose is therefore not given as a mg / kg dose, but rather as an absolute quantity of the agent (e.g., an amount in μg or mg).

[00184] The use of the term fixed-dose combination in relation to a composition of the invention means that two or more different inhibitors as described herein (for example, an anti-LAG3 antibody and an anti-PD-1 antibody) in a single composition are present in the composition in particular (fixed) proportions to each other. In some respects, the fixed dose is based on the weight (e.g., mg) of the inhibitors. In certain respects, the fixed dose is based on the concentration (e.g., mg / ml) of the inhibitors.In some respects, the ratio is at least about 1:1, about 1:2, about 1:3, about 1:4, about 1:5, about 1:6, about 1:7, about 1:8, about 1:9, about 1:10, about 1:15, about 1:20, about 1:30, about 1:40, about 1:50, about 1:60, about 1:70, about 1:80, about 1:90, about 1:100, about 1:120, about 1:140, about 1:160, about 1:180, about 1:200, about 200:1, about 180:1, about 160:1, about 140:1, about 120:1, about 100:1, about 90:1, about 80:1, about 70:1, about 60:1. Petition 870260055013, dated 08 / 06 / 2026, page 54 / 490 49 / 189 approximately 50:1, approximately 40:1, approximately 30:1, approximately 20:1, approximately 15:1, approximately 10:1, approximately 9:1, approximately 8:1, approximately 7:1, approximately 6:1, approximately 5:1, approximately 4:1, approximately 3:1, or approximately 2:1 mg of the first inhibitor to mg of the second inhibitor. For example, a 2:1 ratio of a first inhibitor to a second inhibitor may mean that a vial could contain approximately 720 mg of the first inhibitor and 360 mg of the second inhibitor, or approximately 12 mg / ml of the first inhibitor and 6 mg / ml of the second inhibitor.

[00185] The term weight-based as referred to here means that a dose administered to a patient is calculated based on the patient's weight.

[00186] Dosage interval, when used in this document, means the amount of time that elapses between multiple doses of a formulation described in this document being administered to an individual. The dosage interval may therefore be indicated as intervals.

[00187] The term dosage frequency when used here refers to the frequency of administration of doses of a formulation described herein at a given time. Dosage frequency may be indicated as the number of doses over a given period of time, for example, once a week or once every two weeks, etc.

[00188] The terms approximately once a week, once a week, once every two weeks, or any other similar dosing interval terms, as used in this document, mean approximate number, and approximately once a week or once every week may include every seven days ± two days, i.e., every five days every nine days. The once-a-week dosing frequency, therefore, may be every five days, every six days, every seven days, every eight days, or every nine days. Petition 870260055013, dated 08 / 06 / 2026, p. 55 / 490 50 / 189 days. Once every three weeks may include every 21 days ± 3 days, i.e., every 25 days every 31 days. Similar approximations apply, for example, once every two weeks, once every four weeks, once every five weeks, once every six weeks, once every seven weeks, once every eight weeks, once every nine weeks, once every ten weeks, once every eleven weeks, and once every twelve weeks. In some respects, a dosing interval of once every six weeks or once every twelve weeks means that the first dose may be administered on any day in the first week, and then the next dose may be administered on any day in the sixth or twelfth week, respectively.In other respects, a dosing interval of once every six weeks or once every twelve weeks means that the first dose is administered on a specific day of the first week (e.g., Monday), and then the next dose is administered on the same day of the sixth or twelfth week (i.e., Monday), respectively.

[00189] An adverse event (AE), as used in this document, is any unfavorable and generally unintended or undesirable sign (including an abnormal laboratory finding), symptom, or illness associated with the use of a medical treatment. For example, an adverse event may be associated with activation of the immune system or expansion of immune system cells (e.g., T cells) in response to a treatment. A medical treatment may have one or more associated AEs, and each AE may have the same or different levels of severity.

[00190] The term tumor, when used herein, refers to any mass of tissue resulting from excessive cell growth or proliferation, whether benign (non-cancerous) or malignant (cancerous), including Petition 870260055013, dated 08 / 06 / 2026, page 56 / 490 51 / 189 of precancerous lesions.

[00191] The term biological sample, as used herein, refers to biological material isolated from an individual. The biological sample may contain any biological material suitable for analysis, for example, sequencing nucleic acids in the tumor (or circulating tumor cells) and identifying a genomic alteration in the sequenced nucleic acids. The biological sample may be any suitable biological tissue or fluid, such as, for example, tumor tissue, blood, blood plasma, and serum. The biological sample may be a test tissue sample (e.g., a tissue sample comprising tumor cells and inflammatory cells infiltrating the tumor). In one aspect, the sample is a biopsy of tumor tissue, for example, formalin-fixed, paraffin-embedded (FFPE) tumor tissue or fresh frozen tumor tissue or the like.In another aspect, the biological sample is a liquid biopsy that, in some respects, comprises one or more of the following: blood, serum, plasma, circulating tumor cells, exoRNA, ctDNA, and cfDNA.

[00192] By way of example, an anticancer agent promotes cancer regression in an individual. In preferred aspects, a therapeutically effective amount of the agent promotes cancer regression to the point of eliminating the cancer. Promoting cancer regression means that the administration of an effective amount of the anticancer agent, alone or in combination with another agent, results in a reduction in tumor growth or size, tumor necrosis, a decrease in the severity of at least one disease symptom, an increase in the frequency and duration of disease-free periods, or a prevention of disability or incapacity due to disease affliction. Furthermore, the terms effective and efficacy in relation to a treatment include both pharmacological efficacy and physiological safety. Pharmacological efficacy refers to the ability Petition 870260055013, dated 08 / 06 / 2026, page 57 / 490 52 / 189 of the agent to promote cancer regression in the patient. Physiological safety refers to the level of toxicity or other adverse physiological effects at the cellular, organ and / or organism level (adverse effects) resulting from the administration of the agent.

[00193] By way of example for the treatment of tumors, a therapeutically effective amount of an anticancer agent may inhibit cell or tumor growth by at least about 20%, at least about 40%, at least about 60%, or at least about 80% compared to untreated individuals. In other aspects of the description, tumor regression may be observed and continue for a period of at least about 20 days, more preferably at least about 40 days, or at least about 60 days. Despite these measures of therapeutic efficacy, the evaluation of immunotherapeutic drugs should also take into account response patterns related to the immune system.

[00194] When used in this document, an immuno-oncological therapy or an IO therapy or IO refers to a therapy that comprises the use of an immune response to target and treat a tumor in an individual. As such, when used in this document, an IO therapy is a type of anticancer therapy. In some respects, an IO therapy comprises the administration of an antibody to an individual. In some respects, an IO therapy comprises the administration to an individual of an immune cell, for example, a T cell, for example, a modified T cell, for example, a T cell modified to express a chimeric antigen receptor or a particular T cell receptor. In some respects, IO therapy comprises the administration of a therapeutic vaccine to an individual. In some respects, IO therapy comprises the administration of a cytokine or a chemokine to an individual. In some respects, IO therapy comprised the administration of an interleukin a Petition 870260055013, dated 08 / 06 / 2026, page 58 / 490 53 / 189 an individual. In some respects, IO therapy comprised the administration of an interferon to an individual. In some respects, IO therapy comprised the administration of a colony-stimulating factor to an individual.

[00195] An immune response refers to the action of a cell of the immune system (e.g., T lymphocytes, B lymphocytes, natural killer (NK) cells, macrophages, eosinophils, mast cells, dendritic cells, and neutrophils) and soluble macromolecules produced by any of these cells or the liver (including antibodies, cytokines, and complement) that results in selective targeting, binding, damage, destruction, and / or elimination from the body of a vertebrate of invading pathogens, pathogen-infected cells or tissues, cancerous or other abnormal cells, or, in cases of autoimmunity or pathological inflammation, normal human cells or tissues.

[00196] A tumor-infiltrating inflammatory cell or tumor-associated inflammatory cell is any type of cell that normally participates in an inflammatory response in an individual and that infiltrates tumor tissue. Such cells include tumor-infiltrating lymphocytes (TILs), macrophages, monocytes, eosinophils, histiocytes, and dendritic cells.

[00197] The term LAG-3 positive or LAG-3 positive expression, relating to LAG-3 expression, refers to tumor tissue (e.g., a test tissue sample) that is classified as expressing LAG-3 based on the proportion (i.e., percentage) of immune cells (e.g., tumor-infiltrating lymphocytes, such as CD8+ T cells) that express LAG-3 (e.g., greater than or equal to 1% expression).

[00198] LAG-3 negative or LAG-3 negative expression refers to tumor tissue (e.g., a test tissue sample) that is not classified as expressing LAG-3 (e.g., less than Petition 870260055013, dated 08 / 06 / 2026, page 59 / 490 54 / 189% expression of LAG-3).

[00199] The term PD-1 positive or PD-1 positive expression, relating to PD-1 expression, refers to tumor tissue (e.g., a test tissue sample) that is classified as expressing PD-1 based on the proportion (i.e., percentage) of immune cells (e.g., tumor-infiltrating lymphocytes, such as CD8+ T cells) that express PD-1 (e.g., greater than or equal to 1% expression).

[00200] PD-1 negative or PD-1 negative expression refers to tumor tissue (e.g., a test tissue sample) that is not classified as expressing PD-1 (e.g., less than 1% PD-1 expression).

[00201] The term PD-L1 positive or PD-L1 positive expression, relating to PD-L1 expression on the cell surface, refers to tumor tissue (e.g., a test tissue sample) that is scored as expressing PD-L1 based on the proportion (i.e., percentage) of tumor cells expressing PD-L1 (e.g., greater than or equal to 1% expression).

[00202] The term PD-L1 negative or PD-L1 negative expression refers to tumor tissue (e.g., a test tissue sample) that is not classified as expressing PD-L1 (e.g., less than 1% expression).

[00203] Several aspects of the invention are described in more detail in the following subsections. II. Dissemination Methods

[00204] Methods of treating a human individual with lung cancer are provided in this document, the methods comprising administering to the individual an LAG-3 antagonist (e.g., an anti-LAG-3 antibody) alone or in combination with one or more additional therapeutic agents (e.g., Petition 870260055013, dated 08 / 06 / 2026, page 60 / 490 55 / 189 an inhibitor of the PD-1 pathway, such as an anti-PD-1 antibody) and / or therapies (e.g., chemotherapy, such as platinum doublet chemotherapy).

[00205] In some respects, the method is a first-line therapy (1L).

[00206] In some respects, the method is a second-line therapy (2L).

[00207] In some respects, the method is a third-line therapy (3L).

[00208] In some respects, the individual has progressed on a previous therapy (e.g., a standard of care therapy). Standard treatment therapies for different types of cancer are well known to those skilled in the art. For example, the National Comprehensive Cancer Network (NCCN), an alliance of 21 major cancer centers in the U.S., publishes the NCCN Clinical Practice Guidelines in Oncology (NCCN GUIDELINES®) which provide detailed, up-to-date information on standard of care treatments for a wide variety of cancers. See NCCN GUIDELINES®, 2020, https: / / www.nccn.org / professionals / physician_gls / default.aspx, last accessed October 23, 2020.

[00209] In some respects, lung cancer is recurrent after multimodal therapy for locally advanced lung cancer.

[00210] In some respects, the individual has not received prior systemic therapy for cancer, the individual has not received prior systemic therapy for lung cancer, or the individual has not received prior systemic therapy for advanced or metastatic lung cancer.

[00211] In some respects, the individual is naive to prior immuno-oncological (IO) therapy. In some respects, the individual never received Petition 870260055013, dated 08 / 06 / 2026, page 61 / 490 56 / 189 beu IO therapy, received IO therapy for a cancer other than lung cancer, or received IO therapy for a previous lung cancer but not a current lung cancer. In some respects, the individual is naive to previous IO therapy, the individual is naive to previous IO therapy for lung cancer, or the lung cancer is naive to previous IO therapy. In some respects, the previous IO therapy is an antibody. In some respects, the antibody binds to a checkpoint inhibitor. In some respects, the previous IO therapy is an anti-PD-1 antibody and / or a combination of an anti-PD-1 antibody and an anti-CTLA-4 antibody.

[00212] In some respects, a method of the invention increases progression-free survival (PFS) duration, objective response rate (ORR), overall survival (OS), or any combination thereof compared with standard care therapy and / or a preceding therapy as disclosed herein.

[00213] In some respects, a method of the invention reduces the size of a tumor, inhibits the growth of a tumor, eliminates a tumor from the individual, prevents the recurrence of lung cancer, induces remission of lung cancer, provides a complete response or a partial response, or any combination thereof.

[00214] In some respects, the methods of the invention comprise administering to the individual an LAG-3 antagonist based on the individual's performance status and / or cancer stage. Performance status and / or cancer stage may be indicated by any one or more systems in the art.

[00215] In some respects, lung cancer is unresectable, advanced, recurrent, and / or metastatic.

[00216] In some respects, performance status is indicated by the Eastern Cooperative Oncology Group (ECOG PS) performance status, which uses standardized criteria to measure how the Petition 870260055013, dated 08 / 06 / 2026, page 62 / 490 57 / 189 Illness affects a patient's daily living abilities. Example definitions for ECOG PS include: 0 for a fully active patient capable of performing all pre-illness activities without restriction; 1 for a patient who is restricted in strenuous physical activity but ambulatory and capable of performing light or sedentary work; 2 for a patient who is ambulatory and capable of all self-care, awake and more than 50% of waking hours, but unable to perform any work activity; 3 for a patient who is capable only of limited self-care and is confined to a bed or chair for more than 50% of waking hours; and 4 for a completely incapacitated patient, unable to perform any self-care and totally confined to bed or chair.

[00217] In some aspects, the individual has an ECOG PS of 0, 1, 2, 3, or 4. In some aspects, the individual has an ECOG PS of < 3. In some aspects, the individual has an ECOG PS of < 2. In some aspects, the individual has an ECOG PS of < 1.

[00218] In some respects, lung cancer is staged based on a tumor / node / metastasis (TNM) staging system, such as the American Joint Committee on Cancer (AJCC) classification.

[00219] There are at least seven stages used for lung cancer: occult stage (hidden), stage 0 (carcinoma in situ), stage I, stage II, stage IIIA, stage IIIB, and stage IV. In the occult stage, the cancer cannot be seen by imaging or bronchoscopy. In stage 0, cancerous cells are found in the lining of the airways.

[00220] In some respects, the individual suffers from stage 0 lung cancer.

[00221] In some respects, the individual suffers from Stage I lung cancer. Stage I lung cancer is divided into stages Petition 870260055013, dated 08 / 06 / 2026, page 63 / 490 58 / 189 IA and IB. In stage IA, the tumor is only in the lung and is 3 centimeters or less. In stage IB, the cancer has not spread to the lymph nodes and one or more of the following is true: 1) The tumor is larger than 3 centimeters, but not larger than 5 centimeters; 2) The cancer has spread to the main bronchus and is at least 2 centimeters below where the trachea joins the bronchus; 3) the cancer has spread to the innermost layer of the membrane covering the lung; or 4) Part of the lung has collapsed or developed pneumonitis (inflammation of the lung) in the area where the trachea joins the bronchus.

[00222] In some respects, the individual suffers from stage II lung cancer. Stage II is divided into Stage IIA and IIB. In stage IIA, the cancer has either spread to the lymph nodes or it has not. If the cancer has spread to the lymph nodes, then the cancer can only have spread to the lymph nodes on the same side of the chest as the tumor, the lymph nodes with cancer are within the lung or near the bronchus, and one or more of the following is true: 1) The tumor is no larger than 5 centimeters; 2) The cancer has spread to the main bronchus and is at least 2 centimeters below where the trachea joins the bronchus; 3) the cancer has spread to the innermost layer of the membrane covering the lung; or 4) Part of the lung has collapsed or developed pneumonitis (inflammation of the lung) in the area where the trachea joins the bronchus. The tumor is also considered Stage IIA if the cancer has not spread to the lymph nodes and one or more of the following is present. Petition 870260055013, dated 08 / 06 / 2026, p. 64 / 490 59 / 189 true: 1) The tumor is larger than 5 centimeters, but not larger than 7 centimeters; 2) The cancer has spread to the main bronchus and is at least 2 centimeters below where the trachea joins the bronchus; 3) the cancer has spread to the innermost layer of the membrane covering the lung; or 4) Part of the lung has collapsed or developed pneumonitis (lung inflammation) in the area where the trachea joins the bronchus. In stage IIB, the cancer has either spread to the lymph nodes or not. If the cancer has spread to the lymph nodes, then the cancer can only have spread to the lymph nodes on the same side of the chest as the tumor, the lymph nodes with cancer are within the lung or near the bronchus, and one or more of the following is true: 1) The tumor is larger than 5 centimeters, but not larger than 7 centimeters; 2) The cancer has spread to the main bronchus and is at least 2 centimeters below where the trachea joins the bronchus; 3) the cancer has spread to the innermost layer of the membrane covering the lung; or 4) Part of the lung has collapsed or developed pneumonitis (inflammation of the lung) in the area where the trachea joins the bronchus. The tumor is also considered Stage IIB if the cancer has not spread to the lymph nodes and one or more of the following is true: 1) The tumor is larger than 7 centimeters; 2) the cancer has spread to the main bronchus (and is Petition 870260055013, dated 08 / 06 / 2026, page 65 / 490 60 / 189 (at least 2 centimeters below where the trachea joins the bronchus), the chest wall, the diaphragm, or the nerve that controls the diaphragm; 3) The cancer has spread to the membrane surrounding the heart or lining the chest wall; 4) the entire lung collapsed or developed pneumonitis (inflammation of the lung); or 5) There is one or more separate tumors in the same lobe of the lung.

[00223] In some respects, the individual suffers from stage III lung cancer. Stage IIIA is divided into 3 sections. These 3 sections are based on 1) the size of the tumor; 2) where the tumor is found; and 3) which (if any) lymph nodes have cancer. In the first type of stage IIIA, the cancer has spread to the lymph nodes on the same side of the chest as the tumor, and the lymph nodes with cancer are near the sternum or where the bronchus enters the lung.Additionally: 1) the tumor can be of any size; 2) part of the lung (where the trachea joins the bronchus) or the entire lung may have collapsed or developed pneumonitis (inflammation of the lung); 3) there may be one or more separate tumors in the same lobe of the lung; and 4) the cancer may have spread to any of the following: a) the main bronchus, but not the area where the trachea joins the bronchus, b) the chest cavity, c) the diaphragm and the nerve that controls it, d) the membrane around the lung or lining the chest wall, e) the membrane around the heart. In the second type, stage IIIA, the cancer has spread to the lymph nodes on the same side of the chest as the tumor, and the lymph nodes with cancer are within the lung or near the bronchus. Additionally: 1) The tumor can be of any size; 2) The entire lung may have collapsed or developed Petition 870260055013, dated 08 / 06 / 2026, p. 66 / 490 61 / 189 pneumonitis (lung inflammation); 3) There may be one or more separate tumors in any of the lobes of the cancerous lung; and 4) The cancer may have spread to any of the following: a) main bronchus, but not the area where the trachea joins the bronchus, b) thoracic cavity, c) diaphragm and the nerve that controls it, d) membrane around the lung or lining the chest wall, e) heart or the membrane around it, f) large blood vessels leading to or from the heart, g) trachea, h) esophagus, i) nerve that controls the larynx (vocal cords), j) sternum (breastbone) or spine, or k) carina (where the trachea joins the bronchi). In the third type of Stage IIIA, the cancer has not spread to the lymph nodes, the tumor can be of any size, and the cancer has spread to any of the following: a) heart, b) large blood vessels leading to or from the heart, c) trachea, d) esophagus, e) nerve that controls the larynx (voice box), f) sternum (breastbone) or spine, or g) carina (where the trachea joins the bronchi).Stage IIIB is divided into 2 sections, depending on 1) the size of the tumor, 2) where the tumor is found, and 3) which lymph nodes have cancer. In the first type of Stage IIIB, the cancer has spread to the lymph nodes on the opposite side of the chest as the tumor. Additionally, 1) the tumor can be of any size; 2) part of the lung (where the trachea joins the bronchus) or the entire lung may have collapsed or developed pneumonitis (inflammation of the lung); 3) there may be one or more separate tumors in any of the lung lobes with cancer; and 4) the cancer may have spread to any of the following: a) main bronchus, b) rib cage, c) diaphragm and the nerve that controls it, d) membrane around the lung or lining the chest wall, e) heart or the membrane around it, f) large blood vessels leading to or from it. Petition 870260055013, dated 08 / 06 / 2026, p. 67 / 490 62 / 189 the heart, g) trachea, h) esophagus, i) nerve that controls the larynx (voice box), j) sternum (breastbone) or spine, or k) carina (where the trachea joins the bronchi). In the second type, stage IIIB, the cancer has spread to the lymph nodes on the same side of the chest as the tumor. The lymph nodes with cancer are near the sternum (breastbone) or where the bronchus enters the lung. Additionally, 1) the tumor can be of any size; 2) there may be separate tumors in different lobes of the same lung; and 3) the cancer has spread to any of the following: a) heart, b) large blood vessels that enter or leave the heart, c) trachea, d) esophagus, e) nerve that controls the larynx (vocal cords), f) sternum (breastbone) or spine, or g) carina (where the trachea joins the bronchi).

[00224] In some respects, the individual has stage IV lung cancer. In stage IV, the tumor can be any size and the cancer may have spread to the lymph nodes. One or more of the following are true in Stage IV: 1) There is one or more tumors in both lungs; 2) the cancer is found in the fluid surrounding the lungs or heart; and 3) The cancer has spread to other parts of the body, such as the brain, liver, adrenal glands, kidneys, or bones.

[00225] In some respects, lung cancer is small cell lung cancer (SCLC). In some respects, SCLC staging is done by TNM staging. In some respects, instead of TNM staging, SCLC is staged as limited stage or extensive stage. Limited stage SCLC is confined to one lung and / or local lymph nodes. Extensive stage SCLC is found in both lungs and / or distant sites in the body. Petition 870260055013, dated 08 / 06 / 2026, page 68 / 490 63 / 189

[00226] In some respects, lung cancer is non-small cell lung cancer (NSCLC). NSCLC includes NSCLC with histology not otherwise specified (NOS), NSCLC with squamous histology (SQ), and NSCLC with non-squamous histology (NSQ, including adenocarcinoma, large cell, and undifferentiated carcinoma). In some respects, NSCLC has squamous histology. In some respects, NSCLC has non-squamous histology.

[00227] Surgery (i.e., surgical resection), radiotherapy (RT), and chemotherapy are three modalities commonly used to treat patients with NSCLC. As a class, NSCLCs are relatively insensitive to chemotherapy and RT compared to small cell carcinoma. In general, for patients with stage I or II disease, surgical resection offers the best chance of cure, with chemotherapy frequently used both pre- and post-operatively. RT may also be used as adjuvant therapy for patients with resectable NSCLC, primary local treatment, or as palliative therapy for patients with incurable NSCLC. Patients with advanced or metastatic disease (e.g., Stage IV NSCLC) who have a good performance status (PS) may benefit from chemotherapy.

[00228] Specific targeted therapies have also been developed for the treatment of advanced or metastatic NSCLC in individuals with sensitizing mutations in the genes for epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS-1, neurotrophin receptor tyrosine kinase (NTRK), and rapidly accelerating B-fibrosarcoma proto-oncogene (BRAF, e.g., the BRAF V600E mutation).

[00229] In some respects, the individual has an EGFR, ALK, NTRK, ROS-1, or BRAF mutation that is sensitive to therapy with targeted inhibitors. Petition 870260055013, dated 08 / 06 / 2026, page 69 / 490 64 / 189

[00230] In some respects, the individual does not have an EGFR, ALK, NTRK, ROS-1, or BRAF mutation that is sensitive to targeted inhibitor therapy.

[00231] In some respects, one or more immune cells in the individual's tumor tissue express LAG-3 (i.e., the patient's tumor tissue is LAG-3 positive) and / or one or more tumor cells in the individual's tumor tissue express PD-L1 (i.e., the patient's tumor tissue is PD-L1 positive). In some respects, one or more immune cells in the individual's tumor tissue express LAG-3. In some respects, at least about 1%, at least about 2%, at least about 3%, at least about 4%, at least about 5%, at least about 7%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or about 100% of immune cells express LAG-3.In some respects, at least about 1% of immune cells express LAG-3. In some respects, more than about 1% of immune cells express LAG-3. In some respects, at least about 5% of immune cells express LAG-3. In some respects, immune cells are tumor-infiltrating lymphocytes. In some respects, tumor-infiltrating lymphocytes are CD8+ cells. In some respects, one or more tumor cells in the individual's tumor tissue express PD-L1. In some respects, at least about 1%, at least about 2%, at least about 3%, at least about 4%, at least about 5%, at least about 7%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 40%. Petition 870260055013, dated 08 / 06 / 2026, page 70 / 490 65 / 189 in approximately 45%, at least approximately 50%, at least approximately 60%, at least approximately 70%, at least approximately 80%, at least approximately 90%, or approximately 100% of tumor cells express PD-L1. In some respects, at least approximately 1% of tumor cells express PD-L1. In some respects, at least approximately 1% of tumor cells express PD-L1. In some respects, more than approximately 1% of tumor cells express PD-L1. In some respects, at least approximately 5% of tumor cells express PD-L1. In some respects, any of the values ​​of at least approximately X% is >X%.

[00232] In some respects, one or more immune cells in the patient's tumor tissue do not express LAG-3 (that is, the patient's tumor tissue is LAG-3 negative). In some respects, tumor tissue is LAG-3 negative when less than about 1% of immune cells express LAG-3.

[00233] In some respects, one or more immune cells in the patient's tumor tissue do not express PD-1 (i.e., the patient's tumor tissue is PD-1 negative). In some respects, tumor tissue is PD-1 negative when less than about 1% of immune cells express PD-1.

[00234] In some respects, one or more tumor cells in the patient's tumor tissue do not express PD-L1 (that is, the patient's tumor tissue is PD-L1 negative). In some respects, tumor tissue is PD-L1 negative when less than about 1% of the tumor cells express PD-L1.

[00235] In some respects, the expression of LAG-3, PD-1, and / or PDL1 in an individual's tumor tissue is determined from a test tissue sample. In some respects, a test tissue sample includes, but is not limited to, any clinically relevant tissue sample, such as a tumor biopsy, a core biopsy, Petition 870260055013, dated 08 / 06 / 2026, page 71 / 490 66 / 189 an incisional biopsy, an excisional biopsy, a surgical specimen, a fine-needle aspirate, or a sample of body fluid such as blood, plasma, serum, lymph, ascitic fluid, cystic fluid, or urine. In some respects, the test tissue sample is from a primary tumor. In some respects, the test tissue sample is from a metastasis. In some respects, the test tissue samples are from various time points, for example, before treatment, during treatment, and / or after treatment. In some respects, the test tissue samples are from different locations in the individual, for example, from a primary tumor and from a metastasis.

[00236] In some respects, the test tissue sample is a paraffin-embedded, fixed tissue sample. In some respects, the test tissue sample is a formalin-fixed, paraffin-embedded (FFPE) tissue sample. In some respects, the test tissue sample is a fresh tissue sample (e.g., tumor). In some respects, the test tissue sample is a frozen tissue sample. In some respects, the test tissue sample is a fresh frozen (FF) tissue sample (e.g., tumor). In some respects, the test tissue sample is a cell isolated from a fluid. In some respects, the test tissue sample comprises circulating tumor cells (CTCs). In some respects, the test tissue sample comprises tumor-infiltrating lymphocytes (TILs). In some respects, the test tissue sample comprises both tumor cells and tumor-infiltrating lymphocytes (TILs).In some respects, the test tissue sample comprises circulating lymphocytes. In some respects, the test tissue sample is an archive tissue sample. In some respects, the test tissue sample is an archive tissue sample with a known history of diagnosis, treatment, and / or outcome. In some respects, the sample is a tissue block. In some respects, a. Petition 870260055013, dated 08 / 06 / 2026, page 72 / 490 67 / 189 test tissue sample is dispersed cells. In some respects, the sample size is from about 1 cell to about 1 x 10⁶ cells or more. In some respects, the sample size is from about 1 cell to about 1 x 10⁵ cells. In some respects, the sample size is from about 1 cell to about 10,000 cells. In some respects, the sample size is from about 1 cell to about 1,000 cells. In some respects, the sample size is from about 1 cell to about 100 cells. In some respects, the sample size is from about 1 cell to about 10 cells. In some respects, the sample size is a single cell.

[00237] In some aspects, the expression of LAG-3, PD-1 and / or PD-L1 is evaluated by performing an assay to detect the presence of LAG3, PD-1 and / or PD-L1 RNA, respectively. In some aspects, the presence of LAG-3, PD-1 and / or PD-L1 RNA is detected by RT-PCR, in situ hybridization or RNase protection.

[00238] In some aspects, the expression of LAG-3, PD-1 and / or PD-L1 is evaluated by performing an assay to detect the presence of the LAG-3, PD-1 and / or PD-L1 polypeptide, respectively. In some aspects, the presence of the LAG-3, PD-1 and / or PD-L1 polypeptide is detected by immunohistochemistry (IHC), enzyme-linked immunosorbent assay (ELISA), in vivo imaging or flow cytometry. II.A. LAG-3 Antagonists

[00239] A LAG-3 antagonist for use in the methods of the description includes, but is not limited to, LAG-3 binding agents and soluble LAG-3 polypeptides. LAG-3 binding agents include antibodies that bind specifically to LAG-3 (i.e., an anti-LAG-3 antibody). The term LAG-3 antagonist when used herein is interchangeable with the term LAG-3 inhibitor.

[00240] In some respects, the LAG-3 antagonist is an anti-LAG-3 antibody. Petition 870260055013, dated 08 / 06 / 2026, p. 73 / 490 68 / 189

[00241] Antibodies that bind to LAG-3 have been described, for example, in Int'l Publ. No. WO / 2015 / 042246 and US Publ. Nos. 2014 / 0093511 and 2011 / 0150892, each of which is incorporated herein by reference in its entirety.

[00242] An example of a useful LAG-3 antibody in the present invention is 25F7 (described in U.S. Publication No. 2011 / 0150892). An additional exemplary LAG-3 antibody useful in the present invention is BMS-986016 (relatlimab). In some respects, an anti-LAG-3 antibody useful in the present invention cross-competes with 25F7 or BMS-986016. In some respects, an anti-LAG-3 antibody useful in the present invention binds to the same epitope as 25F7 or BMS-986016. In some respects, an anti-LAG-3 antibody comprises six CDRs of 25F7 or BMS-986016.

[00243] Other anti-LAG-3 antibodies recognized in the art that can be used in the methods of the description include IMP731 (H5L7BW) described in US 2011 / 007023, MK-4280 (28G-10, favezelimab) described in WO2016028672 and North American Publication No. 2020 / 0055938, REGN3767 (fianlimab) described in Burova E, et al., J. Immunother. Cancer (2016); 4(Supp. 1): P195 and U.S. Patent No. 10,358,495, humanized BAP050 described in WO2017 / 019894, GSK2831781, IMP-701 (LAG525; ieramilimab) described in U.S. Patent No. 10,711,060 and Publ. 2020 / 0172617, aLAG3(0414), aLAG3(0416), Sym022, TSR-033, TSR075, XmAb22841 (previously AVA-017, AGEN1746, RO7247669, INCAGN02385, IBI-110, EMB-02, IBI-323, LBL-007, and ABL501. These and other anti-LAG-3 antibodies useful in the claimed invention can be found, for example: US 10,188,730, WO 2016 / 028672, WO 2017 / 106129, WO2017 / 062888, WO2009 / 044273, WO2018 / 069500, WO2016 / 126858, WO2014 / 179664, WO2016 / 200782, Petition 870260055013, dated 08 / 06 / 2026, page 74 / 490 69 / 189 WO2015 / 200119, WO2017 / 220555, WO2017 / 015560, WO2017 / 087901, WO2017 / 219995, WO2017 / 086419, WO2017 / 019846, WO2017 / 220569, WO2017 / 025498, WO2018 / 083087, US2017 / 0260271, WO2018 / 034227, WO2017 / 198741 WO2018 / 071500 WO2017 / 087589 WO2017 / 149143 WO2017 / 086367 WO2018 / 185046 WO2018 / 185043, WO2018 / 217940, WO19 / 011306, WO2018 / 208868, WO2014 / 140180, WO2018 / 201096, WO2018 / 204374 and WO2019 / 018730. The content of each of these references is incorporated by reference in its entirety.

[00244] The anti-LAG-3 antibodies that can be used in the methods described also include isolated antibodies that specifically bind to human LAG-3 and cross-compete for binding to human LAG-3 with any anti-LAG-3 antibody described herein, for example, relatlimab. In some respects, the anti-LAG-3 antibody binds to the same epitope as any of the anti-LAG-3 antibodies described herein, for example, relatlimab.

[00245] In some respects, antibodies that cross-compete for binding to human LAG-3 or bind to the same epitope region as any anti-LAG-3 antibody described herein, for example, relatlimab, are monoclonal antibodies. For administration to humans, these cross-competing antibodies are chimeric antibodies, modified antibodies, or humanized or human antibodies. Such chimeric, modified, humanized, or human monoclonal antibodies can be prepared and isolated by methods well known in the art.

[00246] The ability of antibodies to cross-compete for binding to an antigen indicates that antibodies bind to the same epitope region of the antigen and sterically prevent other cross-competing antibodies from binding to that epitope region. Petition 870260055013, dated 08 / 06 / 2026, p. 75 / 490 70 / 189 particular. These cross-competing antibodies are expected to have very similar functional properties to the reference antibody, for example, relatlimab, by virtue of their binding to the same epitope region. Cross-competing antibodies can be readily identified based on their cross-competing ability in standard binding assays such as Biacore analysis, ELISA assays or flow cytometry (see, for example, WO 2013 / 173223).

[00247] The anti-LAG-3 antibodies that can be used in the methods described also include antigen-binding portions of any of the complete antibodies above. It has been widely demonstrated that the antigen-binding function of an antibody can be performed by fragments of a complete antibody.

[00248] In some respects, the anti-LAG-3 antibody is a natural-sized antibody.

[00249] In some respects, the anti-LAG-3 antibody is a monoclonal, human, humanized, chimeric, or multispecific antibody. In some respects, the multispecific antibody is a dual-affinity redirecting antibody (DART), a DVD-Ig, or a bispecific antibody.

[00250] In some respects, the anti-LAG-3 antibody is an F(ab')2 fragment, a Fab' fragment, a Fab fragment, an Fv fragment, an scFv fragment, a dsFv fragment, a dAb fragment, or a single-chain binding polypeptide.

[00251] In some respects, the anti-LAG-3 antibody is BMS-986016 (relatlimab), IMP731 (H5L7BW), MK4280 (28G-10, favezelimab), REGN3767 (fianlimab), GSK2831781, humanized BAP050, IMP-701 (LAG525, ieramilimab), aLAG3(0414), aLAG3(0416), Sym022, TSR033, TSR-075, XmAb22841 (XmAb22841), MGD013 (tebotelimab), BI754111, FS118, P 13B02-30, AVA-017, 25F7, AGEN1746, Petition 870260055013, dated 08 / 06 / 2026, page 76 / 490 71 / 189 RO7247669, INCAGN02385, IBI-110, EMB-02, IBI-323, LBL-007, ABL501, or comprises its antigen-binding portion.

[00252] In some respects, the anti-LAG-3 antibody is relatlimab.

[00253] In some respects, the methods of the description comprise an anti-LAG-3 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No: 3 and the CDR1, CDR2 and CDR3 domains of the variable light chain region having the sequence presented in SEQ ID No: 4.

[00254] In some respects, the methods of the description comprise an anti-LAG-3 antibody comprising: (a) a CDR1 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 5; (b) a CDR2 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 6; (c) a CDR3 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 7; (d) a CDR1 of the variable light chain region comprising the sequence presented in SEQ ID No: 8; (e) a CDR2 of the variable light chain region comprising the sequence presented in SEQ ID No: 9; and (f) a CDR3 of the variable light chain region comprising the sequence presented in SEQ ID No: 10.

[00255] In some respects, the methods of the description comprise an anti-LAG-3 antibody comprising variable heavy and light chain regions comprising the sequences presented in SEQ ID Nos. 3 and 4, respectively.

[00256] In some respects, the methods of the description comprise an anti-LAG-3 antibody comprising heavy and light chains comprising the sequences presented in SEQ ID Nos. 1 and 2, respectively.

[00257] In some respects, the methods of description include Petition 870260055013, dated 08 / 06 / 2026, p. 77 / 490 72 / 189 dem an anti-LAG-3 antibody comprising heavy and light chains comprising the sequences shown in SEQ ID Nos. 21 and 2, respectively.

[00258] In some respects, the anti-LAG-3 antibody is MGD013 (tebotelimab), which is a bispecific PD-1 x LAG-3 DART. In some respects, tebotelimab is administered intravenously at a dose of approximately 300 mg or approximately 600 mg once every 2 or 3 weeks. In some respects, tebotelimab is administered intravenously at a dose of approximately 300 mg once every two weeks. In some respects, tebotelimab is administered intravenously at a dose of approximately 600 mg once every 3 weeks.

[00259] In some respects, the anti-LAG-3 antibody is REGN3767 (fianlimab). In some respects, fianlimab is administered intravenously at a dose of approximately 1 mg / kg, approximately 3 mg / kg, approximately 10 mg / kg, or approximately 20 mg / kg once every 3 weeks.

[00260] In some aspects, fianlimab is administered intravenously at a dose of approximately 1600 mg once every 3 weeks. In some aspects, the methods of the description comprise an anti-LAG-3 antibody comprising the CDR1, CDR2, and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No. 25 and the CDR1, CDR2, and CDR3 domains of the variable light chain region having the sequence presented in SEQ ID No. 26.

[00261] In some respects, the methods of the description comprise an anti-LAG-3 antibody comprising: (a) a CDR1 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 27; (b) a CDR2 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 28; (c) a CDR3 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 29; (d) a CDR4 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 29; (e) a CDR5 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 29; (f) a CDR6 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 29; (f) a CDR7 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 29; (f) a CDR8 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 29; (f) a CDR8 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 29; (f) a CDR9 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 29; (f) a CDR1 ...1 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 29; (f) a CDR1 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 29; (f) a CDR1 of the variable heavy chain region comprising the sequence presented in SEQ ID No: Petition 870260055013, dated 08 / 06 / 2026, page 78 / 490 73 / 189 sequence presented in SEQ ID No: 29; (d) a CDR1 of the variable light chain region comprising the sequence presented in SEQ ID No: 30; (e) a CDR2 of the variable light chain region comprising the sequence presented in SEQ ID No: 31; and (f) a CDR3 of the variable light chain region comprising the sequence presented in SEQ ID No: 32.

[00262] In some respects, the methods of the description comprise an anti-LAG-3 antibody comprising variable heavy and light chain regions comprising the sequences presented in SEQ ID Nos. 25 and 26, respectively.

[00263] In some respects, the methods of the description comprise an anti-LAG-3 antibody comprising heavy and light chains comprising the sequences presented in SEQ ID Nos. 23 and 24, respectively.

[00264] In some respects, the anti-LAG-3 antibody is LAG525 (ieramilimab). In some respects, ieramilimab is administered intravenously at a dose of approximately 300 mg, approximately 400 mg, approximately 500 mg, approximately 600 mg, approximately 700 mg, approximately 800 mg, approximately 900 mg, approximately 1000 mg, approximately 1100 mg, approximately 1200 mg, or approximately 1300 mg once every 2, 3, or 4 weeks.

[00265] In some respects, the methods of the description comprise an anti-LAG-3 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No: 47 and the CDR1, CDR2 and CDR3 domains of the variable light chain region having the sequence presented in SEQ ID No: 49.

[00266] In some respects, the methods of the description comprise an anti-LAG-3 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No: 48 and CDR1, CDR2 and CDR3 domains of Petition 870260055013, dated 08 / 06 / 2026, page 79 / 490 74 / 189 variable light chain region having the sequence presented in SEQ ID No: 50.

[00267] In some respects, the methods of the description comprise an anti-LAG-3 antibody comprising: (a) a CDR1 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 51; (b) a CDR2 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 52; (c) a CDR3 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 53; (d) a CDR1 of the variable light chain region comprising the sequence presented in SEQ ID No: 54; (e) a CDR2 of the variable light chain region comprising the sequence presented in SEQ ID No: 55; and (f) a CDR3 of the variable light chain region comprising the sequence presented in SEQ ID No: 56.

[00268] In some respects, the methods of the description comprise an anti-LAG-3 antibody comprising variable heavy and light chain regions comprising the sequences presented in SEQ ID Nos. 47 and 49, respectively.

[00269] In some respects, the methods of the description comprise an anti-LAG-3 antibody comprising variable heavy and light chain regions comprising the sequences presented in SEQ ID Nos. 48 and 50, respectively.

[00270] In some respects, the methods of the description comprise an anti-LAG-3 antibody comprising heavy and light chains comprising the sequences presented in SEQ ID Nos. 43 and 45, respectively.

[00271] In some respects, the methods of the description comprise an anti-LAG-3 antibody comprising heavy and light chains comprising the sequences presented in SEQ ID Nos. 44 and 46, respectively. Petition 870260055013, dated 08 / 06 / 2026, p. 80 / 490 75 / 189

[00272] In some aspects, the anti-LAG-3 antibody is MK4280 (favezelimab). In some aspects, favezelimab is administered intravenously at a dose of approximately 7 mg, approximately 21 mg, approximately 70 mg, approximately 210 mg, approximately 700 mg, or approximately 800 mg once every 3 weeks or once every 6 weeks. In some aspects, favezelimab is administered intravenously at a dose of approximately 200 mg once every 3 weeks. In some aspects, favezelimab is administered intravenously at a dose of approximately 800 mg once every 6 weeks. In some aspects, favezelimab is administered intravenously at a dose of approximately 800 mg on Day 1, then once every 3 weeks. In some aspects, favezelimab is administered for up to 35 cycles. In some respects, favezelimab is administered intravenously at a dose of approximately 800 mg over about 30 minutes on Day 1 of a three-week cycle for up to 35 cycles.

[00273] In some respects, the methods of the description comprise an anti-LAG-3 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No: 69 and the CDR1, CDR2 and CDR3 domains of the variable light chain region having the sequence presented in SEQ ID No: 70.

[00274] In some respects, the methods of the description comprise an anti-LAG-3 antibody comprising: (a) a CDR1 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 71; (b) a CDR2 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 72; (c) a CDR3 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 73; (d) a CDR1 of the variable light chain region comprising the sequence presented in SEQ ID No: 74; (e) a CDR2 of the variable light chain region comprising Petition 870260055013, dated 08 / 06 / 2026, page 81 / 490 76 / 189 ends the sequence presented in SEQ ID No: 75; and (f) a CDR3 of the variable light chain region comprising the sequence presented in SEQ ID No: 76.

[00275] In some respects, the methods of the description comprise an anti-LAG-3 antibody comprising variable heavy and light chain regions comprising the sequences presented in SEQ ID Nos: 69 and 70, respectively.

[00276] In some respects, the methods of the description comprise an anti-LAG-3 antibody comprising heavy and light chains comprising the sequences presented in SEQ ID Nos. 67 and 68, respectively.

[00277] In some respects, the LAG-3 antagonist is a soluble LAG-3 polypeptide. In some respects, the soluble LAG-3 polypeptide is a fusion polypeptide, for example, a fusion protein comprising the extracellular portion of LAG-3. In some respects, the soluble LAG-3 polypeptide is an LAG-3-Fc fusion polypeptide capable of binding to MHC Class II. In some respects, the soluble LAG-3 polypeptide comprises a ligand-binding fragment of the LAG-3 extracellular domain. In some respects, the ligand-binding fragment of the LAG-3 extracellular domain comprises an amino acid sequence with at least about 90%, at least about 95%, at least about 98%, at least about 99%, or about 100% sequence identity to SEQ ID No. 22. In some respects, the soluble LAG-3 polypeptide further comprises an extended half-life portion.In some respects, the half-life extension portion comprises a constant region of immunoglobulin or a portion thereof, an immunoglobulin-binding polypeptide, an immunoglobulin G (IgG), albumin-binding polypeptide (ABP), a PASylation portion, a HESylation portion, XTEN, a PEGuilation portion, a region. Petition 870260055013, dated 08 / 06 / 2026, page 82 / 490 77 / 189 Fc or any combination thereof. In some respects, the soluble LAG-3 polypeptide is IMP321 (eftilagimod alfa). See, for example, Brignone C, et al., J. Immunol. (2007); 179: 4202-4211 and WO2009 / 044273. In some respects, eftilagimod alfa is administered at a dose of approximately 30 mg. In some respects, eftilagimod alfa is administered subcutaneously at a dose of approximately 30 mg once every 2 weeks.

[00278] In some respects, an anti-LAG-3 antibody is used to determine LAG-3 expression. In some respects, an anti-LAG-3 antibody is selected for its ability to bind to LAG-3 in formalin-fixed paraffin-embedded (FFPE) tissue specimens. In some respects, an anti-LAG-3 antibody is able to bind to LAG-3 in frozen tissues. In some respects, an anti-LAG-3 antibody is able to distinguish between membrane-bound, cytoplasmic, and / or soluble forms of LAG-3.

[00279] In some respects, a useful anti-LAG-3 antibody for testing, detecting and / or quantifying LAG-3 expression according to the methods described herein is the mouse anti-LAG-3 monoclonal antibody IgG1 17B4. See, for example, Matsuzaki, J et al., PNAS (2010); 107: 7875.

[00280] In some respects, the LAG-3 antagonist is formulated for intravenous administration.

[00281] In some aspects, the anti-LAG-3 antibody is administered intravenously over approximately 30 minutes.

[00282] In some respects, the LAG-3 antagonist is administered at a fixed dose.

[00283] In some respects, the LAG-3 antagonist is administered at a dose of at least about 0.25 mg to about 2000 mg, about 0.25 mg to about 1600 mg, about 0.25 mg to about 1200 mg, about 0.25 mg to about 800 mg, about 0.25 mg to Petition 870260055013, dated 08 / 06 / 2026, p. 83 / 490 78 / 189 about 400 mg, about 0.25 mg to about 100 mg, about 0.25 mg to about 50 mg, about 0.25 mg to about 40 mg, about 0.25 mg to about 30 mg, about 0.25 mg to about 20 mg, about 20 mg to about 2000 mg, about 20 mg to about 1600 mg, about 20 mg to about 1200 mg, about 20 mg to about 800 mg, about 20 mg to about 400 mg, about 20 mg to about 100 mg, about 100 mg to about 2000 mg, about 100 mg to about 1800 mg, about 100 mg to about 1600 mg, about 100 mg to about 1400 mg, about 100 mg to about 1200 mg, about 100 mg to about 1000 mg, about 100 mg to about 800 mg, about 100 mg to about 600 mg, about 100 mg to about 400 mg, about 400 mg to about 2000 mg, about 400 mg to about 1800 mg, about 400 mg to about 1600 mg, about 400 mg to about 1400 mg, about 400 mg to about 1200 mg or about 400 mg to about 1000 mg.

[00284] In some aspects, the LAG-3 antagonist is administered at a dose of approximately 0.25 mg, approximately 0.5 mg, approximately 0.75 mg, approximately 1 mg, approximately 1.25 mg, approximately 1.5 mg, approximately 1.75 mg, approximately 2 mg, 2.25 mg, approximately 2.5 mg, approximately 2.75 mg, approximately 3 mg, approximately 3.25 mg, approximately 3.5 mg, approximately 3.75 mg, approximately 4 mg, approximately 4.25 mg, approximately 4.5 mg, approximately 4.75 mg, approximately 5 mg, approximately 5.25 mg, approximately 5.5 mg, approximately 5.75 mg, approximately 6 mg, approximately 6.25 mg, approximately 6.5 mg, approximately 6.75 mg, approximately 7 mg, approximately 7.25 mg, approximately 7.5 mg, approximately 7.75 mg, approximately 8 mg, approximately 8.25 mg, approximately 8.5 mg, approximately 8.75 mg, approximately 9 mg, approximately 9.25 mg, approximately 9.5 mg, approximately 9.75 mg, approximately 10 mg, approximately 20 mg, approximately 30 mg, approximately 40 mg, approximately 50 mg, approximately 60 mg, approximately 70 mg, approximately 80 mg, approximately 90 mg, approximately 100 mg, approximately 110 mg, approximately 120 mg, approximately 130 mg, approximately 140 mg, approximately 150 mg, approximately 160 mgabout, Petition 870260055013, dated 08 / 06 / 2026, p. 84 / 490 79 / 189 of 170 mg, approximately 180 mg, approximately 190 mg, approximately 200 mg, approximately 210 mg, approximately 220 mg, approximately 230 mg, approximately 240 mg, approximately 250 mg, approximately 260 mg, approximately 270 mg, approximately 280 mg, approximately 290 mg, approximately 300 mg, approximately 310 mg, approximately 320 mg, approximately 330 mg, approximately 340 mg, approximately 350 mg, approximately 360 mg, approximately 370 mg, approximately 380 mg, approximately 390 mg, approximately 400 mg, approximately 410 mg, approximately 420 mg, approximately 430 mg, approximately 440 mg, approximately 450 mg, approximately 460 mg, approximately 470 mg, approximately 480 mg, approximately 490 mg, approximately 500 mg, approximately 510 mg, approximately 520 mg, approximately 530 mg, approximately 540 mg, approximately 550 mg, approximately 560 mg, approximately 570 mg, approximately 580 mg, approximately 590 mg, approximately 600 mg, approximately 610 mg, approximately 620 mg, approximately 630 mg, approximately 640 mg, approximately 650 mg, approximately 660 mg, approximately 670 mg, approximately 680 mg, approximately 690 mg, approximately 700 mg, approximately 710 mg, approximately 720 mg, approximately 730 mg, approximately 740 mgapproximately 750 mg, approximately 760 mg, approximately 770 mg, approximately 780 mg, approximately 790 mg, approximately 800 mg, approximately 810 mg, approximately 820 mg, approximately 830 mg, approximately 840 mg, approximately 850 mg, approximately 860 mg, approximately 870 mg, approximately 880 mg, approximately 890 mg, approximately 900 mg, approximately 910 mg, approximately 920 mg, approximately 930 mg, approximately 940 mg, approximately 950 mg, approximately 960 mg, approximately 970 mg, approximately 980 mg, approximately 990 mg, approximately 1000 mg approximately 1040 mg, approximately 1080 mg, approximately 1140 mg, approximately 1180 mg, approximately 1200 mg, approximately 1280 mg, approximately 1300 mg, approximately 1380 mg, approximately 1400 mg, approximately 1440 mg, approximately 1500 mg, approximately 1540 mg, approximately 1600 mg, approximately 1640 mg, approximately 1680 mg, approximately 1740 mg, approximately 1780 mg, approximately 1840 mg, approximately 1880 mg, approximately 1900 mg, 1100 mg, approximately 1240 mg, 1340 mg, approximately 1480 mg, 1580 mg, approximately 1700 mg, 1800 mg, approximately 1940 mg, Petition 870260055013, dated 08 / 06 / 2026, p. 85 / 490 80 / 189 approximately 1980 mg or approximately 2000 mg.

[00285] In some respects, the LAG-3 antagonist is administered on a weight-based basis.

[00286] In some respects, the LAG-3 antagonist is administered at a dose from about 0.003 mg / kg to about 25 mg / kg, about 0.003 mg / kg to about 20 mg / kg, about 0.003 mg / kg to about 15 mg / kg, about 0.003 mg / kg to about 10 mg / kg, about 0.003 mg / kg to about 5 mg / kg, about 0.003 mg / kg to about 1 mg / kg, about 0.003 mg / kg to about 0.9 mg / kg, about 0.003 mg / kg to about 0.8 mg / kg, about 0.003 mg / kg to about 0.7 mg / kg, about 0.003 mg / kg to about 0.6 mg / kg, about 0.003 mg / kg to about 0.5 mg / kg, about 0.003 mg / kg to about 0.4 mg / kg, about 0.003 mg / kg to about 0.3 mg / kg, about 0.003 mg / kg to about 0.2 mg / kg, about 0.003 mg / kg to about 0.1 mg / kg, about 0.1 mg / kg to about 25 mg / kg, about 0.1 mg / kg to about 20 mg / kg, about 0.1 mg / kg to about 15 mg / kg, about 0.1 mg / kg to about 10 mg / kg, about 0.1 mg / kg to about 5 mg / kg, about 0.1 mg / kg to about 1 mg / kg, about 1 mg / kg to about 25 mg / kg,about 1 mg / kg to about 20 mg / kg, about 1 mg / kg to about 15 mg / kg, about 1 mg / kg to about 10 mg / kg, about 1 mg / kg to about 5 mg / kg, about 5 mg / kg to about 25 mg / kg, about 5 mg / kg to about 20 mg / kg, about 5 mg / kg to about 15 mg / kg, about 5 mg / kg to about 10 mg / kg, about 10 mg / kg to about 25 mg / kg, about 10 mg / kg to about 20 mg / kg, about 10 mg / kg to about 15 mg / kg, about 15 mg / kg to about 25 mg / kg, about 15 mg / kg to about 20 mg / kg or about 20 mg / kg to about 25 mg / kg.

[00287] In some respects, the LAG-3 antagonist is administered at a dose of approximately 0.003 mg / kg, approximately 0.004 mg / kg, approximately 0.005 mg / kg, approximately 0.006 mg / kg, approximately 0.007 mg / kg, approximately Petition 870260055013, dated 08 / 06 / 2026, page 86 / 490 81 / 189 of 0.008 mg / kg, about 0.009 mg / kg, about 0.01 mg / kg, about 0.02 mg / kg, approximately 0.03 mg / kg, approximately 0.04 mg / kg, approximately 0.05 mg / kg, approximately 0.06 mg / kg, approximately 0.07 mg / kg, approximately 0.08 mg / kg, approximately 0.09 mg / kg, approximately 0.1 mg / kg, approximately 0.2 mg / kg, approximately 0.3 mg / kg, approximately 0.4 mg / kg, approximately 0.5 mg / kg, approximately 0.6 mg / kg, approximately 0.7 mg / kg, approximately 0.8 mg / kg, approximately 0.9 mg / kg, approximately 1.0 mg / kg, approximately 2.0 mg / kg, approximately 3.0 mg / kg, approximately 4.0 mg / kg, approximately 5.0 mg / kg, approximately 6.0 mg / kg, approximately 7.0 mg / kg, about 8.0 mg / kg, about 9.0 mg / kg, about 10.0 mg / kg, mg / kg, mg / kg, mg / kg, mg / kg, about 11.0 mg / kg, about 12.0 mg / kg, about 13.0 about 14.0 mg / kg, about 15.0 mg / kg, about 16.0 about 17.0 mg / kg, about 18.0 mg / kg, about 19.0 about 20.0 mg / kg, about 21.0 mg / kg, about 22.0 about 23.0 mg / kg, about 24.0 mg / kg or about 25.0 mg / kg.

[00288] In some aspects, the dose is administered once every week, once every two weeks, once every three weeks, once every four weeks, once every five weeks, once every six weeks, once every seven weeks, once every eight weeks, once every nine weeks, once every ten weeks, once every eleven weeks, or once every twelve weeks.

[00289] In some respects, a LAG-3 antagonist as described herein is administered as monotherapy, i.e., the LAG-3 antagonist is not administered in combination with one or more additional therapeutic agents.

[00290] In some respects, a LAG-3 antagonist as described herein is administered as a combination therapy, i.e., the LAG-3 antagonist is administered in combination with one or more additional therapeutic agents and / or therapies. Petition 870260055013, dated 08 / 06 / 2026, p. 87 / 490 82 / 189 anticancer. II.B. Combined therapy

[00291] The additional therapeutic agent and / or anticancer therapy may comprise any known therapeutic agent or anticancer therapy, including a standard of care in the technique for the treatment of an individual suffering from lung cancer. In some respects, the LAG-3 antagonist is combined with a therapeutic agent and / or therapy described by the NCCN® Guidelines for the treatment of NSCLC. See, for example, therapeutic agents and therapies described in: https: / / www.cancertherapyadvisor.com / home / cancer-topics / lungcancer / lung-cancer-treatment-regimens-landing-page / non-small-celllung-cancer-treatment-regimens / , last accessed October 23, 2020. II.B.1. Anticancer therapies

[00292] In some respects, additional cancer therapy comprises surgery, radiotherapy, chemotherapy, immunotherapy, or any combination thereof. In some respects, additional cancer therapy comprises chemotherapy, including any chemotherapeutic agent disclosed herein. In some respects, chemotherapy comprises platinum-based doublet chemotherapy.

[00293] In some respects, PDCT comprises a platinum agent in combination with a nucleoside analogue, an antimetabolite, a taxane, a vinca alkaloid or a topoisomerase inhibitor.

[00294] In some respects, the platinum agent is cisplatin, carboplatin, oxaliplatin, satraplatin, picoplatin, nedaplatin, triplatin, lipoplatin, or phenantriplatin.

[00295] In some respects, the nucleoside analogue is cytarabine, gemcitabine, lamivudine, entecavir or telbivudine. In some respects, the nucleoside analogue is cytarabine, gemcitabine, lamivudine, entecavir or telbivudine. In some respects, the nucleoside analogue is cytarabine, gemcitabine, lamivudine, entecavir or telbivudine. Petition 870260055013, dated 08 / 06 / 2026, page 88 / 490 83 / 189 aspects, the nucleoside analogue is gemcitabine.

[00296] In some respects, the antimetabolite is capecitabine, cladribine, clofarabine, cytarabine, floxuridine, fludarabine, fluorouracil, mercaptopurine, methotrexate, pemetrexed, pentostatin, pralatrexate, or thioguanine. In some respects, the antimetabolite is pemetrexed.

[00297] In some respects, the taxane is paclitaxel, albumin-bound paclitaxel (also called nab-paclitaxel), docetaxel or cabazitaxel.

[00298] In some aspects, the vinca alkaloid is vinblastine, vincristine, vinorelbine, vindesine, vincaminol, vineridine, or vinburnine. In some aspects, the vinca alkaloid is vinorelbine or vinblastine.

[00299] In some respects, the topoisomerase inhibitor is etoposide, mitoxantrone, doxorubicin, irinotecan, topotecan, or camptothecin. In some respects, the topoisomerase inhibitor is etoposide. In some respects, the topoisomerase inhibitor is irinotecan.

[00300] In some aspects, PDCT is administered for about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about from 19, about 20, about 21, about 22, about 23 or about 24 weeks.

[00301] In some aspects, PDCT is administered every three weeks for approximately 1, approximately 2, approximately 3, approximately 4, approximately 5, approximately 6, approximately 7, or approximately 8 cycles. In some aspects, PDCT is administered every three weeks for approximately 1, approximately 2, approximately 3, approximately 4, approximately 5, or approximately 6 cycles. In some aspects, PDCT is administered every three weeks for approximately 1, approximately 2, approximately 3, or approximately 4 cycles.

[00302] In some cases, PDCT is administered for up to about 4, about 5, or about 6 three-week cycles. In some cases Petition 870260055013, dated 08 / 06 / 2026, p. 89 / 490 84 / 189 aspects, PDCT is administered for up to approximately 4 cycles of three weeks.

[00303] In some respects, the platinum agent is cisplatin. In some aspects, cisplatin is administered at a dose of about 25 mg / m2 to about 150 mg / m2, about 50 mg / m2 to about 100 mg / m2, about 75 mg / m2 to about 100 mg / m2, or about 75 mg / m2 to about 80 mg / m2. mg / m2, about 55 mg / m2, about 60 mg / m2, about 65 mg / m2, about 70 mg / m2, about 75 mg / m2, about 76 mg / m2, about 77 mg / m2, about 78 mg / m2, about 79 mg / m2, about 80 mg / m2, about 85 mg / m2, about 90 mg / m2, approximately 95 mg / m2, or approximately 100 mg / m2. In some cases, cisplatin is administered intravenously over approximately 60 minutes. In some cases, cisplatin is administered on Day 1 of a three-week cycle for up to approximately 4, 5, or 6 cycles.

[00304] In some respects, the platinum agent is carboplatin. In some respects, carboplatin is administered at a dose for a target area under the concentration-time curve (AUC) of about 1 mg / mL^min to about 10 mg / mL*min. In some respects, carboplatin is administered at a dose for a target AUC of about 1 mg / mL^min, about 2 mg / mL*min, about 3 mg / mL^min, about 4 mg / mL^min, about 5 mg / mL^min, about 6 mg / mL^min, about 7 mg / mL^min, about 8 mg / mL^min, about 9 mg / mL^min or about 10 mg / mL^min. In some respects, carboplatin is administered at a dose for a target AUC of about 2 mg / mL^min. In some respects, carboplatin is administered at a dose to achieve a target AUC of approximately 5 mg / mL·min. In some respects, carboplatin is administered at a dose to achieve a target AUC of approximately 6 mg / mL·min. In some respects, carboplatin is administered via... Petition 870260055013, dated 08 / 06 / 2026, p. 90 / 490 85 / 189 intravenously over approximately 30 minutes. In some cases, carboplatin is administered on Day 1 of a three-week cycle for up to approximately 4, 5, or 6 cycles.

[00305] The carboplatin dose can be calculated according to methods known in the art. In some respects, the carboplatin dose is calculated using Calvert's formula as follows: Carboplatin dose (mg) = target AUC χ (CrCl [mL / min] + 25). The calculation of creatine clearance (CrCl) in the Calvert formula can be determined using the Cockcroft-Gault formula: Cockcroft-Gault CrCl = [(140-age) x (Weight in kg) x (0.85 if female)] / (72 x Cr). The Cockcroft-Gault formula includes an individual's most recent weight (kg) and most recent serum creatinine (Cr) concentration (mg / dL). In some respects, if the calculation of CrCl using the Cockcroft-Gault formula yields a result > 125 mL / min, then CrCl is calculated using an alternative formula according to institutional standards or limited to 125 mL / min.

[00306] In some respects, PDCT comprises cisplatin or carboplatin in combination with gemcitabine, paclitaxel, albumin-bound paclitaxel, docetaxel, pemetrexed, vinorelbine, vinblastine, etoposide or irinotecan.

[00307] In some aspects, PDCT comprises cisplatin or carboplatin in combination with gemcitabine. In some aspects, gemcitabine is administered at a dose of approximately 1,000 mg / m2 to approximately 1,250 mg / m2. In some aspects, gemcitabine is administered at a dose of approximately 1,000 mg / m2, approximately 1,050 mg / m2, approximately 1,100 mg / m2, approximately 1,150 mg / m2, approximately 1,200 mg / m2, or approximately 1,250 mg / m2. In some aspects, gemcitabine is administered intravenously over approximately 30 minutes. In some aspects, gemcitabine is administered on days 1, 8, and 15 of a cycle of Petition 870260055013, dated 08 / 06 / 2026, page 91 / 490 86 / 189 three weeks for up to about 4, about 5, or about 6 cycles. In some aspects, gemcitabine is administered on days 1 and 8 of a three-week cycle for up to about 4, about 5, or about 6 cycles. In some aspects, PDCT comprises a dose of about 1,000 mg / m2 to about 1,250 mg / m2 of gemcitabine administered intravenously over about 30 minutes on days 1 and 8 of a three-week cycle for about 4 to about 6 cycles and a dose of about 75 mg / m2 to about 80 mg / m2 of cisplatin administered intravenously over about 60 minutes on Day 1 of each cycle. In some respects, PDCT comprises a dose of approximately 1,000 mg / m2 of gemcitabine administered intravenously over approximately 30 minutes on days 1, 8, and 15 of a three-week cycle for approximately 4 to 6 cycles, and carboplatin administered intravenously over approximately 30 minutes at a dose to a target AUC of approximately 5 mg / mL^min on Day 1 of each cycle.

[00308] In some respects, PDCT comprises cisplatin or carboplatin in combination with paclitaxel or albumin-bound paclitaxel.

[00309] In some respects, PDCT comprises cisplatin or carboplatin in combination with paclitaxel. In some aspects, paclitaxel is administered at a dose of about 45 mg / m2 to about 200 mg / m2. mg / m2, about 80 mg / m2, about 85 mg / m2, about 90 mg / m2, about 95 mg / m2, about 100 mg / m2, about 105 mg / m2, about 110 mg / m2, about 115 mg / m2, about 120 mg / m2, about 125 mg / m2, about 130 mg / m2, about 135 mg / m2, about 140 mg / m2, about 145 mg / m2, about 150 mg / m2, about 155 mg / m2, about 160 mg / m2, about 165 mg / m2, about 170 mg / m2, Petition 870260055013, dated 08 / 06 / 2026, page 92 / 490 87 / 189 approximately 175 mg / m2, approximately 180 mg / m2, approximately 185 mg / m2, approximately 190 mg / m2, approximately 195 mg / m2 or approximately 200 mg / m2. In some aspects, paclitaxel is administered intravenously over approximately 60 minutes to approximately 180 minutes. In some aspects, PDCT comprises a dose of approximately 200 mg / m2 of paclitaxel administered intravenously over approximately 180 minutes on Day 1 of a three-week cycle for approximately 4 to approximately 6 cycles and a dose of approximately 75 mg / m2 to approximately 80 mg / m2 of cisplatin administered intravenously over approximately 60 minutes on Day 1 of each cycle. In some respects, PDCT comprises a dose of approximately 135 mg / m2 of paclitaxel administered intravenously over approximately 180 minutes on Day 1 of a three-week cycle for approximately 4 to 6 cycles and a dose of approximately 75 mg / m2 of cisplatin administered intravenously over approximately 60 minutes on Day 1 of each cycle.In some aspects, PDCT comprises a dose of approximately 200 mg / m2 of paclitaxel administered intravenously over approximately 180 minutes on Day 1 of a three-week cycle for approximately 4 to 6 cycles and carboplatin administered intravenously over approximately 30 minutes at a dose to a target AUC of approximately 6 mg / mL^min on Day 1 of each cycle. In some aspects, PDCT comprises a dose of approximately 45 mg / m2 to approximately 50 mg / m2 of paclitaxel administered intravenously over approximately 60 minutes on Day 1 of a one-week cycle for approximately 7 cycles and carboplatin administered intravenously over approximately 30 minutes at a dose to a target AUC of approximately 2 mg / mL*min on Day 1 of each cycle.

[00310] In some respects, PDCT comprises cisplatin or carboplatin in combination with albumin-bound paclitaxel. In some respects, albumin-bound paclitaxel is administered at a dose of approximately 100 mg / m2. In some respects, albumin-bound paclitaxel Petition 870260055013, dated 08 / 06 / 2026, p. 93 / 490 88 / 189 albumin is administered intravenously over approximately 30 minutes. In some respects, PDCT comprises a dose of approximately 100 mg / m2 of albumin-bound paclitaxel administered intravenously over approximately 30 minutes on Days 1, 8, and 15 of a three-week cycle for approximately 4 cycles and a dose of approximately 75 mg / m2 to approximately 80 mg / m2 of cisplatin administered intravenously over approximately 60 minutes on Day 1 of each cycle. In some respects, PDCT comprises a dose of approximately 100 mg / m2 of albumin-bound paclitaxel administered intravenously over approximately 30 minutes on days 1, 8, and 15 of a three-week cycle for approximately 4 to 6 cycles, and carboplatin administered intravenously over approximately 30 minutes at a dose to a target AUC of approximately 6 mg / mL^min on Day 1 of each cycle.

[00311] In some aspects, PDCT comprises cisplatin or carboplatin in combination with docetaxel. In some aspects, docetaxel is administered at a dose of approximately 75 mg / m2. In some aspects, docetaxel is administered intravenously over approximately 60 minutes. In some aspects, PDCT comprises a dose of approximately 75 mg / m2 of docetaxel administered intravenously over approximately 60 minutes on Day 1 of a three-week cycle for approximately 4 to approximately 6 cycles and a dose of approximately 75 mg / m2 of cisplatin administered intravenously over approximately 60 minutes on Day 1 of each cycle. In some respects, PDCT comprises a dose of approximately 75 mg / m2 of docetaxel administered intravenously over approximately 60 minutes on Day 1 of a three-week cycle for approximately 4 to 6 cycles, and carboplatin administered intravenously over approximately 30 minutes at a dose to a target AUC of approximately 6 mg / mL^min on Day 1 of each cycle.

[00312] In some respects, PDCT comprises cisplatin or carboplatin in combination with pemetrexed. In some respects, Petition 870260055013, dated 08 / 06 / 2026, page 94 / 490 89 / 189 Pemetrexed is administered at a dose of approximately 500 mg / m2. In some aspects, pemetrexed is administered intravenously over approximately 10 minutes. In some aspects, PDCT comprises a dose of approximately 500 mg / m2 of pemetrexed administered intravenously over approximately 10 minutes on Day 1 of a three-week cycle for approximately 4 to approximately 6 cycles and a dose of approximately 75 mg / m2 of cisplatin administered intravenously over approximately 60 minutes on Day 1 of each cycle. In some aspects, PDCT comprises a dose of approximately 500 mg / m2 of pemetrexed administered intravenously over approximately 10 minutes on Day 1 of a three-week cycle for approximately 3 cycles and a dose of approximately 75 mg / m2 of cisplatin administered intravenously over approximately 60 minutes on Day 1 of each cycle.In some respects, PDCT comprises a dose of approximately 500 mg / m² of pemetrexed administered intravenously over approximately 60 minutes on Day 1 of a three-week cycle for approximately 4 to approximately 6 cycles and carboplatin administered intravenously over approximately 30 minutes at a dose to a target AUC of approximately 6 mg / mL·min on Day 1 of each cycle. In some respects, PDCT comprises a dose of approximately 500 mg / m² of pemetrexed administered intravenously over approximately 60 minutes on Day 1 of a three-week cycle for approximately 4 to approximately 6 cycles and carboplatin administered intravenously over approximately 30 minutes at a dose to a target AUC of approximately 5 mg / mL·min on Day 1 of each cycle.

[00313] In some aspects, PDCT comprises cisplatin or carboplatin in combination with etoposide. In some aspects, etoposide is administered at a dose of approximately 50 mg / m2 to approximately 100 mg / m2. In some aspects, etoposide is administered intravenously over approximately 30 minutes to approximately 60 minutes. In some aspects, PDCT comprises a dose of approximately 100 Petition 870260055013, dated 08 / 06 / 2026, p. 95 / 490 90 / 189 mg / m2 of etoposide administered intravenously over approximately 60 minutes on Days 1-3 of a three-week cycle for approximately 4 to 6 cycles, and a dose of approximately 100 mg / m2 of cisplatin administered intravenously over approximately 60 minutes on Day 1 of each cycle. In some respects, PDCT comprises a dose of approximately 100 mg / m2 of etoposide administered intravenously over approximately 60 minutes on Days 1-3 of a four-week cycle for approximately 4 cycles, and a dose of approximately 100 mg / m2 of cisplatin administered intravenously over approximately 60 minutes on Day 1 of each cycle. In some respects, PDCT comprises a dose of approximately 50 mg / m2 of etoposide administered intravenously over approximately 60 minutes on days 1-5 of a four-week cycle for approximately 2 cycles and a dose of approximately 50 mg / m2 of decisplatin (Na) administered intravenously over approximately 60 minutes on days 1 and 8 of each cycle.In some respects, PDCT comprises a dose of approximately 100 mg / m2 of etoposide administered intravenously over approximately 30 minutes on Days 1-3 of a three-week cycle for approximately 4 to approximately 6 cycles and carboplatin administered intravenously over approximately 30 minutes at a dose to a target AUC of approximately 5 mg / mL^min on Day 1 of each cycle.

[00314] In some aspects, PDCT comprises cisplatin and vinorelbine. In some aspects, vinorelbine is administered at a dose of about 25 mg / m2 to about 30 mg / m2. In some aspects, vinorelbine is administered intravenously over about 5 to about 10 minutes. In some aspects, PDCT comprises a dose of about 25 mg / m2 to about 30 mg / m2 of vinorelbine administered intravenously over about 5 to about 10 minutes on days 1 and 8 of a three-week cycle for about 4 cycles and a dose of about 75 mg / m2 to about 80 mg / m2 of cisplatin administered intravenously over about 60 minutes on Petition 870260055013, dated 08 / 06 / 2026, p. 96 / 490 91 / 189 Day 1 of each cycle. In some aspects, PDCT comprises a dose of approximately 25 mg / m2 of vinorelbine administered intravenously over approximately 5 to 10 minutes on Days 1, 8, 15, and 22 of a four-week cycle for approximately 4 cycles, and a dose of approximately 50 mg / m2 of cisplatin administered intravenously over approximately 60 minutes on Days 1 and 8 of each cycle. In some aspects, PDCT comprises a dose of approximately 30 mg / m2 of vinorelbine administered intravenously over approximately 5 to 10 minutes on Days 1, 8, 15, and 22 of a four-week cycle for approximately 4 cycles, and a dose of approximately 100 mg / m2 of cisplatin administered intravenously over approximately 60 minutes on Day 1 of each cycle.

[00315] In some aspects, PDCT comprises cisplatin and vinblastine. In some aspects, vinblastine is administered at a dose of approximately 5 mg / m2. In some aspects, vinblastine is administered intravenously over approximately 5 to 10 minutes. In some aspects, PDCT comprises a dose of approximately 5 mg / m2 of vinblastine administered intravenously over approximately 5 to 10 minutes on days 1, 8, 15, 22, and 29 of a 35-day cycle and a dose of approximately 100 mg / m2 of cisplatin administered intravenously over approximately 60 minutes on days 1 and 29 of the cycle.

[00316] In some respects, PDCT is administered in combination with bevacizumab (also known as AVASTIN®). In some respects, bevacizumab is administered intravenously at a dose of approximately 15 mg / kg on Day 1 of a three-week cycle for approximately 6 cycles, paclitaxel is administered intravenously at a dose of approximately 200 mg / m2 over approximately 180 minutes on Day 1 of each cycle, and carboplatin is administered intravenously over approximately 30 minutes at a dose to target an AUC of approximately 6 Petition 870260055013, dated 08 / 06 / 2026, p. 97 / 490 92 / 189 mg / mL^min on Day 1 of each cycle. In some respects, bevacizumab is administered intravenously at a dose of approximately 15 mg / kg on Day 1 of a three-week cycle for approximately 4 to 6 cycles, pemetrexed is administered intravenously at a dose of approximately 500 mg / m2 over approximately 10 minutes on Day 1 of each cycle, and carboplatin is administered intravenously over approximately 30 minutes at a dose to target an AUC of approximately 6 mg / mL^min on Day 1 of each cycle. In some respects, bevacizumab is administered intravenously at a dose of approximately 7.5 mg / kg on Day 1 of a three-week cycle for approximately 4 to 6 cycles, pemetrexed is administered intravenously at a dose of approximately 500 mg / m2 over approximately 10 minutes on Day 1 of each cycle, and cisplatin is administered intravenously at a dose of approximately 75 mg / m2 over approximately 60 minutes on Day 1 of each cycle. II.B.2. Therapeutic Agents

[00317] In some respects, the additional therapeutic agent comprises an anticancer agent. In some respects, the anticancer agent comprises a tyrosine kinase inhibitor, an antiangiogenic agent, a checkpoint inhibitor, a checkpoint stimulator, a chemotherapeutic agent, an immunotherapeutic agent, a platinum agent, an alkylating agent, a taxane, a nucleoside analogue, an antimetabolite, a topoisomerase inhibitor, an anthracycline, a vinca alkaloid, or any combination thereof.

[00318] In some respects, the tyrosine kinase inhibitor comprises sorafenib (e.g., sorafenib tosylate, also known as NEXAVAR®), lenvatinib (e.g., lenvatinib mesylate, also known as LENVIMA®), regorafenib (e.g., STIVARGA®), cabozantinib (e.g., cabozantinib S-malate, also known as CABOMETYX®), sunitinib (e.g., sunitinib malate, also known as SUTENT®), briva Petition 870260055013, dated 08 / 06 / 2026, p. 98 / 490 93 / 189 nibe, linifanib, pemigatinib (also known as PEMAZYRETM), everolimus (also known as AFINITOR® or ZORTRESS®), gefitinib (IRESSA®, a small molecule EGFR TKI), imatinib (e.g., imatinib mesylate), lapatinib (e.g., lapatinib ditosylate, also known as TYKERB®), nilotinib (e.g., nilotinib hydrochloride, also known as TASIGNA®), pazopanib (e.g., pazopanib hydrochloride, also known as VOTRIENT®), temsirolimus (also known as TORISEL®), erlotinib (e.g., erlotinib hydrochloride, also known as TARCEVA®, a small molecule EGFR TKI), afatinib (GILOTRIF®, a small molecule TKI). of EGFR), dacomitinib (VIZIMPRO®, a small molecule EGFR TKI), osimeritinib (TAGRISSO®, a small molecule EGFR TKI), alectinib (ALECENSA®, a small molecule ALK TKI), ceritinib (ZYKADIA®, a small molecule ALK and ROS-1 TKI), brigatinib (ALUNBRIG®,a small molecule ALK TKI), crizotinib (XALKORI®, a small molecule ALK and ROS-1 TKI), lorlatinib (LORBRENA®, a small molecule ALK and ROS-1 TKI), entrectinib (ROZLYTREK®, a small molecule ROS-1 and NTRK TKI), dabrafenib (TAFINLAR®, a small molecule BRAF TKI), trametinib (MEKINIST®, a small molecule BRAF TKI), vemurafenib (ZELBORAF®, a small molecule BRAF TKI), larotrectinib (ROZLYTREK®, a small molecule NTRK TKI), or any combination thereof.

[00319] In some respects, the antiangiogenic agent comprises an inhibitor of a vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR), platelet-derived growth factor (PDGF), PDGF receptor (PDGFR), angiopoietin (Ang), tyrosine kinase with Ig-like and EGF-like domain receptors (Tie), hepatocyte growth factor (HGF), tyrosine Petition 870260055013, dated 08 / 06 / 2026, p. 99 / 490 94 / 189 Met protein kinase (c-MET), C-type lectin family 14 member A (CLEC14A), multimerin 2 (MMRN2), shock protein 70-1A (HSP70-1A), an epidermal growth factor (EGF), EGFR, or any combination thereof. In some respects, the antiangiogenic agent comprises bevacizumab (also known as AVASTIN®), ramucirumab (also known as CYRAMZA®), aflibercept (also known as EYLEA® or ZALTRAP®), tanibirumab, olaratumab (also known as LARTRUVO™), nesvacumab, AMG780, MEDI3617, vanucizumab, rilotumumab, ficlatuzumab, TAK-701, onartuzumab, emibetuzumab, or any combination thereof.

[00320] In some respects, the antiangiogenic agent is bevacizumab. In some respects, bevacizumab is administered at a dose of approximately 15 mg / kg. In some respects, bevacizumab is administered at a dose of approximately 15 mg / kg on Day 1 of a three-week cycle.

[00321] In some respects, the checkpoint stimulator comprises an agonist of B7-1, B7-2, CD28, 4-1BB (CD137), 4-1BBL, GITR, inducible T-cell co-stimulator (ICOS), ICOS-L, OX40, OX40L, CD70, CD27, CD40, death receptor 3 (DR3), CD28H or any combination thereof.

[00322] In some respects, the chemotherapeutic agent comprises an alkylating agent, an antimetabolite, an antineoplastic antibiotic, a mitotic inhibitor, a hormone or hormone modulator, a protein tyrosine kinase inhibitor, an epidermal growth factor inhibitor, a proteasome inhibitor, another anti-neoplastic agent, or any combination thereof.

[00323] In some respects, the immunotherapeutic agent comprises an antibody that binds specifically to EGFR (e.g., cetuximab (ERBITUX®)), ALK, ROS-1, NTRK, BRAF, ICOS, CD137 Petition 870260055013, dated 08 / 06 / 2026, page 100 / 490 95 / 189 (4-1BB), CD134 (OX40), NKG2A, CD27, CD96, GITR, Herpes virus entry mediator (HVEM), PD-1, PD-L1, CTLA-4, BTLA, TIM-3, A2aR, Killer cell lectin-like G1 receptor (KLRG-1), Natural killer cell receptor 2B4 (CD244), CD160, TIGIT, VISTA, KIR, TGFe, IL-10, IL-8, B7-H4, Fas ligand, CSF1R, CXCR4, mesothelin, CEACAM-1, CD52, HER2, MICA, MICB, or any combination thereof.

[00324] In some respects, the platinum agent comprises cisplatin, carboplatin, oxaliplatin, satraplatin, picoplatin, nedaplatin, triplatin (e.g., triplatin tetranitrate), lipoplatin, phenanttriplatin, or any combination thereof.

[00325] In some respects, the alkylating agent comprises altretamine, bendamustine, busulfan, carboplatin, carmustine, chlorambucil, cisplatin, cyclophosphamide, dacarbazine, ifosfamide, lomustine, mechlorethamine, melphalan, oxaliplatin, procarbazine, streptozocin, temozolomide, thiotepa or any combination thereof.

[00326] In some respects, taxane comprises paclitaxel, albumin-bound paclitaxel (i.e., nab-paclitaxel), docetaxel, cabazitaxel, or any combination thereof.

[00327] In some aspects, the taxane comprises paclitaxel. In some aspects, paclitaxel is administered intravenously at a dose of about 200 mg / m2 to about 225 mg / m2 over about 180 minutes on Day 1 of a three-week cycle for about 4 to about 6 cycles. In some aspects, paclitaxel is administered intravenously at a dose of about 80 mg / m2 over about 60 minutes on Days 1, 8, and 15 of a four-week cycle for about 4 to about 6 cycles.

[00328] In some respects, the taxane comprises albumin-bound paclitaxel. In some respects, albumin-bound paclitaxel is administered intravenously at a dose of approximately 260 mg / m2 Petition 870260055013, dated 08 / 06 / 2026, p. 101 / 490 96 / 189 for about 30 minutes on Day 1 of a three-week cycle for about 4 to about 6 cycles. In some cases, albumin-bound paclitaxel is administered intravenously at a dose of about 125 mg / m2 for about 30 minutes on Days 1, 8, and 15 of a four-week cycle for about 4 to about 6 cycles.

[00329] In some respects, the taxane comprises docetaxel. In some respects, docetaxel is administered intravenously at a dose of about 75 mg / m2 over about 60 minutes on Day 1 of a three-week cycle. In some respects, docetaxel is administered intravenously at a dose of about 75 mg / m2 over about 60 minutes on Day 1 of a three-week cycle for about 4 to about 6 cycles.

[00330] In some respects, the nucleoside analogue comprises cytarabine, gemcitabine, lamivudine, entecavir, telbivudine or any combination thereof.

[00331] In some respects, the nucleoside analogue is gemcitabine. In some respects, gemcitabine is administered intravenously at a dose of about 1,000 mg / m2 to about 1,250 mg / m2 over about 30 minutes on days 1, 8, and 15 of a four-week cycle. In some respects, gemcitabine is administered intravenously at a dose of about 1,000 mg / m2 to about 1,250 mg / m2 over about 30 minutes on days 1, 8, and 15 of a four-week cycle for about 4 to about 6 cycles. In some respects, gemcitabine is administered intravenously at a dose of about 1,250 mg / m2 over about 30 minutes on days 1 and 8 of a three-week cycle. In some respects, gemcitabine is administered intravenously at a dose of approximately 1,250 mg / m2 over about 30 minutes on days 1 and 8 of a three-week cycle for about 4 to about 6 cycles.

[00332] In some respects, the antimetabolite comprises capeci Petition 870260055013, dated 08 / 06 / 2026, p. 102 / 490 97 / 189 tabina, cladribine, clofarabine, cytarabine, floxuridine, fludarabine, fluorouracil, mercaptopurine, methotrexate, pemetrexed, pentostatin, pralatrexate, thioguanine, or any combination thereof.

[00333] In some respects, the antimetabolite is pemetrexed. In some respects, pemetrexed is administered intravenously at a dose of about 500 mg / m2 over about 10 minutes on Day 1 of a three-week cycle. In some respects, pemetrexed is administered intravenously at a dose of about 500 mg / m2 over about 10 minutes on Day 1 of a three-week cycle for about 4 to about 6 cycles.

[00334] In some embodiments, the topoisomerase inhibitor comprises etoposide, mitoxantrone, doxorubicin, irinotecan, topotecan, camptothecin, or any combination thereof.

[00335] In some respects, anthracycline is doxorubicin, daunorubicin, epirubicin, idarubicin, or any combination thereof.

[00336] In some respects, the vinca alkaloid is vinblastine, vincristine, vinorelbine, vindesine, vincaminol, vineridine, vinburnine, or any combination thereof.

[00337] In some respects, the anticancer agent comprises gemcitabine and docetaxel. In some respects, gemcitabine is administered intravenously at a dose of about 1,000 mg / m2 to about 1,250 mg / m2 over about 30 minutes on Days 1 and 8 of a three-week cycle for about 4 to about 6 cycles, and docetaxel is administered intravenously at a dose of about 85 mg / m2 over about 30 to about 60 minutes on Day 8 of each cycle.

[00338] In some respects, the anticancer agent comprises gemcitabine and vinorelbine. In some respects, gemcitabine is administered intravenously at a dose of approximately 1,000 mg / m2 over approximately 30 minutes on days 1 and 8 of a three-week cycle. Petition 870260055013, dated 08 / 06 / 2026, p. 103 / 490 98 / 189 approximately 4 to approximately 6 cycles and vinorelbine is administered intravenously at a dose of approximately 25 mg / m2 for approximately 5 to 10 minutes on days 1 and 8 of each cycle.

[00339] In some respects, the anticancer agent comprises ramucirumab and docetaxel. In some respects, ramucirumab is administered intravenously at a dose of approximately 10 mg / kg over approximately 60 minutes on Day 1 of a three-week cycle and docetaxel is administered intravenously at a dose of approximately 75 mg / m2 over approximately 60 minutes on Day 1 of each cycle.

[00340] In some respects, the anticancer agent comprises bevacizumab and pemetrexed. In some respects, bevacizumab is administered intravenously at a dose of about 7.5 mg / kg to about 15 mg / kg over about 10 minutes on Day 1 of a three-week cycle, and pemetrexed is administered intravenously at a dose of about 500 mg / m2 over about 10 minutes on Day 1 of each cycle. II.B.3. Checkpoint inhibitors

[00341] In some respects, the anticancer agent that is administered as an additional therapeutic agent in the methods described is a checkpoint inhibitor.

[00342] In some respects, the checkpoint inhibitor comprises a programmed death pathway-1 (PD-1) inhibitor, a cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) inhibitor, a T-cell immunoglobulin and ITIM domain inhibitor (TIGIT), a T-cell immunoglobulin and mucin-containing inhibitor-3 (TIM-3), a TIM-1 inhibitor, a TIM-4 inhibitor, a B7-H3 inhibitor, a B7-H4 inhibitor, a B and T cell lymphocyte attenuator (BTLA), a V-domain Ig-containing T-cell activation suppressor (VISTA) inhibitor, an indoleamine 2,3-dioxygenase (IDO) inhibitor (e.g., an indoleamine 2,3-dioxygenase 1 inhibitor (IDO1)), epacadostat Petition 870260055013, dated 08 / 06 / 2026, page 104 / 490 99 / 189 (INCB24360), navoximod (GDC-0919) or linrodostat (BMS-986205), including a linrodostat salt, such as, for example, linrodostat mesylate), a nicotinamide adenine dinucleotide phosphate oxidase isoform 2 (NOX2) inhibitor, a killer cell immunoglobulin-like receptor (KIR) inhibitor, an adenosine A2a receptor (A2aR) inhibitor, a transforming growth factor beta (TGF-β) inhibitor, a phosphoinositide 3-kinase (PI3K) inhibitor, a CD47 inhibitor, a CD48 inhibitor, a CD73 inhibitor, a CD113 inhibitor, a sialic acid-binding immunoglobulin-type lectin-7 (SIGLEC-7) inhibitor, a SIGLEC-9 inhibitor, a SIGLEC-15 inhibitor, an inhibitor of glucocorticoid-induced TNFR-related protein (GITR), a galectin-1 inhibitor, a galectin-9 inhibitor, a carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM-1) inhibitor, a G protein-coupled receptor 56 inhibitor,a predominant inhibitor of glycoprotein A repeats (GARP), a 2B4 inhibitor, a programmed death homolog 1 (PD1H) inhibitor, a leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) inhibitor, or any combination thereof.

[00343] In some respects, the checkpoint inhibitor is formulated for intravenous administration.

[00344] In some respects, the LAG-3 antagonist and the checkpoint inhibitor are separate. In some respects, each checkpoint inhibitor is separate when the checkpoint inhibitor comprises more than one checkpoint inhibitor. In some respects, the checkpoint inhibitor is administered before the LAG-3 antagonist. In some respects, the LAG-3 antagonist is administered before the checkpoint inhibitor.

[00345] In some respects, the LAG-3 antagonist and the checkpoint inhibitor are linked. In some respects, two or more inhibitors Petition 870260055013, dated 08 / 06 / 2026, page 105 / 490 100 / 189 checkpoints are combined when the checkpoint inhibitor comprises more than one checkpoint inhibitor.

[00346] In some respects, the LAG-3 antagonist and the checkpoint inhibitor are administered simultaneously.

[00347] In some respects, the checkpoint inhibitor is administered at a fixed dose.

[00348] In some respects, the checkpoint inhibitor is administered at a dose of at least about 0.25 mg to about 2000 mg, about 0.25 mg to about 1600 mg, about 0.25 mg to about 1200 mg, about 0.25 mg to about 800 mg, about 0.25 mg to about 400 mg, about 0.25 mg to about 100 mg, about 0.25 mg to about 50 mg, about 0.25 mg to about 40 mg, about 0.25 mg to about 30 mg, about 0.25 mg to about 20 mg, about 20 mg to about 2000 mg, about 20 mg to about 1600 mg, about 20 mg to about 1200 mg, about 20 mg to about 800 mg, about 20 mg to about 400 mg, about 20 mg to about 100 mg, about 100 mg to about 2000 mg, about 100 mg to about 1800 mg, about 100 mg to about 1600 mg, about 100 mg to about 1400 mg, about 100 mg to about 1200 mg, about 100 mg to about 1000 mg, about 100 mg to about 800 mg, about 100 mg to about 600 mg, about 100 mg to about 400 mg,about 400 mg to about 2000 mg, about 400 mg to about 1800 mg, about 400 mg to about 1600 mg, about 400 mg to about 1400 mg, about 400 mg to about 1200 mg or about 400 mg to about 1000 mg.

[00349] In some respects, the checkpoint inhibitor is administered at a dose of approximately 0.25 mg, approximately 0.5 mg, approximately 0.75 mg, approximately 1 mg, approximately 1.25 mg, approximately 1.5 mg, approximately 1.75 mg, approximately 2 mg, approximately 2.25 mg, approximately 2.5 mg, approximately 2.75 mg, approximately 3 mg, approximately 3.25 mg, approximately 3.5 mg, approximately 3.75 Petition 870260055013, dated 08 / 06 / 2026, page 106 / 490 101 / 189 mg, approximately 4 mg, approximately 4.25 mg, approximately 4.5 mg, approximately 4.75 mg, approximately 5 mg, approximately 5.25 mg, approximately 5.5 mg, approximately 5.75 mg, approximately 6 mg, approximately 6.25 mg, approximately 6.5 mg, approximately 6.75 mg, approximately 7 mg, approximately 7.25 mg, approximately 7.5 mg, approximately 7.75 mg, approximately 8 mg, approximately 8.25 mg, approximately 8.5 mg, approximately 8.75 mg, approximately 9 mg, approximately 9.25 mg, approximately 9.5 mg, approximately 9.75 mg, approximately 10 mg, approximately 20 mg, approximately 30 mg, approximately 40 mg, approximately 50 mg, approximately 60 mg, approximately 70 mg, approximately 80 mg, approximately 90 mg, approximately 100 mg, approximately 110 mg, approximately 120 mg, approximately 130 mg, approximately 140 mg, approximately 150 mg, approximately 160 mg, approximately 170 mg, approximately 180 mg, approximately 190 mg, approximately 200 mg, approximately 210 mg, approximately 220 mg, approximately 230 mg, approximately 240 mg, approximately 250 mg, approximately 260 mg, approximately 270 mg, approximately 280 mg, approximately 290 mg, approximately 300 mg, approximately 310 mg, approximately 320 mg, approximately 330 mg, approximately 340 mg, approximately 350 mgapproximately 360 mg, approximately 370 mg, approximately 380 mg, approximately 390 mg, approximately 400 mg, approximately 410 mg, approximately 420 mg, approximately 430 mg, approximately 440 mg, approximately 450 mg, approximately 460 mg, approximately 470 mg, approximately 480 mg, approximately 490 mg, approximately 500 mg, approximately 510 mg, approximately 520 mg, approximately 530 mg, approximately 540 mg, approximately 550 mg, approximately 560 mg, approximately 570 mg, approximately 580 mg, approximately 590 mg, approximately 600 mg, approximately 610 mg, approximately 620 mg, approximately 630 mg, approximately 640 mg, approximately 650 mg, approximately 660 mg, about 670 mg, about 680 mg, about 690 mg, about 700 mg, about 710 mg, about 720 mg, about 730 mg, about 740 mg, about 750 mg, about 760 mg, about 770 mg, about 780 mg, about 790 mg, about 800 mg, about 810 mg, about 820 mg, about 830 mg, about 840 mg, about 850 mg, about 860 mg, about 870 mg, about 880 mg, about 890 mg, about 900 mg, about 910 mg, about 920 Petition 870260055013, dated 08 / 06 / 2026, page 107 / 490 102 / 189 mg, about 930 mg, about 940 mg, about 950 mg, about 960 mg, about 970 mg, about 980 mg, about 990 mg, about 1000 mg, about 1040 mg, about 1080 mg, about 1100 mg, about 1140 mg, about 1180 mg, about 1200 mg, about 1240 mg, about 1280 mg, about 1300 mg, about 1340 mg, about 1380 mg, about 1400 mg, about 1440 mg, about 1480 mg, about 1500 mg, about 1540 mg, about 1580 mg, about 1600 mg, about 1640 mg, about 1680 mg, about 1700 mg, about 1740 mg, about 1780 mg, about 1800 mg, about 1840 mg, about 1880 mg, about 1900 mg, about 1940 mg, approximately 1980 mg, or approximately 2000 mg.

[00350] In some respects, the checkpoint inhibitor is administered as a weight-based method.

[00351] In some aspects, the checkpoint inhibitor is administered at a dose from about 0.003 mg / kg to about 25 mg / kg, about 0.003 mg / kg to about 20 mg / kg, about 0.003 mg / kg to about 15 mg / kg, about 0.003 mg / kg to about 10 mg / kg, about 0.003 mg / kg to about 5 mg / kg, about 0.003 mg / kg to about 1 mg / kg, about 0.003 mg / kg to about 0.9 mg / kg, about 0.003 mg / kg to about 0.8 mg / kg, about 0.003 mg / kg to about 0.7 mg / kg, about 0.003 mg / kg to about 0.6 mg / kg, about 0.003 mg / kg to about 0.5 mg / kg, about 0.003 mg / kg to about 0.4 mg / kg, about 0.003 mg / kg to about 0.3 mg / kg, about 0.003 mg / kg to about 0.2 mg / kg, about 0.003 mg / kg to about 0.1 mg / kg, about 0.1 mg / kg to about 25 mg / kg, about 0.1 mg / kg to about 20 mg / kg, about 0.1 mg / kg to about 15 mg / kg, about 0.1 mg / kg to about 10 mg / kg, about 0.1 mg / kg to about 5 mg / kg, about 0.1 mg / kg to about 1 mg / kg,about 1 mg / kg to about 25 mg / kg, about 1 mg / kg to about 20 mg / kg, about 1 mg / kg to about 15 mg / kg, about 1 mg / kg to about 10 mg / kg, Petition 870260055013, dated 08 / 06 / 2026, page 108 / 490 103 / 189 about 1 mg / kg to about 5 mg / kg, about 5 mg / kg to about 25 mg / kg, about 5 mg / kg to about 20 mg / kg, about 5 mg / kg to about 15 mg / kg, about 5 mg / kg to about 10 mg / kg, about 10 mg / kg to about 25 mg / kg, about 10 mg / kg to about 20 mg / kg, about 10 mg / kg to about 15 mg / kg, about 15 mg / kg to about 25 mg / kg, about 15 mg / kg to about 20 mg / kg, or about 20 mg / kg to about 25 mg / kg.

[00352] In some aspects, the checkpoint inhibitor is administered at a dose of approximately 0.003 mg / kg, approximately 0.004 mg / kg, approximately 0.005 mg / kg, approximately 0.006 mg / kg, approximately 0.007 mg / kg, approximately 0.008 mg / kg, approximately 0.009 mg / kg, approximately 0.01 mg / kg, approximately 0.02 mg / kg, approximately 0.03 mg / kg, approximately 0.04 mg / kg, approximately 0.05 mg / kg, approximately 0.06 mg / kg, approximately 0.07 mg / kg, approximately 0.08 mg / kg, approximately 0.09 mg / kg, approximately 0.1 mg / kg, approximately 0.2 mg / kg, approximately 0.3 mg / kg, approximately 0.4 mg / kg, about 0.5 mg / kg, about 0.6 mg / kg, about 0.7 mg / kg, about 0.8 mg / kg, about 0.9 mg / kg, about 1.0 mg / kg, about 2.0 mg / kg, about 3.0 mg / kg, about 4.0 mg / kg, about 5.0 mg / kg, about 6.0 mg / kg, about 7.0 mg / kg, about 8.0 mg / kg, about 9.0 mg / kg, about 10.0 mg / kg, about 11.0 mg / kg, about 12.0 mg / kg, about 13.0 mg / kg, about 14.0 mg / kg, about 15.0 mg / kg, about 16.0 mg / kg, about 17.0 mg / kg, about 18.0 mg / kg, approximately 19.0 mg / kgapproximately 20.0 mg / kg, approximately 21.0 mg / kg, approximately 22.0 mg / kg, approximately 23.0 mg / kg, approximately 24.0 mg / kg, or approximately 25.0 mg / kg.

[00353] In some respects, the dose of the checkpoint inhibitor is administered every one week, every two weeks, every three weeks, every four weeks, every five weeks, every six weeks, every seven weeks, every eight weeks, every nine weeks, every ten weeks, every eleven weeks, or every twelve weeks. Petition 870260055013, dated 08 / 06 / 2026, p. 109 / 490 104 / 189 weeks.

[00354] In some respects, each dose of the LAG-3 antagonist and / or checkpoint inhibitor is administered in a constant amount.

[00355] In some respects, each dose of the LAG-3 antagonist and / or checkpoint inhibitor is administered in a variable amount. For example, in some respects, the maintenance (or continuation) dose of the LAG-3 antagonist and / or checkpoint inhibitor may be greater than or equal to the loading dose that is administered first. In some respects, the maintenance dose of the LAG-3 antagonist and / or checkpoint inhibitor may be less than or equal to the loading dose. II.B.3. a. PD-1 pathway inhibitors

[00356] In some respects, the checkpoint inhibitor for use in the methods described comprises an inhibitor of the PD-1 pathway.

[00357] In some respects, the PD-1 pathway inhibitor is a PD-1 inhibitor and / or a PD-L1 inhibitor.

[00358] In some respects, the PD-1 inhibitor and / or PDL1 inhibitor is a small molecule.

[00359] In some respects, the PD-1 inhibitor and / or PDL1 inhibitor is a single molecule.

[00360] In some respects, PD-1 inhibitor and / or PDL1 inhibitor is a macrocyclic peptide.

[00361] In some respects, the PD-1 inhibitor and / or PDL1 inhibitor is BMS-986189.

[00362] In some respects, the PD-1 inhibitor is an inhibitor described in International Publication No. WO2014 / 151634, which is incorporated herein by reference in its entirety.

[00363] In some respects, the PD-1 inhibitor is INCMGA00012 (Insight Pharmaceuticals). Petition 870260055013, dated 08 / 06 / 2026, page 110 / 490 105 / 189

[00364] In some respects, the PD-1 inhibitor comprises a combination of an anti-PD-1 antibody described herein and a small molecule PD-1 inhibitor.

[00365] In some respects, the PD-L1 inhibitor comprises a millimolecule with a formula shown in formula (I): wherein R1-R13 are amino acid side chains, Ra-RN are hydrogen, methyl or form a ring with a vicinal R group, and R14 is -C(O)NHR15, wherein R15 is hydrogen or a glycine residue optionally substituted by additional glycine residues and / or tails that may improve pharmacokinetic properties. In some respects, the PD-L1 inhibitor comprises a compound described in International Publication No. WO2014 / 151634, which is incorporated herein by reference in its entirety. In some respects, the PD-L1 inhibitor comprises a compound described in International Publication No. WO2017 / 176608, WO2018 / 085750, WO2018 / 237153 or WO2019 / 070643, each of which is incorporated herein in its entirety by reference.

[00366] In some respects, the PD-L1 inhibitor comprises a small molecule PD-L1 inhibitor described in Publication InterPetition 870260055013, dated 08 / 06 / 2026, p. 111 / 490 106 / 189 national N° WO2015 / 034820, WO2015 / 160641, WO2018 / 044963, WO2017 / 066227, WO2018 / 009505, WO2018 / 183171, WO2018 / 118848, WO2019 / 147662 or WO2019 / 169123, each of which is incorporated herein in its entirety by reference.

[00367] In some respects, the PD-1 pathway inhibitor is a soluble PD-L2 polypeptide. In some respects, the soluble PD-L2 polypeptide is a fusion polypeptide. In some respects, the soluble PD-L2 polypeptide comprises a ligand-binding fragment of the PD-L2 extracellular domain. In some respects, the soluble PD-L2 polypeptide further comprises a half-life extension portion. In some respects, the half-life extension portion comprises an immunoglobulin constant region or a portion thereof, an immunoglobulin-binding polypeptide, immunoglobulin G (IgG), albumin-binding polypeptide (ABP), a PASylation portion, a HESylation portion, XTEN, a PEGuiylation portion, an Fc region, or any combination thereof. In some respects, the soluble PD-L2 polypeptide is AMP-224 (see, for example, US 2013 / 0017199).

[00368] In some respects, the PD-1 pathway inhibitor is an anti-PD-1 antibody and / or an anti-PD-L1 antibody. II.B.3. ai Anti-PD-1 antibodies

[00369] Anti-PD-1 antibodies known in the art can be used in the methods of the description. Several human monoclonal antibodies that specifically bind PD-1 with high affinity have been described in U.S. Patent No. 8,008,449. Human anti-PD-1 antibodies described in U.S. Patent No. 8,008,449 have been shown to exhibit one or more of the following characteristics: (a) they bind to human PD-1 with a Kd of 1 x 10⁻⁷ M or less, as determined by surface plasmon resonance using a Biacore biosensor system; (b) they do not bind substances Petition 870260055013, dated 08 / 06 / 2026, page 112 / 490 107 / 189 specifically to CD28, CTLA-4 or human ICOS; (c) increase T cell proliferation in a lymphocyte mixed reaction (MLR) assay; (d) increase interferon-γ production in an MLR assay; (e) increase IL-2 secretion in an MLR assay; (f) bind to human PD-1 and cynomolgus monkey PD-1; (g) inhibit the binding of PDL1 and / or PD-L2 to PD-1; (h) stimulate antigen-specific memory responses; (i) stimulate antibody responses; and (j) inhibit tumor cell growth in vivo. The anti-PD-1 antibodies usable in the present invention include monoclonal antibodies that bind specifically to human PD-1 and exhibit at least one, in some respects, at least five, of the preceding features.

[00370] Other anti-PD-1 monoclonal antibodies that can be used in the methods of the description have been described, for example, in U.S. Patents 6,808,710, 7,488,802, 8,168,757 and 8,354,509, U.S. Publication No. 2016 / 0272708 and PCT Publication Nos. WO 2012 / 145493, WO 2008 / 156712, WO 2015 / 112900, WO 2012 / 145493, WO 2015 / 112800, WO 2014 / 206107, WO 2015 / 35606, WO 2015 / 085847, WO 2014 / 179664, WO 2017 / 020291, WO 2017 / 020858, WO 2016 / 197367, WO 2017 / 024515, WO 2017 / 025051, WO 2017 / 123557, WO 2016 / 106159, WO 2014 / 194302, WO 2017 / 040790, WO 2017 / 133540, WO 2017 / 132827, WO 2017 / 024465, WO 2017 / 025016, WO 2017 / 106061, WO 2017 / 19846, WO 2017 / 024465, WO 2017 / 025016, WO 2017 / 132825, and WO 2017 / 133540, each of which is incorporated by reference in its entirety.

[00371] Anti-PD-1 antibodies that can be used in the methods described include nivolumab (also known as OPDIVO®, 5C4, BMS-936558, MDX-1106 and ONO-4538), pembrolizumab (Merck; also known as KEYTRUDA®, lambrolizumab and MK3475; see WO 2008 / 156712), PDR001 (Novartis; also known Petition 870260055013, dated 08 / 06 / 2026, page 113 / 490 108 / 189 as espartalizumab; see WO 2015 / 112900 and U.S. Patent No. 9,683,048), MEDI-0680 (AstraZeneca; also known as AMP-514; see WO 2012 / 145493), TSR-042 (Tesaro Biopharmaceutical; also known as ANB011 or dostarlimab; see WO 2014 / 179664), cemiplimab (Regeneron; also known as LIBTAYO® or REGN-2810; see WO 2015 / 112800 and U.S. Patent 9,987,500), JS001 (TAIZHOU JUNSHI PHARMA; also known as toripalimab; see, Si-Yang Liu et al., J. Hematol. Oncol. 10: 136 (2017)), PF-06801591 (Pfizer; also known as sasanlimab; US 2016 / 0159905), BGB-A317 (Beigene; also known as tislelizumab; see WO 2015 / 35606 and US 2015 / 0079109), BI 754091 (Boehringer Ingelheim; see Zettl M et al., Cancer. Res. (2018); 78(13 Suppl): Abstract 4558), INCSHR1210 (Jiangsu Hengrui Medicine; also known as SHR-1210 or camrelizumab; see WO 2015 / 085847; Si-Yang Liu et al., J. Hematol. Oncol. 10: 136 (2017)), GLS-010 (Wuxi / Harbin Gloria Pharmaceuticals; also known as WBP3055; see, Si-Yang Liu et al., J. Hematol. Oncol. 10: 136 (2017)), AM-0001 (Armo), STI-1110 (Sorrento Terapêutica; see, WO 2014 / 194302), AGEN2034 (Agenus; see, WO 2017 / 040790), MGA012 (Macrogenics, see, WO 2017 / 19846), BCD100 (Biocad; Kaplon et al., mAbs 10(2): 183-203 (2018), IBI308 (Innovent; also known as sintilimab; see WO 2017 / 024465, WO 2017 / 025016, WO 2017 / 132825 and WO 2017 / 133540) and SSI-361 (Lyvgen Biopharma Holdings Limited, US 2018 / 0346569).

[00372] Anti-PD-1 antibodies that may be used in the methods of the description also include isolated antibodies that specifically bind to human PD-1 and cross-compete for binding to human PD-1 with any anti-PD-1 antibody described herein, for example, nivolumab (see, for example, U.S. Patent Nos. 8,008,449 and 8,779,105; WO 2013 / 173223). In some Petition 870260055013, dated 08 / 06 / 2026, p. 114 / 490 109 / 189 aspects, the anti-PD-1 antibody binds to the same epitope as any of the anti-PD-1 antibodies described here, for example, nivolumab.

[00373] In some respects, antibodies that cross-compete for binding to human PD-1 or bind to the same epitope region as any anti-PD-1 antibody described herein, for example, nivolumab, are monoclonal antibodies. For administration to humans, these cross-competing antibodies are chimeric antibodies, modified antibodies, or humanized or human antibodies. Such chimeric, modified, humanized, or human monoclonal antibodies can be prepared and isolated by methods well known in the art.

[00374] The anti-PD-1 antibodies that can be used in the methods described also include antigen-binding moieties of any of the above full-size antibodies.

[00375] The anti-PD-1 antibodies that can be used in the methods described are antibodies that bind to PD-1 with high specificity and affinity, block the binding of PD-L1 and / or PD-L2, and inhibit the immunosuppressive effect of the PD-1 signaling pathway. In any of the compositions or methods described herein, an anti-PD-1 antibody includes an antigen-binding portion or fragment that binds to the PD-1 receptor and exhibits functional properties similar to those of whole antibodies in inhibiting ligand binding and positively regulating the immune system. In certain respects, the anti-PD-1 antibody or its antigen-binding portion cross-competes with nivolumab for binding to human PD-1.

[00376] In some respects, the anti-PD-1 antibody is a full-size antibody. In some respects, the anti-PD-1 antibody is a monoclonal, human, humanized, chimeric, or multispecific antibody. In some respects, the multispecific antibody is a DART, Petition 870260055013, dated 08 / 06 / 2026, page 115 / 490 110 / 189 a DVD-Ig or bispecific antibody.

[00377] In some respects, the anti-PD-1 antibody is an F(ab')2 fragment, a Fab' fragment, a Fab fragment, an Fv fragment, an scFv fragment, a dsFv fragment, a dAb fragment, or a single-chain binding polypeptide.

[00378] In some respects, the anti-PD-1 antibody is nivolumab, pembrolizumab, PDR001 (spartalizumab), MEDI-0680, TSR-042, cemiplimab, JS001, PF-06801591, BGB-A317, BI 754091, INCSHR1210, GLS-010, AM-001, STI-1110, AGEN2034, MGA012, BCD100, IBI308, SSI-361, or including an antigen-binding portion thereof.

[00379] In some respects, the anti-PD-1 antibody is formulated for intravenous administration.

[00380] In some aspects, the anti-PD-1 antibody is administered intravenously over approximately 30 minutes.

[00381] In some respects, the anti-PD-1 antibody is nivolumab. Nivolumab is a fully human IgG4 (S228P) antibody that inhibits the PD-1 immune checkpoint and selectively avoids interaction with PD-1 ligands (PD-L1 and PD-L2), thereby blocking the downregulation of antitumor T cell functions (U.S. Patent No. 8,008,449; Wang et al., 2014 Cancer Immunol Res. 2(9): 846-56).

[00382] In some respects, nivolumab is administered at a flat dose of approximately 240 mg once every 2 weeks. In some respects, nivolumab is administered at a flat dose of approximately 240 mg once every 3 weeks. In some respects, nivolumab is administered at a fixed dose of approximately 360 mg once every 3 weeks. In some respects, nivolumab is administered at a fixed dose of approximately 480 mg once every 4 weeks. Petition 870260055013, dated 08 / 06 / 2026, p. 116 / 490 111 / 189

[00383] In some respects, nivolumab is administered intravenously at a dose of approximately 240 mg over about 30 minutes on Day 1 of a two-week cycle.

[00384] In some respects, nivolumab is administered intravenously at a dose of approximately 480 mg over about 30 minutes on Day 1 of a four-week cycle.

[00385] In some respects, the methods of the description comprise an anti-PD-1 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence shown in SEQ ID No: 13 and the CDR1, CDR2 and CDR3 domains of the variable light chain region having the sequence shown in SEQ ID No: 14.

[00386] In some respects, the methods of the description comprise an anti-PD-1 antibody comprising: (a) a CDR1 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 15; (b) a CDR2 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 16; (c) a CDR3 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 17; (d) a CDR1 of the variable light chain region comprising the sequence presented in SEQ ID No: 18; (e) a CDR2 of the variable light chain region comprising the sequence presented in SEQ ID No: 19; and (f) a CDR3 of the variable light chain region comprising the sequence presented in SEQ ID No: 20.

[00387] In some respects, the methods of the description comprise an anti-PD-1 antibody comprising variable regions of heavy and light chains comprising the sequences as presented in SEQ ID Nos: 13 and 14, respectively.

[00388] In some respects, the methods of the invention comprise an anti-PD-1 antibody comprising heavy and light chains. Petition 870260055013, dated 08 / 06 / 2026, page 117 / 490 112 / 189 comprising the sequences as set forth in SEQ ID Nos. 11 and 12, respectively.

[00389] In some respects, the methods of the invention comprise a combination of relatlimab and nivolumab.

[00390] In some respects, the methods of the description comprise: (a) an anti-LAG-3 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No: 3 and the CDR1, CDR2 and CDR3 domains of the variable light chain region with the sequence presented in SEQ ID No: 4; and (b) an anti-PD-1 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No: 13 and the CDR1, CDR2 and CDR3 domains of the variable light chain region with the sequence presented in SEQ ID No: 14.

[00391] In some respects, the methods of the description comprise: (a) an anti-LAG-3 antibody comprising a CDR1, CDR2 and CDR3 of the variable heavy chain region comprising the sequence presented in SEQ ID No. 5, SEQ ID No. 6, and SEQ ID No. 7, respectively, and a CDR1, CDR2 and CDR3 of the variable light chain region comprising the sequence presented in SEQ ID No. 8, SEQ ID No. 9 and SEQ ID No. 10, respectively, and (b) an anti-PD-1 antibody comprising a CDR1, CDR2 and CDR3 of the variable heavy chain region comprising the sequence presented in SEQ ID No. 15, SEQ ID No. 16 and SEQ ID No. 17, respectively, and a CDR1, CDR2 and CDR3 of the variable light chain region comprising the sequence presented in SEQ ID No. 18, SEQ ID N°: 19 and SEQ ID N°: 20, respectively.

[00392] In some respects, the methods of description comprise: (a) an anti-LAG-3 antibody comprising variable heavy and light chain regions comprising the sequences presented Petition 870260055013, dated 08 / 06 / 2026, p. 118 / 490 113 / 189 in SEQ ID Nos. 3 and 4, respectively, and (b) an anti-PD-1 antibody comprising variable heavy and light chain regions comprising the sequences shown in SEQ ID Nos. 13 and 14, respectively.

[00393] In some respects, the methods of the description comprise: (a) an anti-LAG-3 antibody comprising heavy and light chains comprising the sequences presented in SEQ ID Nos. 1 and 2, respectively, and (b) an anti-PD-1 antibody comprising heavy and light chains comprising the sequences presented in SEQ ID Nos. 11 and 12, respectively.

[00394] In some respects, the methods of the description comprise: (a) an anti-LAG-3 antibody comprising heavy and light chains comprising the sequences presented in SEQ ID Nos. 21 and 2, respectively, and (b) an anti-PD-1 antibody comprising heavy and light chains comprising the sequences presented in SEQ ID Nos. 11 and 12, respectively.

[00395] In some respects, the anti-PD-1 antibody is pembrolizumab. Pembrolizumab is a humanized IgG4 monoclonal antibody (S228P) directed against the human cell surface receptor PD-1. Pembrolizumab is described, for example, in U.S. Patents Nos. 8,354,509 and 8,900,587.

[00396] In some aspects, pembrolizumab is administered at a flat dose of approximately 200 mg once every 2 weeks. In some aspects, pembrolizumab is administered at a flat dose of approximately 200 mg once every 3 weeks. In some aspects, pembrolizumab is administered at a flat dose of approximately 400 mg once every 6 weeks. In some aspects, pembrolizumab is administered at a flat dose of approximately 300 mg once every 4-5 weeks.

[00397] In some respects, pembrolizumab is administered by Petition 870260055013, dated 08 / 06 / 2026, p. 119 / 490 114 / 189 intravenously at a dose of approximately 200 mg on Day 1, then once every 3 weeks. In some respects, pembrolizumab is administered for up to 35 cycles. In some respects, pembrolizumab is administered intravenously at a dose of approximately 200 mg over about 30 minutes on Day 1 of a three-week cycle for up to 35 cycles.

[00398] In some aspects, pembrolizumab is administered intravenously at a dose of approximately 200 mg over about 30 minutes on Day 1 of a three-week cycle for up to 35 cycles, and pemetrexed is administered intravenously at a dose of approximately 500 mg / m2 over about 10 minutes on Day 1 of each cycle, followed by maintenance therapy with pemetrexed at a dose of approximately 500 mg / m2 administered intravenously on Day 1 of a three-week cycle. In some modalities, maintenance therapy continues until disease progression or unacceptable toxicity.

[00399] In some respects, pembrolizumab is administered intravenously at a dose of about 200 mg over about 30 minutes on Day 1 of a three-week cycle for about 4 to about 6 cycles, pemetrexed is administered intravenously at a dose of about 500 mg / m2 over about 10 minutes on Day 1 of each cycle, and carboplatin is administered intravenously over about 30 minutes at a dose to a target AUC of about 5 mg / mL^min on Day 1 of each cycle.

[00400] In some respects, pembrolizumab is administered intravenously at a dose of about 200 mg over about 30 minutes on Day 1 of a three-week cycle for about 4 to about 6 cycles, pemetrexed is administered intravenously at a dose of about 500 mg / m2 over about 10 minutes on Day 1 of each cycle, and cisplatin is administered intravenously at a dose of about 75 mg / m2 over about 60 minutes on Day 1 of each cycle. Petition 870260055013, dated 08 / 06 / 2026, p. 120 / 490 115 / 189

[00401] In some respects, pembrolizumab is administered intravenously at a dose of about 200 mg over about 30 minutes on Day 1 of a three-week cycle for about 4 cycles, albumin-bound paclitaxel is administered intravenously at a dose of about 100 mg / m2 over about 30 minutes on Days 1, 8, and 15 of each cycle, and carboplatin is administered intravenously over about 30 minutes at a dose to a target AUC of about 6 mg / mL^min on Day 1 of each cycle.

[00402] In some respects, pembrolizumab is administered intravenously at a dose of about 200 mg over about 30 minutes on Day 1 of a three-week cycle for about 4 cycles, paclitaxel is administered intravenously at a dose of about 200 mg / m2 over about 180 minutes on Day 1 of each cycle, and carboplatin is administered intravenously over about 30 minutes at a dose to a target AUC of about 6 mg / mL*min on Day 1 of each cycle.

[00403] In some respects, pembrolizumab is administered intravenously at a dose of about 200 mg over about 30 minutes on Day 1 of a three-week cycle for about 4 cycles, albumin-bound paclitaxel is administered intravenously at a dose of about 100 mg / m2 over about 30 minutes on Days 1, 8, and 15 of each cycle, and cisplatin is administered intravenously at a dose of about 75 mg / m2 to about 80 mg / m2 over about 60 minutes on Day 1 of each cycle.

[00404] In some respects, pembrolizumab is administered intravenously at a dose of approximately 200 mg over about 30 minutes on Day 1 of a three-week cycle for approximately 4 cycles, paclitaxel is administered intravenously at a dose of approximately 200 mg / m2 over about 180 minutes on Day 1 of each cycle, and cisplatin is administered intravenously at a dose of approximately 75 Petition 870260055013, dated 08 / 06 / 2026, p. 121 / 490 116 / 189 mg / m2 to about 80 mg / m2 for about 60 minutes on Day 1 of each cycle.

[00405] In some aspects, the methods of the invention comprise an anti-PD-1 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence shown in SEQ ID No: 79 and the CDR1, CDR2 and CDR3 domains of the variable light chain region having the sequence shown in SEQ ID No: 80.

[00406] In some respects, the methods of the invention comprise an anti-PD-1 antibody comprising: (a) a CDR1 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 81; (b) a CDR2 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 82; (c) a CDR3 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 83; (d) a CDR1 of the variable light chain region comprising the sequence presented in SEQ ID No: 84; (e) a CDR2 of the variable light chain region comprising the sequence presented in SEQ ID No: 85; and (f) a CDR3 of the variable light chain region comprising the sequence presented in SEQ ID No: 86.

[00407] In some respects, the methods of the invention comprise an anti-PD-1 antibody comprising variable heavy and light chain regions comprising the sequences presented in SEQ ID Nos. 79 and 80, respectively.

[00408] In some respects, the methods of the invention comprise an anti-PD-1 antibody comprising heavy and light chains comprising the sequences as presented in SEQ ID Nos. 77 and 78, respectively.

[00409] In some respects, the methods of the invention comprise a combination of favezelimab and pembrolizumab. In some Petition 870260055013, dated 08 / 06 / 2026, p. 122 / 490 In some aspects, 800 mg of favezelimab and 200 mg of pembrolizumab are administered intravenously on Day 1, then once every 3 weeks. In some aspects, the combination of favezelimab and pembrolizumab is administered for up to 35 cycles. In some aspects, 800 mg of favezelimab and 200 mg of pembrolizumab are administered intravenously over approximately 30 minutes on Day 1 of a three-week cycle for up to 35 cycles.

[00410] In some respects, the methods of the invention comprise: (a) an anti-LAG-3 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No: 69 and the CDR1, CDR2 and CDR3 domains of the variable light chain region with the sequence presented in SEQ ID No: 70; and (b) an anti-PD-1 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No: 79 and the CDR1, CDR2 and CDR3 domains of the variable light chain region with the sequence presented in SEQ ID No: 80.

[00411] In some respects, the methods of the invention comprise: (a) an anti-LAG-3 antibody comprising a CDR1, CDR2 and CDR3 of the variable heavy chain region comprising the sequence shown in SEQ ID No: 71, SEQ ID No: 72, and SEQ ID No: 73, respectively, and a CDR1, CDR2 and CDR3 of the variable light chain region comprising the sequence shown in SEQ ID No: 74, SEQ ID No: 75 and SEQ ID No: 76, respectively, and (b) an anti-PD-1 antibody comprising a CDR1, CDR2 and CDR3 of the variable heavy chain region comprising the sequence shown in SEQ ID No: 81, SEQ ID No: 82 and SEQ ID No: 83, respectively, and a CDR1, CDR2 and CDR3 of the variable light chain region comprising the sequence shown in SEQ ID No: 84, SEQ ID NO: 85 and SEQ ID NO: 86, respectively. Petition 870260055013, dated 08 / 06 / 2026, p. 123 / 490 118 / 189

[00412] In some respects, the methods of the invention comprise: (a) an anti-LAG-3 antibody comprising variable heavy and light chain regions comprising the sequences presented in SEQ ID Nos. 69 and 70, respectively, and (b) an anti-PD1 antibody comprising variable heavy and light chain regions comprising the sequences presented in SEQ ID Nos. 79 and 80, respectively.

[00413] In some respects, the methods of the invention comprise: (a) an anti-LAG-3 antibody comprising heavy and light chains comprising the sequences presented in SEQ ID Nos. 67 and 68, respectively, and (b) an anti-PD-1 antibody comprising heavy and light chains comprising the sequences presented in SEQ ID Nos. 77 and 78, respectively.

[00414] In some respects, the anti-PD-1 antibody is cemiplimab (REGN2810). Cemiplimab is described, for example, in WO 2015 / 112800 and U.S. Patent No. 9,987,500.

[00415] In some respects, cemiplimab is administered intravenously at a dose of approximately 3 mg / kg or approximately 350 mg once every 3 weeks.

[00416] In some aspects, the methods of the invention comprise an anti-PD-1 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No: 35 and the CDR1, CDR2 and CDR3 domains of the variable light chain region having the sequence presented in SEQ ID No: 36.

[00417] In some respects, the methods of the invention comprise an anti-PD-1 antibody comprising: (a) a CDR1 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 37; (b) a CDR2 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 38; (c) a Petition 870260055013, dated 08 / 06 / 2026, page 124 / 490 119 / 189 (a) a CDR3 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 39; (b) a CDR1 of the variable light chain region comprising the sequence presented in SEQ ID No: 40; (c) a CDR2 of the variable light chain region comprising the sequence presented in SEQ ID No: 41; and (d) a CDR3 of the variable light chain region comprising the sequence presented in SEQ ID No: 42.

[00418] In some respects, the methods of the invention comprise an anti-PD-1 antibody comprising variable heavy and light chain regions comprising the sequences presented in SEQ ID Nos. 35 and 36, respectively.

[00419] In some respects, the methods of the invention comprise an anti-PD-1 antibody comprising heavy and light chains comprising the sequences presented in SEQ ID Nos. 33 and 34, respectively.

[00420] In some respects, the methods of the invention comprise a combination of fianlimab and cemiplimab.

[00421] In some respects, the methods of the invention comprise: (a) an anti-LAG-3 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No: 25 and CDR1, CDR2 and CDR3 domains of the variable light chain region with the sequence presented in SEQ ID No: 26; and (b) an anti-PD-1 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No: 35, and CDR1, CDR2 and CDR3 domains of the variable light chain region with the sequence presented in SEQ ID No: 36.

[00422] In some respects, the methods of the invention comprise: (a) an anti-LAG-3 antibody comprising a CDR1, CDR2 and CDR3 of the variable heavy chain region comprising the Petition 870260055013, dated 08 / 06 / 2026, page 125 / 490 (a) a sequence presented in SEQ ID No. 27, SEQ ID No. 28, and SEQ ID No. 29, respectively, and a CDR1, CDR2, and CDR3 of the variable light chain region comprising the sequence presented in SEQ ID No. 30, SEQ ID No. 31, and SEQ ID No. 32, respectively, and (b) an anti-PD-1 antibody comprising a CDR1, CDR2, and CDR3 of the variable heavy chain region comprising the sequence shown in SEQ ID No. 37, SEQ ID No. 38, and SEQ ID No. 39, respectively, and a CDR1, CDR2, and CDR3 of the variable light chain region comprising the sequence shown in SEQ ID No. 40, SEQ ID No. 41, and SEQ ID No. 42, respectively.

[00423] In some respects, the methods of the invention comprise: (a) an anti-LAG-3 antibody comprising variable heavy and light chain regions comprising the sequences presented in SEQ ID Nos. 25 and 26, respectively, and (b) an anti-PD1 antibody comprising variable heavy and light chain regions comprising the sequences presented in SEQ ID Nos. 35 and 36, respectively.

[00424] In some respects, the methods of the invention comprise: (a) an anti-LAG-3 antibody comprising heavy and light chains comprising the sequences presented in SEQ ID Nos. 23 and 24, respectively, and (b) an anti-PD-1 antibody comprising heavy and light chains comprising the sequences presented in SEQ ID Nos. 33 and 34, respectively.

[00425] In some respects, the anti-PD-1 antibody is spartalizumab (PDR001). Spartalizumab is described, for example, in document WO 2015 / 112900 and in U.S. Patent No. 9,683,048.

[00426] In some respects, espartalizumab is administered intravenously at a dose of approximately 300 mg once every 3 weeks or 400 mg once every 4 weeks.

[00427] In some respects, the methods of the invention comprise Petition 870260055013, dated 08 / 06 / 2026, page 126 / 490 121 / 189 is an anti-PD-1 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence shown in SEQ ID No: 59 and the CDR1, CDR2 and CDR3 domains of the variable light chain region having the sequence shown in SEQ ID No: 60.

[00428] In some respects, the methods of the invention comprise an anti-PD-1 antibody comprising: (a) a CDR1 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 61; (b) a CDR2 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 62; (c) a CDR3 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 63; (d) a CDR1 of the variable light chain region comprising the sequence presented in SEQ ID No: 64; (e) a CDR2 of the variable light chain region comprising the sequence presented in SEQ ID No: 65; and (f) a CDR3 of the variable light chain region comprising the sequence presented in SEQ ID No: 66.

[00429] In some respects, the methods of the invention comprise an anti-PD-1 antibody comprising variable heavy and light chain regions comprising the sequences presented in SEQ ID Nos. 59 and 60, respectively.

[00430] In some respects, the methods of the invention comprise an anti-PD-1 antibody comprising heavy and light chains comprising the sequences as presented in SEQ ID Nos. 57 and 58, respectively.

[00431] In some respects, the methods of the invention comprise a combination of ieramilimab and espartalizumab. In some respects, ieramilimab is administered intravenously at a dose of about 400 mg once every three weeks and espartalizumab is administered intravenously at a dose of about 300 mg. Petition 870260055013, dated 08 / 06 / 2026, p. 127 / 490 122 / 189 mg once every 3 weeks. In some respects, ieramilimab is administered intravenously at a dose of approximately 600 mg once every four weeks, and espartalizumab is administered intravenously at a dose of approximately 400 mg once every 4 weeks.

[00432] In some respects, the methods of the invention comprise: (a) an anti-LAG-3 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No: 47 and CDR1, CDR2 and CDR3 domains of the variable light chain region with the sequence presented in SEQ ID No: 49; and (b) an anti-PD-1 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No: 59, and CDR1, CDR2 and CDR3 domains of the variable light chain region with the sequence presented in SEQ ID No: 60.

[00433] In some respects, the methods of the invention comprise: (a) an anti-LAG-3 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No: 48 and CDR1, CDR2 and CDR3 domains of the variable light chain region with the sequence presented in SEQ ID No: 50; and (b) an anti-PD-1 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No: 59, and CDR1, CDR2 and CDR3 domains of the variable light chain region with the sequence presented in SEQ ID No: 60.

[00434] In some respects, the methods of the invention comprise: (a) an anti-LAG-3 antibody comprising a CDR1, CDR2 and CDR3 of the variable heavy chain region comprising the sequence presented in SEQ ID No: 51, SEQ ID No: 52, and SEQ ID No: 53, respectively, and a CDR1, CDR2 and CDR3 of the variable region of Petition 870260055013, dated 08 / 06 / 2026, page 128 / 490 (a) a light chain comprising the sequence shown in SEQ ID No. 54, SEQ ID No. 55 and SEQ ID No. 56, respectively, and (b) an anti-PD-1 antibody comprising a CDR1, CDR2 and CDR3 of the variable region of the heavy chain comprising the sequence shown in SEQ ID No. 61, SEQ ID No. 62 and SEQ ID No. 63, respectively, and a CDR1, CDR2 and CDR3 of the variable region of the light chain comprising the sequence shown in SEQ ID No. 64, SEQ ID No. 65 and SEQ ID No. 66, respectively.

[00435] In some respects, the methods of the invention comprise: (a) an anti-LAG-3 antibody comprising variable heavy and light chain regions comprising the sequences presented in SEQ ID Nos. 47 and 49, respectively, and (b) an anti-PD1 antibody comprising variable heavy and light chain regions comprising the sequences presented in SEQ ID Nos. 59 and 60, respectively.

[00436] In some respects, the methods of the invention comprise: (a) an anti-LAG-3 antibody comprising variable heavy and light chain regions comprising the sequences presented in SEQ ID Nos. 48 and 50, respectively, and (b) an anti-PD1 antibody comprising variable heavy and light chain regions comprising the sequences presented in SEQ ID Nos. 59 and 60, respectively.

[00437] In some respects, the methods of the invention comprise: (a) an anti-LAG-3 antibody comprising heavy and light chains comprising the sequences presented in SEQ ID Nos. 43 and 45, respectively, and (b) an anti-PD-1 antibody comprising heavy and light chains comprising the sequences presented in SEQ ID Nos. 57 and 58, respectively.

[00438] In some respects, the methods of the invention comprise: (a) an anti-LAG-3 antibody comprising heavy chains and Petition 870260055013, dated 08 / 06 / 2026, p. 129 / 490 (a) an anti-PD-1 antibody comprising 124 / 189 light chains comprising the sequences shown in SEQ ID Nos. 44 and 46, respectively, and (b) an anti-PD-1 antibody comprising heavy and light chains comprising the sequences shown in SEQ ID Nos. 57 and 58, respectively.

[00439] A method of treating a human individual afflicted with lung cancer is provided herein, the method comprising administering to the individual: (a) an anti-LAG-3 antibody, and (b) an anti-PD-1 antibody.

[00440] In some aspects, the method also involves administering a PDCT to the individual.

[00441] A method of treating a human individual with Stage IV or recurrent NSCLC who has a squamous histology is provided in this document, the method comprising administering to the individual: (a) an anti-LAG-3 antibody, (b) an anti-PD-1 antibody, and (c) a PDCT.

[00442] A method of treating a human individual with Stage IV or recurrent NSCLC who has a non-squamous histology is provided in this document, the method comprising administering to the individual: (a) an anti-LAG-3 antibody, (b) an anti-LAG-3 PD-1 antibody and (c) a PDCT.

[00443] Anti-LAG-3 antibodies and anti-PD-1 antibodies can be administered at any of the doses or dose combinations described herein.

[00444] In some respects, the dose of anti-LAG-3 antibody is 80 mg.

[00445] In some respects, the dose of anti-LAG-3 antibody is 160 mg.

[00446] In some respects, the dose of anti-LAG-3 antibody is 360 mg.

[00447] In some respects, the dose of anti-LAG-3 antibody is Petition 870260055013, dated 08 / 06 / 2026, p. 130 / 490 125 / 189 480 mg.

[00448] In some respects, the dose of anti-LAG-3 antibody is 720 mg.

[00449] In some respects, the dose of anti-LAG-3 antibody is 800 mg.

[00450] In some respects, the dose of anti-LAG-3 antibody is 960 mg.

[00451] In some aspects, the dose of anti-PD-1 antibody is 200 mg.

[00452] In some aspects, the dose of anti-PD-1 antibody is 240 mg.

[00453] In some aspects, the dose of anti-PD-1 antibody is 360 mg.

[00454] In some aspects, the dose of anti-PD-1 antibody is 480 mg.

[00455] In some respects, the dose of anti-LAG-3 antibody is 80 mg and the dose of anti-PD-1 antibody is 240 mg.

[00456] In some respects, the dose of anti-LAG-3 antibody is 160 mg and the dose of anti-PD-1 antibody is 480 mg.

[00457] In some respects, the dose of anti-LAG-3 antibody is 360 mg and the dose of anti-PD-1 antibody is 360 mg.

[00458] In some respects, the dose of anti-LAG-3 antibody is 480 mg and the dose of anti-PD-1 antibody is 480 mg.

[00459] In some respects, the dose of anti-LAG-3 antibody is 720 mg and the dose of anti-PD-1 antibody is 360 mg.

[00460] In some respects, the dose of anti-LAG-3 antibody is 800 mg and the dose of anti-PD-1 antibody is 200 mg.

[00461] In some respects, the dose of anti-LAG-3 antibody is 960 mg and the dose of anti-PD-1 antibody is 480 mg.

[00462] A method for processing is provided in this document. Petition 870260055013, dated 08 / 06 / 2026, page 131 / 490 126 / 189 treatment of a human individual with lung cancer, the method comprising administering to the individual: (a) a dose of approximately 360 mg of an anti-LAG-3 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable chain region heavy domains with the sequence presented in SEQ ID No:3 and CDR1, CDR2 and CDR3 domains of the variable chain region light with the sequence presented in SEQ ID No:4 and (b) a dose of approximately 360 mg of an anti-PD-1 antibody comprising CDR1, CDR2 and CDR3 domains of the variable chain region heavy with the sequence presented in SEQ ID No:13 and CDR1, CDR2 and CDR3 domains of the variable chain region light with the sequence defined in SEQ ID No:14.

[00463] A method of treating a human individual with lung cancer is provided herein, the method comprising administering to the individual: (a) a dose of approximately 720 mg of an anti-LAG-3 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable chain region heavy domains with the sequence presented in SEQ ID No:3 and the CDR1, CDR2 and CDR3 domains of the variable chain region light with the sequence presented in SEQ ID No:4, (b) a dose of approximately 360 mg of an anti-PD-1 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable chain region heavy with the sequence presented in SEQ ID No:13 and the CDR1, CDR2 and CDR3 domains of the variable chain region light with the sequence presented in SEQ ID No:14.

[00464] A method for treating a human individual with Stage IV or recurrent NSCLC who has squamous histology is provided in this document, the method comprising administering to the individual: (a) a dose of approximately 360 mg of an anti-LAG-3 antibody comprising CDR1, CDR2 and CDR3 domains of the variable region of the heavy chain with the sequence presented in SEQ ID Petition 870260055013, dated 08 / 06 / 2026, page 132 / 490 127 / 189 No. 3, and CDR1, CDR2 and CDR3 domains of the variable region of the light chain with the sequence presented in SEQ ID No. 4, (b) a dose of approximately 360 mg of an anti-PD-1 antibody comprising CDR1, CDR2 and CDR3 domains of the variable region of the heavy chain with the sequence presented in SEQ ID No. 13 and CDR1, CDR2 and CDR3 domains of the variable region of the light chain with the sequence presented in SEQ ID No. 14, (c) a PDCT comprising: (i) a dose of carboplatin to a target area under the concentration-time curve of approximately 6 mg / mL·min, and (ii) a dose of approximately 200 mg / m2 of paclitaxel, wherein the method is a first-line therapy.

[00465] A method for treating a human individual with Stage IV or recurrent NSCLC who has squamous histology is provided in this document, the method comprising administering to the individual: (a) a dose of approximately 720 mg of an anti-LAG-3 antibody comprising CDR1, CDR2 and CDR3 domains of the variable region of the heavy chain with the sequence presented in SEQ ID No.:3, and CDR1, CDR2 and CDR3 domains of the variable region of the light chain with the sequence presented in SEQ ID No.:4, (b) a dose of approximately 360 mg of an anti-PD-1 antibody comprising CDR1, CDR2 and CDR3 domains of the variable region of the heavy chain with the sequence presented in SEQ ID No.:13 and CDR1, CDR2 and CDR3 domains of the variable region of the light chain with the sequence presented in SEQ ID No.:14, (c) a PDCT comprising: (i) a dose of carboplatin for an area (i) a target under the concentration-time curve of approximately 6 mg / mL*min, and (ii) a dose of approximately 200 mg / m2 of paclitaxel,where the method is a first-line therapy.

[00466] A method of treating a human individual with Stage IV or recurrent NSCLC who has squamous histology is provided in this document, the method comprising administering to the individual: (a) a dose of approximately 360 mg of an antibody Petition 870260055013, dated 08 / 06 / 2026, p. 133 / 490 128 / 189 anti-LAG-3 comprising CDR1, CDR2 and CDR3 domains of the variable region of the heavy chain with the sequence presented in SEQ ID No.:3, and CDR1, CDR2 and CDR3 domains of the variable region of the light chain with the sequence presented in SEQ ID No.:4, (b) a dose of approximately 360 mg of an anti-PD-1 antibody comprising CDR1, CDR2 and CDR3 domains of the variable region of the heavy chain with the sequence presented in SEQ ID No.:13 and CDR1, CDR2 and CDR3 domains of the variable region of the light chain with the sequence presented in SEQ ID No.:14, (c) a PDCT comprising: (i) a dose of carboplatin to a target area under the concentration-time curve of approximately 6 mg / mL·min, and (ii) a dose of approximately 100 mg / m² of albumin-bound paclitaxel, wherein the method is a therapy Top-notch.

[00467] A method for treating a human individual with Stage IV or recurrent NSCLC who has squamous histology is provided in this document, the method comprising administering to the individual: (a) a dose of approximately 720 mg of an anti-LAG-3 antibody comprising CDR1, CDR2 and CDR3 domains of the variable region of the heavy chain with the sequence presented in SEQ ID No.:3, and CDR1, CDR2 and CDR3 domains of the variable region of the light chain with the sequence presented in SEQ ID No.:4, (b) a dose of approximately 360 mg of an anti-PD-1 antibody comprising CDR1, CDR2 and CDR3 domains of the variable region of the heavy chain with the sequence presented in SEQ ID No.:13 and CDR1, CDR2 and CDR3 domains of the variable region of the light chain with the sequence presented in SEQ ID No.:14, (c) a PDCT comprising: (i) a dose of carboplatin for an area (i) a target under the concentration-time curve of approximately 6 mg / mL·min, and (ii) a dose of approximately 100 mg / m2 of albumin-bound paclitaxel,where the method is a first-line therapy. Petition 870260055013, dated 08 / 06 / 2026, page 134 / 490 129 / 189

[00468] A method for treating a human individual with Stage IV or recurrent NSCLC having a non-squamous histology is provided in this document, the method comprising administering to the individual: (a) a dose of approximately 360 mg of an anti-LAG-3 antibody comprising CDR1, CDR2, and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No. 3 and CDR1, CDR2, and CDR3 domains of the variable light chain region with the sequence presented in SEQ ID No. 4, (b) a dose of approximately 360 mg of an anti-PD-1 antibody comprising CDR1, CDR2, and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No. 13 and CDR1, CDR2, and CDR3 domains of the variable light chain region having the sequence presented in SEQ ID No. 14, (c) a PDCT comprising: (i) a dose of carboplatin for an area (i) a target under the concentration-time curve of approximately 5 mg / mL^min or approximately 6 mg / mL^min, and (ii) a dose of approximately 500 mg / m2 of pemetrexed,where the method is a first-line therapy.

[00469] A method for treating a human individual with Stage IV or recurrent NSCLC having a non-squamous histology is provided in this document, the method comprising administering to the individual: (a) a dose of approximately 720 mg of an anti-LAG-3 antibody comprising CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No:3 and CDR1, CDR2 and CDR3 domains of the variable light chain region with the sequence presented in SEQ ID No:4, (b) a dose of approximately 360 mg of an anti-PD-1 antibody comprising CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No:13 and CDR1, CDR2 and CDR3 domains of the variable light chain region having the sequence presented in SEQ ID No:14, (c) a PDCT comprising: (i) a Petition 870260055013, dated 08 / 06 / 2026, page 135 / 490 130 / 189 dose of carboplatin to a target area under the concentration-time curve of approximately 5 mg / mL^min or approximately 6 mg / mL^min, and (ii) a dose of approximately 500 mg / m2 of pemetrexed, wherein the method is a first-line therapy.

[00470] A method for treating a human individual with Stage IV or recurrent NSCLC who has a non-squamous histology is provided in this document, the method comprising administering to the individual: (a) a dose of approximately 360 mg of an anti-LAG-3 antibody comprising CDR1, CDR2, and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No. 3 and CDR1, CDR2, and CDR3 domains of the variable light chain region with the sequence presented in SEQ ID No. 4, (b) a dose of approximately 360 mg of an anti-PD-1 antibody comprising CDR1, CDR2, and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No. 13 and CDR1, CDR2, and CDR3 domains of the variable light chain region having the sequence presented in SEQ ID No. 14, (c) a PDCT comprising: (i) a dose of approximately 75 mg / m2 of cisplatin(ii) a dose of approximately 500 mg / m2 of pemetrexed, wherein the method is a first-line therapy.

[00471] A method for treating a human individual with Stage IV or recurrent NSCLC who has a non-squamous histology is provided in this document, the method comprising administering to the individual: (a) a dose of approximately 720 mg of an anti-LAG-3 antibody comprising CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No:3 and CDR1, CDR2 and CDR3 domains of the variable light chain region with the sequence presented in SEQ ID No:4, (b) a dose of approximately 360 mg of an anti-PD-1 antibody comprising the CDR1, CDR2 and CDR3 domains of the variable heavy chain region Petition 870260055013, dated 08 / 06 / 2026, page 136 / 490 131 / 189 with the sequence presented in SEQ ID No:13 and CDR1, CDR2, and CDR3 domains of the variable light chain region with the sequence presented in SEQ ID No:14, (c) a PDCT comprising: (i) a dose of approximately 75 mg / m2 of cisplatin and (ii) a dose of approximately 500 mg / m2 of pemetrexed, wherein the method is a first-line therapy.

[00472] In some respects, the anti-LAG-3 antibody and the anti-PD-1 antibody are administered approximately once every three weeks. In some respects, the anti-LAG-3 antibody and the anti-PD-1 antibody are administered on Day 1 of each three-week cycle.

[00473] In some aspects, the anti-LAG-3 antibody is administered intravenously over approximately 30 minutes.

[00474] In some aspects, the anti-PD-1 antibody is administered intravenously over approximately 30 minutes.

[00475] In some respects, the composition comprising an anti-LAG-3 antibody and an anti-PD-1 antibody is administered intravenously over approximately 30 minutes.

[00476] In some respects, the anti-LAG-3 antibody and the anti-PD-1 antibody are administered intravenously from a single intravenous bag over approximately 30 minutes.

[00477] In some respects, PDCT is administered every three weeks. In some respects, PDCT is administered in a three-week cycle for up to about 4 cycles.

[00478] In some respects, anti-LAG-3 antibody and anti-PD-1 antibody are administered prior to a PDCT.

[00479] In some respects, PDCT comprises carboplatin and paclitaxel. In some respects, paclitaxel is administered over approximately 180 minutes on Day 1 of each cycle followed by intravenously administered carboplatin over approximately 30 minutes on Day 1 of each cycle. In some respects, NSCLC has a squamous histology. Petition 870260055013, dated 08 / 06 / 2026, p. 137 / 490 132 / 189

[00480] In some respects, PDCT comprises carboplatin and albumin-bound paclitaxel. In some respects, albumin-bound paclitaxel is administered over approximately 30 minutes on days 1, 8, and 15 of each cycle followed by intravenously administered carboplatin over approximately 30 minutes on day 1 of each cycle. In some respects, NSCLC has a squamous histology.

[00481] In some aspects, PDCT comprises carboplatin and pemetrexed. In some aspects, pemetrexed is administered over approximately 10 minutes on Day 1 of each cycle, followed by carboplatin administered intravenously over approximately 30 minutes on Day 1 of each cycle. In some aspects, pemetrexed is administered at a maintenance dose alone or in combination with anti-LAG-3 and anti-PD-1 antibodies in individuals who have stable disease or a response after PDCT administration for approximately 4 three-week cycles. In some aspects, the maintenance dose of pemetrexed is 500 mg / m2. In some aspects, the maintenance dose is administered on Day 1 of a three-week cycle. In some aspects, the maintenance dose continues until disease progression or unacceptable toxicity. In some aspects, NSCLC has a non-squamous histology.

[00482] In some respects, PDCT comprises cisplatin and pemetrexed. In some respects, pemetrexed is administered over approximately 10 minutes on Day 1 of each cycle, followed by cisplatin administered intravenously over approximately 30 minutes on Day 1 of each cycle. In some respects, pemetrexed is administered at a maintenance dose alone or in combination with anti-LAG-3 and anti-PD-1 antibodies in individuals who have stable disease or a response after PDCT administration for approximately 4 cycles. In some respects, the maintenance dose of pemetrexed is 500 mg / m2. In some respects, the maintenance dose is administered on Day 1 of Petition 870260055013, dated 08 / 06 / 2026, p. 138 / 490 133 / 189 a three-week cycle. In some respects, the maintenance dose continues until disease progression or unacceptable toxicity. In some respects, NSCLC has a non-squamous histology. II.B.3. a.ii. Anti-PD-L1 Antibodies

[00483] Anti-PD-L1 antibodies known in the art can be used in the methods of the invention. Examples of anti-PD-L1 antibodies useful in the compositions and methods of the present invention include the antibodies described in U.S. Patent No. 9,580,507. Human anti-PD-L1 monoclonal antibodies described in U.S. Patent No. 9,580,507 have been shown to exhibit one or more of the following characteristics: (a) bind to human PD-L1 with a Kd of 1 x 10-7M or less, as determined by surface plasmon resonance using a Biacore biosensor system; (b) increase T cell proliferation in a lymphocyte mixed reaction (MLR) assay; (c) increase interferon-γ production in an MLR assay; (d) increase IL-2 secretion in an MLR assay; (e) stimulate antibody responses; and (f) reverse the effect of regulatory T cells on effector T cells and / or dendritic cells.The anti-PD-L1 antibodies usable in the present invention include monoclonal antibodies that bind specifically to human PD-L1 and exhibit at least one, and in some respects at least five, of the preceding characteristics.

[00484] Anti-PD-L1 antibodies that can be used in the methods of the invention include BMS-936559 (also known as 12A4, MDX-1105; see, for example, U.S. Patent No. 7,943,743 and WO 2013 / 173223), atezolizumab (Roche; also known as TECENTRIQ®; MPDL3280A, RG7446; see US 8,217,149; see also Herbst et al. (2013) J Clin Oncol 31(suppl): 3000), durvalumab (AstraZeneca; also known as IMFINZI™, MEDI-4736; see WO 2011 / 066389), avelumab (Pfizer; also known as BA Petition 870260055013, dated 08 / 06 / 2026, page 139 / 490 134 / 189 VENCIO®, MSB-0010718C; see, WO 2013 / 079174), STI-1014 (Sorrento; see, WO2013 / 181634), CX-072 (Cytomx; see, WO2016 / 149201), KN035 (3D Med / Alphamabe; see, Zhang et al., Cell Discov. 7: 3 (March 2017), LY3300054 (Eli Lilly Co.; see, for example, WO 2017 / 034916), BGB-A333 (BeiGene; see, Desai et al., JCO 36 (15suppl): TPS3113 (2018)), ICO 36, FAZ053 (Novartis) and CK301 (Checkpoint Therapeutics; see, Gorelik et al., AACR: Abstract 4606 (April 2016)).

[00485] The anti-PD-L1 antibodies that can be used in the methods of the invention also include isolated antibodies that specifically bind to human PD-L1 and cross-compete for binding to human PD-L1 with any anti-PD-L1 antibody described herein, for example, atezolizumab, durvalumab and / or avelumab. In some respects, the anti-PD-L1 antibody binds to the same epitope as any of the anti-PD-L1 antibodies described herein, for example, atezolizumab, durvalumab and / or avelumab. In certain respects, the antibodies that cross-compete for binding to human PD-L1 or bind to the same epitope region as any anti-PD-L1 antibody described herein, for example, atezolizumab, durvalumab and / or avelumab, are monoclonal antibodies. For administration to humans, these cross-competing antibodies are chimeric antibodies, modified antibodies, or humanized / human antibodies.Such chimeric, modified, humanized, or human monoclonal antibodies can be prepared and isolated by methods well known in the art.

[00486] The anti-PD-L1 antibodies that can be used in the methods of the invention also include antigen-binding moieties of any of the above full-size antibodies.

[00487] The anti-PD-L1 antibodies that can be used in the methods of the invention are antibodies that bind to PD-L1 with high specificity. Petition 870260055013, dated 08 / 06 / 2026, p. 140 / 490 135 / 189 efficacy and affinity, block PD-1 binding and inhibit the immunosuppressive effect of the PD-1 signaling pathway. In any of the compositions or methods described herein, an anti-PD-L1 antibody includes an antigen-binding portion or fragment that binds to PD-L1 and exhibits functional properties similar to those of whole antibodies in inhibiting receptor binding and upregulating the immune system. In certain respects, the anti-PD-L1 antibody or its antigen-binding portion cross-competes with atezolizumab, durvalumab, and / or avelumab for binding to human PD-L1.

[00488] In some respects, an anti-PD-L1 antibody is replaced by an anti-PD-1 antibody in any of the methods described herein.

[00489] In some respects, the anti-PD-L1 antibody is a natural-sized antibody.

[00490] In some respects, the anti-PD-L1 antibody is a monoclonal, human, humanized, chimeric, or multispecific antibody. In some respects, the multispecific antibody is a DART, a DVD-Ig, or a bispecific antibody.

[00491] In some respects, the anti-PD-L1 antibody is an F(ab')2 fragment, a Fab' fragment, a Fab fragment, an Fv fragment, an scFv fragment, a dsFv fragment, a dAb fragment, or a single-chain binding polypeptide.

[00492] In some respects, the anti-PD-L1 antibody is BMS936559, atezolizumab, durvalumab, avelumab, STI-1014, CX-072, KN035, LY3300054, BGB-A333, ICO 36, FAZ053, CK-301 or comprises its antigen-binding moiety.

[00493] In some respects, the PD-L1 antibody is atezolizumab. Atezolizumab is a fully humanized anti-PD-L1 IgG1 monoclonal antibody. In some respects, atezolizumab is administered as a flat dose of approximately 800 mg once every two weeks. Petition 870260055013, dated 08 / 06 / 2026, p. 141 / 490 136 / 189 manas. In some respects, atezolizumab is administered as a flat dose of approximately 840 mg once every two weeks.

[00494] In some respects, atezolizumab is administered intravenously at a dose of approximately 1,200 mg on Day 1 of a three-week cycle.

[00495] In some respects, atezolizumab is administered intravenously at a dose of approximately 1,200 mg on Day 1 of a three-week cycle, and bevacizumab is administered at a dose of approximately 15 mg / kg on Day 1 of each cycle.

[00496] In some respects, atezolizumab is administered intravenously at a dose of about 1,200 mg on Day 1 of a three-week cycle for about 4 to about 6 cycles, bevacizumab is administered at a dose of about 15 mg / kg on Day 1 of each cycle, paclitaxel is administered intravenously at a dose of about 200 mg / m2 over about 180 minutes on Day 1 of each cycle, and carboplatin is administered intravenously over about 30 minutes at a dose to a target AUC of about 6 mg / mL •min on Day 1 of each cycle.

[00497] In some respects, the PD-L1 antibody is durvalumab. Durvalumab is a human IgG1 monoclonal antibody that protects against PD-L1. In some respects, durvalumab is administered at a dose of approximately 10 mg / kg once every two weeks. In some respects, durvalumab is administered as a flat dose of approximately 800 mg / kg once every two weeks. In some respects, durvalumab is administered at a dose of approximately 10 mg / kg once every two weeks for up to 12 months. In some respects, durvalumab is administered as a flat dose of approximately 800 mg / kg once every two weeks. In some respects, durvalumab is administered as a flat dose of approximately 1200 mg / kg once every 3 weeks. Petition 870260055013, dated 08 / 06 / 2026, page 142 / 490 137 / 189

[00498] In some respects, the PD-L1 antibody is avelumab. Avelumab is a human IgG1 lambda anti-PD-L1 monoclonal antibody. In some respects, avelumab is administered as a flat dose of approximately 800 mg once every two weeks. II.B.3. b. CTLA-4 inhibitors

[00499] In some respects, the checkpoint inhibitor described herein includes a CTLA-4 inhibitor. In some respects, the CTLA-4 inhibitor is an anti-CTLA-4 antibody.

[00500] The anti-CTLA-4 antibodies that can be used in the methods of the invention bind to human CTLA-4 and disrupt the interaction of CTLA-4 with a human B7 receptor. Since the interaction of CTLA-4 with B7 transduces a signal that leads to the inactivation of CTLA-4 receptor-bearing T cells, disrupting the interaction effectively induces, enhances, or prolongs the activation of such T cells, thus inducing, enhancing, or prolonging an immune response.

[00501] Human monoclonal antibodies that specifically bind to CTLA-4 with high affinity have been described in U.S. Patents Nos. 6,984,720. Other anti-CTLA-4 monoclonal antibodies have been described, for example, in U.S. Patents Nos. 5,977,318, 6,051,227, 6,682,736 and 7,034,121 and International Publications Nos. WO 2012 / 122444, WO 2007 / 113648, WO 2016 / 196237 and WO 2000 / 037504, each of which is incorporated herein by reference in its entirety. The human anti-CTLA-4 monoclonal antibodies described in U.S. Patent No. 6,984,720 has demonstrated to exhibit one or more of the following characteristics: (a) binds specifically to human CTLA-4 with a binding affinity reflected by an equilibrium association constant (Ka) of at least about 10⁷M⁻¹, or about 10⁹M⁻¹, or about 10¹⁰M⁻¹ to 10¹¹M⁻¹ or higher, as determined by Biacore analysis; (b) a kinetic association constant (ka) of at least about 10³, about Petition 870260055013, dated 08 / 06 / 2026, p. 143 / 490 138 / 189 104 or about 105 m-1 s⁻¹; (c) a kinetic dissociation constant (kd) of at least about 10³, about 10⁴ or about 10⁵ m⁻¹ s⁻¹; and (d) inhibits the binding of CTLA-4 to B7-1 (CD80) and B7-2 (CD86). Useful anti-CTLA-4 antibodies for the present invention include monoclonal antibodies that specifically bind to human CTLA-4 and exhibit at least one, at least two, or at least three of the preceding features.

[00502] Anti-CTLA-4 antibodies that can be used in the methods of the invention include ipilimumab (also known as YERVOY®, MDX-010, 10D1; see U.S. Patent No. 6,984,720), MK-1308 (Merck), AGEN-1884 (Agenus Inc.; see WO 2016 / 196237) and tremelimumab (AstraZeneca; also known as ticilimumab, CP-675,206; see WO 2000 / 037504 and Ribas, Update Cancer Ther. 2(3): 133-39 (2007)).

[00503] In some respects, the anti-CTLA-4 antibody binds specifically to human CTLA-4 and cross-competes for binding to human CTLA-4 with any anti-CTLA-4 antibody described herein, for example, ipilimumab and / or tremelimumab. In some respects, the anti-CTLA-4 antibody binds to the same epitope as any of the anti-CTLA-4 antibodies described herein, for example, ipilimumab and / or tremelimumab.

[00504] In some respects, antibodies that cross-compete for binding to human CTLA-4 or bind to the same epitope region as any anti-CTLA-4 antibody described herein, for example, ipilimumab and / or tremelimumab, are monoclonal antibodies. For administration to humans, these cross-competing antibodies are chimeric antibodies, modified antibodies, or humanized or human antibodies.

[00505] Anti-CTLA-4 antibodies that can be used in the methods of the invention also include antigen-binding moieties of Petition 870260055013, dated 08 / 06 / 2026, page 144 / 490 139 / 189 any of the above complete antibodies.

[00506] In some respects, the anti-CTLA-4 antibody is a full-size antibody. In some respects, the anti-CTLA-4 antibody is a monoclonal, human, humanized, chimeric, or multispecific antibody. In some respects, the multispecific antibody is a DART, a DVD-Ig, or a bispecific antibody.

[00507] In some respects, the anti-CTLA-4 antibody is an F(ab')2 fragment, a Fab' fragment, a Fab fragment, an Fv fragment, an scFv fragment, a dsFv fragment, a dAb fragment, or a single-chain binding polypeptide.

[00508] In some respects, the anti-CTLA-4 antibody is ipilimumab, tremelimumab, MK-1308, AGEN-1884 or comprises an antigen-binding moiety thereof.

[00509] In some respects, the anti-CTLA-4 antibody is ipilimumab. Ipilimumab is a fully human IgG1 monoclonal antibody that blocks the binding of CTLA-4 to its B7 ligands, thereby stimulating T cell activation. In some respects, ipilimumab is administered at a dose of approximately 3 mg / kg once every 3 weeks. In some respects, ipilimumab is administered at a dose of approximately 10 mg / kg once every 3 weeks. In some respects, ipilimumab is administered at a dose of approximately 10 mg / kg once every 12 weeks. In some respects, ipilimumab is administered in four doses. In some respects, ipilimumab is administered on Day 1 of each cycle. II.B.4. Therapies for Sensitization Mutations

[00510] In some aspects, a method of the invention comprises treating an individual with a therapy-sensitive mutation with targeted inhibitors, such as a sensitizing mutation in a gene like EGFR, ALK, ROS-1, NTRK, or BRAF. Such methods may further comprise administering a targeted inhibitor. Petition 870260055013, dated 08 / 06 / 2026, page 145 / 490 140 / 189 of the mutated genes, including standard treatment therapies for individuals with such mutations who suffer from NSCLC.

[00511] In some respects, a method of the invention comprises a first-line therapy for an individual with advanced or metastatic NSCLC who has an EGFR sensitizing mutation, comprising administering to the individual afatinib (e.g., 40 mg orally once daily), erlotinib (e.g., 150 mg orally once daily), dacomitinib (e.g., 45 mg orally once daily), gefitinib (e.g., 250 mg orally once daily) or osimertinib (e.g., 80 mg orally once daily).

[00512] EGFR sensitizing, comprising administering afatinib and cetuximab to the individual (e.g., 40 mg of afatinib orally once daily on Days 1-14 and cetuximab at 500 mg / m2 on Day 1 in 2-week cycles) or osimertinib (e.g., 80 mg orally once daily).

[00513] In some respects, a method of the invention comprises a first-, second-, or third-line therapy for an individual with advanced or metastatic NSCLC who has a sensitizing ALK mutation (e.g., ALK rearrangement), comprising administering to the individual alectinib (e.g., 600 mg orally twice daily), brigatinib (e.g., a 4-week cycle of 90 mg orally once daily on days 1-7, 180 mg orally once daily on days 8-28 followed by 180 mg orally once daily on days 29-56), ceritinib (e.g., 450 mg orally once daily), or crizotinib (e.g., 250 mg orally twice daily).

[00514] In some respects, a method of the invention comprises a second- or third-line therapy for an individual with advanced or metastatic NSCLC who has a sensitizing ALK mutation (by Petition 870260055013, dated 08 / 06 / 2026, p. 146 / 490 141 / 189 example, ALK rearrangement), comprising administering lorlatinib to the individual (e.g., 100 mg orally once daily).

[00515] ROS-1 sensitizing mutation (e.g., ROS-1 rearrangement), comprising administering ceritinib (e.g., 450 mg orally once daily), crizotinib (e.g., 250 mg orally twice daily), or entrectinib (e.g., 600 mg orally once daily) to the individual. In some respects, a method of the invention comprises a second- or third-line treatment pattern for an individual with advanced or metastatic NSCLC who has a ROS-1 sensitizing mutation (e.g., ROS-1 rearrangement), wherein the treatment pattern comprises administering lorlatinib (e.g., 100 mg orally once daily) to the individual.

[00516] BRAF sensitizing mutation (e.g., BRAF V600E), comprising administering to the individual dabrafenib (e.g., 150 mg orally twice daily), dabrafenib and trametinib (e.g., 150 mg orally twice daily and 2 mg orally once daily trametinib) or vemurafenib (e.g., 960 mg orally once daily).

[00517] NTRK sensitizing mutation (e.g., NTRK gene fusion), comprising administering entrectinib (e.g., 600 mg orally once daily) or larotrectinib (e.g., 100 mg orally twice daily) to the individual. III. Pharmaceutical Compositions

[00518] The therapeutic agents of the present invention may be constituted in a composition, for example, a pharmaceutical composition containing an inhibitor, antibody and / or agent as described herein and a pharmaceutically acceptable carrier. When used herein, a pharmaceutically acceptable carrier includes any and all solvents, media Petition 870260055013, dated 08 / 06 / 2026, page 147 / 490 142 / 189 of dispersion, coatings, antibacterial and antifungal agents, isotonic agents and absorption retardants and the like that are physiologically compatible.

[00519] In some respects, the carrier for a composition containing an inhibitor, antibody and / or agent as described herein is suitable for intravenous, intramuscular, subcutaneous, parenteral, spinal or epidermal administration (e.g., by injection or infusion). In some respects, the carrier is suitable for non-parenteral administration, e.g., oral. In some respects, subcutaneous injection is based on the ENHANZE® drug delivery technology of Halozyme Therapeutics (see U.S. Patent No. 7,767,429, which is incorporated herein by reference in its entirety). ENHANZE® uses a co-formulation of an antibody with recombinant human hyaluronidase enzyme (rHuPH20), which removes traditional limitations on the volume of biological products and drugs that can be administered subcutaneously due to the extracellular matrix (see U.S. Patent No. 7,767,429).A pharmaceutical composition of the invention may include one or more pharmaceutically acceptable salts, antioxidants, aqueous and non-aqueous carriers and / or adjuvants, such as preservatives, humectants, emulsifying agents and dispersing agents. In some respects, the pharmaceutical composition for the present invention may also comprise recombinant human hyaluronidase enzyme, for example, rHuPH20.

[00520] Treatment is continued as long as clinical benefit is observed or until unacceptable toxicity or disease progression occurs. Dosage and frequency vary depending on the half-life of the inhibitor, antibody, and / or agent in the individual. In general, human antibodies have the longest half-life, followed by humanized antibodies, chimeric antibodies, and non-human antibodies. A Petition 870260055013, dated 08 / 06 / 2026, page 148 / 490 143 / 189 Dosage and frequency of administration may vary depending on whether the treatment is prophylactic or therapeutic. In prophylactic applications, a relatively low dosage is typically administered at relatively infrequent intervals over a long period of time. Some patients continue to receive treatment for the rest of their lives. In therapeutic applications, a relatively high dosage at relatively short intervals is sometimes necessary until disease progression is reduced or terminated, and preferably until the patient shows partial or complete improvement of disease symptoms. After that, the patient may receive a prophylactic regimen.

[00521] The actual dosage levels of the active ingredients (i.e., inhibitors, antibodies, and / or agents) in the pharmaceutical compositions of the present invention may be varied in order to obtain an amount of the active ingredient that is effective in achieving the desired therapeutic response for a given patient, composition, and route of administration, without being unduly toxic to the patient. The dosage level selected will depend on a variety of pharmacokinetic factors, including the activity of the particular compositions of the present invention employed, the route of administration, the time of administration, the excretion rate of the specific compound being employed, the duration of treatment, other drugs, compounds, and / or materials used in combination with the particular compositions employed, the age, sex, weight, condition, general health, and previous medical history of the patient being treated, and similar factors well known in the medical art.A composition of the present invention can be administered via one or more routes of administration using one or more of a variety of methods well known in the art. As will be appreciated by those skilled in the art, the route and / or method of administration will vary depending on the... Petition 870260055013, dated 08 / 06 / 2026, page 149 / 490 144 / 189 desired results.

[00522] A pharmaceutical composition comprising an anti-LAG-3 antibody and an anti-PD-1 antibody as described herein is provided herein in any of the doses or dose combinations described herein.

[00523] In some respects, the pharmaceutical composition is for treating a human individual with lung cancer as described in this document.

[00524] In some respects, a method for treating a human individual with lung cancer as described herein includes the administration of a pharmaceutical composition as described herein.

[00525] In some respects, the pharmaceutical composition comprises a dose of relatlimab and a dose of an anti-PD-1 antibody as described herein. In some respects, the anti-PD-1 antibody is nivolumab, pembrolizumab, cemiplimab or espartalizumab. In some respects, the anti-PD-1 antibody is nivolumab.

[00526] In some respects, the pharmaceutical composition comprises a dose of favezelimab and a dose of an anti-PD1 antibody as described herein. In some respects, the anti-PD-1 antibody is nivolumab, pembrolizumab, cemiplimab or espartalizumab. In some respects, the anti-PD-1 antibody is pembrolizumab.

[00527] In some respects, the pharmaceutical composition comprises a dose of fianlimab and a dose of an anti-PD-1 antibody as described herein. In some respects, the anti-PD-1 antibody is nivolumab, pembrolizumab, cemiplimab or espartalizumab. In some respects, the anti-PD-1 antibody is cemiplimab. Petition 870260055013, dated 08 / 06 / 2026, page 150 / 490 145 / 189

[00528] In some respects, the pharmaceutical composition comprises a dose of ieramilimab and a dose of an anti-PD1 antibody as described herein. In some respects, the anti-PD-1 antibody is nivolumab, pembrolizumab, cemiplimab or espartalizumab. In some respects, the anti-PD-1 antibody is espartalizumab.

[00529] In some aspects, the pharmaceutical composition comprises an anti-LAG-3 antibody to anti-PD-1 antibody ratio of about 1:1, about 1:2, about 1:3, about 1:4, about 1:5, about 1:6, about 1:7, about 1:8, about 1:9, about 1:10, about 1:15, about 1:20, about 1:30, about 1:40, about 1:50, about 1:60, about 1:70, about 1:80, about 1:90, about 1:100, about 1:120, about 1:140, about 1:160, about 1:180, about 1:200, about 200:1, about 180:1, approximately 160:1, approximately 140:1, approximately 120:1, approximately 100:1, approximately 90:1, approximately 80:1, approximately 70:1, approximately 60:1, approximately 50:1, approximately 40:1, approximately 30:1, approximately 20:1, approximately 15:1, approximately 10:1, approximately 9:1, approximately 8:1, approximately 7:1, approximately 6:1, approximately 5:1, approximately 4:1, approximately 3:1 or approximately 2:1.

[00530] In some respects, the pharmaceutical composition comprises an anti-LAG-3 antibody to anti-PD-1 antibody ratio of approximately 1:3.

[00531] In some respects, the pharmaceutical composition comprises an anti-LAG-3 antibody to anti-PD-1 antibody ratio of approximately 1:1.

[00532] In some respects, the pharmaceutical composition comprises an anti-LAG-3 antibody to anti-PD-1 antibody ratio of approximately 2:1.

[00533] In some respects, the pharmaceutical composition comprises a ratio of anti-LAG-3 antibody to anti-PD-1 antibody of Petition 870260055013, dated 08 / 06 / 2026, page 151 / 490 146 / 189 approximately 4:1.

[00534] In some respects, the total amount of anti-LAG-3 and anti-PD-1 antibodies in the pharmaceutical composition is approximately 20 mg / mL, approximately 25 mg / mL, approximately 30 mg / mL, approximately 35 mg / mL, approximately 40 mg / mL, approximately 45 mg / mL, approximately 50 mg / mL, approximately 55 mg / mL, approximately 60 mg / mL, approximately 65 mg / mL, approximately 70 mg / mL, approximately 75 mg / mL, approximately 80 mg / mL, approximately 85 mg / mL, approximately 90 mg / mL, approximately 95 mg / mL, approximately 100 mg / mL, approximately 105 mg / mL, approximately 110 mg / mL, approximately 115 mg / mL, approximately 120 mg / mL, about 125 mg / mL, about 130 mg / mL, about 135 mg / mL, approximately 140 mg / mL, approximately 145 mg / mL, approximately 150 mg / mL, approximately 155 mg / mL, approximately 160 mg / mL, approximately 165 mg / mL, approximately 170 mg / mL, approximately 175 mg / mL, approximately 180 mg / mL, approximately 185 mg / mL, approximately 190 mg / mL, approximately 195 mg / mL, approximately 200 mg / mL, approximately 205 mg / mL, approximately 210 mg / mL, approximately 215 mg / mL, approximately 220 mg / mL, approximately 225 mg / mL, approximately 230 mg / mL, approximately 235 mg / mL, approximately 240 mg / mL, approximately 245 mg / mL, approximately 250 mg / mL, approximately 255 mg / mL, approximately 260 mg / mL, approximately 265 mg / mL, approximately 270 mg / mL, approximately 275 mg / mL, approximately 280 mg / mL, approximately 285 mg / mL, approximately 290 mg / mL, approximately 295 mg / mL, approximately 300 mg / mL, approximately 305 mg / mL, approximately 310 mg / mL, approximately 315 mg / mL, approximately 320 mg / mL, approximately 325 mg / mL, approximately 330 mg / mL, approximately 335 mg / mL, approximately 340 mg / mL, approximately 345 mg / mL, approximately 350 mg / mL, approximately 355 mg / mL, approximately 360 mg / mL, approximately 365 mg / mL, approximately 370 mg / mL, approximately 375 mg / mL, approximately 380 mg / mL,about 385 mg / mL, about 390, mg / mL, about 395 mg / mL, about 400 mg / mL, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, about 110 mg, about 120 mg, about 130 Petition 870260055013, dated 08 / 06 / 2026, page 152 / 490 147 / 189 mg, approximately 140 mg, approximately 150 mg, approximately 160 mg, approximately 170 mg, approximately 180 mg, approximately 190 mg, approximately 200 mg, approximately 210 mg, approximately 220 mg, approximately 230 mg, approximately 240 mg, approximately 250 mg, approximately 260 mg, approximately 270 mg, approximately 280 mg, approximately 290 mg, approximately 300 mg, approximately 310 mg, approximately 320 mg, approximately 330 mg, approximately 340 mg, approximately 350 mg, approximately 360 mg, approximately 370 mg, approximately 380 mg, approximately 390 mg, approximately 400 mg, approximately 410 mg, approximately 420 mg, approximately 430 mg, approximately 440 mg, approximately 450 mg, approximately 460 mg, approximately 470 mg, approximately 480 mg, approximately 490 mg, approximately 500 mg, approximately 510 mg, approximately 520 mg, approximately 530 mg, approximately 540 mg, approximately 550 mg, approximately 560 mg, approximately 570 mg, approximately 580 mg, approximately 590 mg, approximately 600 mg, approximately 610 mg, approximately 620 mg, approximately 630 mg, approximately 640 mg, approximately 650 mg, approximately 660 mg, approximately 670 mg, approximately 680 mg, approximately 690 mg, approximately 700 mg, approximately 710 mgapproximately 720 mg, approximately 730 mg, approximately 740 mg, approximately 750 mg, approximately 760 mg, approximately 770 mg, approximately 780 mg, approximately 790 mg, approximately 800 mg, approximately 810 mg, approximately 820 mg, approximately 830 mg, approximately 840 mg, approximately 850 mg, approximately 860 mg, approximately 870 mg, approximately 880 mg, approximately 890 mg, approximately 900 mg, approximately 910 mg, approximately 920 mg, approximately 930 mg, approximately 940 mg, approximately 950 mg, approximately 960 mg, approximately 970 mg, approximately 980 mg, approximately 990 mg, approximately 1000 mg, approximately 1010 mg, approximately 1020 mg, approximately 1030 mg, approximately, 1040 mg, approximately 1050 mg, approximately 1060 mg, approximately 1070 mg, approximately 1080 mg, approximately 1090 mg, approximately 1100 mg, approximately 1110 mg, approximately 1120 mg, approximately 1130 mg, approximately 1140 mg, approximately 1150 mg, approximately 1160 mg, approximately 1170 mg, approximately 1180 mg, approximately 1190 mg, approximately 1200 mg, approximately 1210 mg, approximately 1220 mg, approximately 1230 mg, approximately 1240 mg, approximately Petition 870260055013, dated 08 / 06 / 2026, page 153 / 490 148 / 189 1250 mg, about 1260 mg, about 1270 mg, about 1280 mg, about 1290 mg, about 1300 mg, about 1310 mg, about 1320 mg, about 1330 mg, about 1340 mg, about 1350 mg, about 1360 mg, about 1370 mg, about 1380 mg, about 1390 mg, about 1400 mg, about 1410 mg, about 1420 mg, about 1430 mg, about 1440 mg, about 1450 mg, about 1460 mg, about 1470 mg, about 1480 mg, about 1490 mg, about 1500 mg, about 1510 mg, about 1520 mg, about 1530 mg, about 1540 mg, about 1550 mg, about 1560 mg, about 1570 mg, about 1580 mg, about 1590 mg, about 1600 mg, about 1610 mg, about 1620 mg, about 1630 mg, about 1640 mg, about 1650 mg, about 1660 mg, about 1670 mg, about 1680 mg, about 1690 mg, about 1700 mg, about 1710 mg, about 1720 mg, about 1730 mg, about 1740 mg, about 1750 mg, about 1760 mg, about 1770 mg or about 1780 mg.

[00535] In some respects, the total amount of anti-LAG-3 and anti-PD-1 antibodies in the pharmaceutical composition is approximately 25 mg / mL.

[00536] In some respects, the total amount of anti-LAG-3 and anti-PD-1 antibodies in the pharmaceutical composition is approximately 50 mg / mL.

[00537] In some respects, the total amount of anti-LAG-3 and anti-PD-1 antibodies in the pharmaceutical composition is approximately 150 mg / mL.

[00538] In some respects, the total amount of anti-LAG-3 and anti-PD-1 antibodies in the pharmaceutical composition is approximately 50 mg.

[00539] In some respects, the total amount of anti-LAG-3 and anti-PD-1 antibodies in the pharmaceutical composition is approximately 320 mg.

[00540] In some respects, the total amount of anti- Petition 870260055013, dated 08 / 06 / 2026, page 154 / 490 149 / 189 LAG-3 and anti-PD-1 antibodies in the pharmaceutical composition are approximately 640 mg.

[00541] In some respects, the total amount of anti-LAG-3 and anti-PD-1 antibodies in the pharmaceutical composition is approximately 720 mg.

[00542] In some respects, the total amount of anti-LAG-3 and anti-PD-1 antibodies in the pharmaceutical composition is approximately 960 mg.

[00543] In some respects, the total amount of anti-LAG-3 and anti-PD-1 antibodies in the pharmaceutical composition is approximately 1000 mg.

[00544] In some respects, the total amount of anti-LAG-3 and anti-PD-1 antibodies in the pharmaceutical composition is approximately 1,080 mg.

[00545] In some respects, the total amount of anti-LAG-3 and anti-PD-1 antibodies in the pharmaceutical composition is approximately 1440 mg.

[00546] In some aspects, the pharmaceutical composition includes approximately 10 mg / mL, approximately 12.5 mg / mL, approximately 15 mg / mL, approximately 17.5 mg / mL, approximately 20 mg / mL, approximately 22.5 mg / mL, approximately 25 mg / mL, approximately 27.5 mg / mL, approximately 30 mg / mL, approximately 32.5 mg / mL, approximately 35 mg / mL, approximately 37.5 mg / mL, approximately 40 mg / mL, approximately 42.5 mg / mL, approximately 45 mg / mL, approximately 47.5 mg / mL, approximately 50 mg / mL, approximately 55 mg / mL, approximately 60 mg / mL, approximately 65 mg / mL, approximately 70 mg / mL, approximately 75 mg / mL, about 80 mg / mL, about 85 mg / mL, about 90 mg / mL, about 95 mg / mL, about 100 mg / mL, about 105 mg / mL, about 110 mg / mL, about 115 mg / mL, about 120 mg / mL, about 125 mg / mL, 130 mg / mL, about 135 mg / mL, about 140 mg / mL, about 145 mg / mL, about 150 mg / mL, about 155 mg / mL, about 160 mg / mL, about 165 mg / mL, about 170 mg / mL, about 175 mg / mL, about 180 mg / mL, about 185 mg / mL, approximately 190 mg / mL, about 195 mg / mL, about 200 mg / mL, about 7 mg,approximately 21 mg, approximately, Petition 870260055013, dated 08 / 06 / 2026, page 155 / 490 150 / 189 mg, about 70 mg, about 80 mg, about 160 mg, about 200 mg, about 210 mg, about 300 mg, about 400 mg, about 480 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 960 mg, about 1000 mg, about 1100 mg, about 1200 mg or about 1300 mg of an anti-LAG-3 antibody.

[00547] In some aspects, the pharmaceutical composition comprises approximately 5 mg / mL, approximately 10 mg / mL, approximately 12.5 mg / mL, approximately 15 mg / mL, approximately 17.5 mg / mL, approximately 20 mg / mL, approximately 22.5 mg / mL, approximately 25 mg / mL, approximately 27.5 mg / mL, approximately 30 mg / mL, approximately 32.5 mg / mL, approximately 35 mg / mL, approximately 37.5 mg / mL, approximately 40 mg / mL, approximately 42.5 mg / mL, approximately 45 mg / mL, approximately 47.5 mg / mL, approximately 50 mg / mL, approximately 55 mg / mL, approximately 60 mg / mL, approximately 65 mg / mL, approximately 70 mg / mL, about 75 mg / mL, about 80 mg / mL, about 85 mg / mL, about 90 mg / mL, about 95 mg / mL, about 100 mg / mL, about 105 mg / mL, about 110 mg / mL, about 115 mg / mL, about 120 mg / mL, about 125 mg / mL, 130 mg / mL, about 135 mg / mL, about 140 mg / mL, about 145 mg / mL, about 150 mg / mL, about 155 mg / mL, about 160 mg / mL, about 165 mg / mL, about 170 mg / mL, about 175 mg / mL, about 180 mg / mL, about 185 mg / mL, about 190 mg / mL, about 195 mg / mL,about 200 mg / mL, about 40 mg, about 100 mg, about 200 mg, about 240 mg, about 300 mg, about 350 mg, about 360 mg, about 400 mg, or about 480 mg of an anti-PD-1 antibody.

[00548] In some respects, the pharmaceutical composition comprises approximately 12.5 mg / mL of an anti-LAG-3 antibody and approximately 37.5 mg / mL of an anti-PD-1 antibody.

[00549] In some respects, the pharmaceutical composition comprises approximately 20 mg / mL of an anti-LAG-3 antibody and approximately 5 Petition 870260055013, dated 08 / 06 / 2026, page 156 / 490 151 / 189 mg / mL of an anti-PD-1 antibody.

[00550] In some respects, the pharmaceutical composition comprises approximately 75 mg / mL of an anti-LAG-3 antibody and approximately 75 mg / mL of an anti-PD-1 antibody.

[00551] In some respects, the pharmaceutical composition comprises approximately 100 mg / mL of an anti-LAG-3 antibody and approximately 50 mg / mL of an anti-PD-1 antibody.

[00552] In some respects, the pharmaceutical composition comprises approximately 80 mg of an anti-LAG-3 antibody and approximately 240 mg of an anti-PD-1 antibody.

[00553] In some respects, the pharmaceutical composition comprises approximately 160 mg of an anti-LAG-3 antibody and approximately 480 mg of an anti-PD-1 antibody.

[00554] In some respects, the pharmaceutical composition comprises approximately 360 mg of an anti-LAG-3 antibody and approximately 360 mg of an anti-PD-1 antibody.

[00555] In some respects, the pharmaceutical composition comprises approximately 480 mg of an anti-LAG-3 antibody and approximately 480 mg of an anti-PD-1 antibody.

[00556] In some respects, the pharmaceutical composition comprises approximately 720 mg of an anti-LAG-3 antibody and approximately 360 mg of an anti-PD-1 antibody.

[00557] In some respects, the pharmaceutical composition comprises approximately 800 mg of an anti-LAG-3 antibody and approximately 200 mg of an anti-PD-1 antibody.

[00558] In some respects, the pharmaceutical composition comprises approximately 960 mg of an anti-LAG-3 antibody and approximately 480 mg of an anti-PD-1 antibody.

[00559] In some respects, the pharmaceutical composition comprises from about 5 mM to about 50 mM of histidine, from about 50 Petition 870260055013, dated 08 / 06 / 2026, p. 157 / 490 152 / 189 mM to about 300 mM of sucrose, from about 5 μM to about 1 mM of diethylenetriaminepentaacetic acid (DTPA) or ethylenediaminetetraacetic acid (EDTA), and from about 0.001% to about 1% (w / v) of polysorbate or poloxamer (e.g., polysorbate 80 (PS80), polysorbate 20 (PS20), poloxamer 188 (PX188), or any combination thereof).

[00560] In some respects, the pharmaceutical composition comprises approximately 20 mM of histidine, approximately 250 mM of sucrose, approximately 50 μM of DTPA and 0.05% of PS80.

[00561] In some aspects, the pH of the pharmaceutical composition is about 5 to about 6.5. In some aspects, the pH is about 5.3 to about 6.3. In some aspects, the pH is 5.8. In some aspects, the pH is 5.7.

[00562] An intravenous vial, syringe or bag comprising a pharmaceutical composition as described herein is provided in this document. In some respects, the invention includes an autoinjector comprising a pharmaceutical composition described herein.

[00563] In some respects, a bottle comprises a pharmaceutical composition as described in this document and the bottle further comprises a stopper and a seal. In some respects, the total volume in the bottle is about 5 mL, about 6 mL, about 7 mL, about 8 mL, about 9 mL, about 10 mL, about 11 mL, about 12 mL, about 13 mL, about 14 mL, about 15 mL, about 16 mL, about 17 mL, about 18 mL, about 19 mL or about 20 mL. IV. Kits

[00564] Also within the scope of the present invention are kits for treating a human individual with lung cancer comprising any of the antibodies, therapeutic agents and / or therapies Petition 870260055013, dated 08 / 06 / 2026, page 158 / 490 153 / 189 anticancer drugs described here.

[00565] Kits generally include a label indicating the intended use of the kit's contents and instructions for use. The term label includes any writing or engraved material provided on or with the kit, or that otherwise accompanies the kit.

[00566] A kit is provided here for the treatment of a human individual with lung cancer, comprising: (a) a dose of an anti-LAG-3 antibody; (b) a dose of an anti-PD-1 antibody; and (c) instructions for using the anti-LAG-3 antibody and the anti-PD-1 antibody in a method for treating a human individual with lung cancer.

[00567] Anti-LAG-3 antibody and anti-PD-1 antibodies may be provided in any of the doses or dose combinations described herein.

[00568] In some respects, the kit comprises a dose of relatlimab and a dose of an anti-PD-1 antibody as described herein. In some respects, the anti-PD-1 antibody is nivolumab, pembrolizumab, cemiplimab, or espartalizumab. In some respects, the anti-PD-1 antibody is nivolumab.

[00569] In some respects, the kit comprises one dose of favezelimab and one dose of an anti-PD-1 antibody as described herein. In some respects, the anti-PD-1 antibody is nivolumab, pembrolizumab, cemiplimab, or espartalizumab. In some respects, the anti-PD-1 antibody is pembrolizumab.

[00570] In some respects, the kit comprises fianlimab and an anti-PD-1 antibody as described herein. In some respects, the anti-PD-1 antibody is nivolumab, pembrolizumab, cemiplimab, or espartalizumab. In some respects, the anti-PD-1 antibody is cemiplimab.

[00571] In some respects, the kit comprises ieramilimab and a Petition 870260055013, dated 08 / 06 / 2026, page 159 / 490 154 / 189 anti-PD-1 antibody as described herein. In some respects, the anti-PD-1 antibody is nivolumab, pembrolizumab, cemiplimab, or espartalizumab. In some respects, the anti-PD-1 antibody is espartalizumab.

[00572] In some respects, the kit comprises an anti-LAG-3 antibody to anti-PD-1 antibody ratio of approximately 1:1, approximately 1:2, approximately 1:3, approximately 1:4, approximately 1:5, approximately 1:6, approximately 1:7, approximately 1:8, approximately 1:9, approximately 1:10, approximately 1:15, approximately 1:20, approximately 1:30, approximately 1:40, approximately 1:50, approximately 1:60, approximately 1:70, approximately 1:80, approximately 1:90, approximately 1:100, approximately 1:120, approximately 1:140, approximately 1:160, approximately 1:180, approximately 1:200, approximately 200:1, approximately 180:1, approximately 160:1, approximately 140:1, approximately 120:1, approximately 100:1, approximately 90:1, approximately 80:1, approximately 70:1, approximately 60:1, approximately 50:1, approximately 40:1, approximately 30:1, approximately 20:1, approximately 15:1, approximately 10:1, approximately 9:1, approximately 8:1, approximately 7:1, approximately 6:1, approximately 5:1, approximately 4:1, approximately 3:1 or approximately 2:1.

[00573] In some respects, the kit comprises an anti-LAG-3 antibody to anti-PD-1 antibody ratio of approximately 1:3.

[00574] In some respects, the kit comprises an anti-LAG-3 antibody to anti-PD-1 antibody ratio of approximately 1:1

[00575] In some respects, the kit comprises an anti-LAG-3 antibody to anti-PD-1 antibody ratio of approximately 2:1.

[00576] In some respects, the kit comprises an anti-LAG-3 antibody to anti-PD-1 antibody ratio of approximately 4:1.

[00577] In some respects, the total amount of anti-LAG-3 and anti-PD-1 antibodies in the kit is approximately 20 mg / mL, approximately 25 mg / mL, approximately 30 mg / mL, approximately 35 mg / mL, approximately 40 mg / mL, approximately 45 mg / mL, approximately 50 mg / mL, approximately 55 mg / mL, approximately 60 mg / mL, approximately 65 mg / mL, approximately 70 mg / mL, approximately 75 mg / mL, Petition 870260055013, dated 08 / 06 / 2026, page 160 / 490 155 / 189 about 80 mg / mL, about 85 mg / mL, about 90 mg / mL, about 95 mg / mL, about 100 mg / mL, about 105 mg / mL, about 110 mg / mL, approximately 115 mg / mL, approximately 120 mg / mL, approximately 125 mg / mL, approximately 130 mg / mL, approximately 135 mg / mL, approximately 140 mg / mL, approximately 145 mg / mL, approximately 150 mg / mL, approximately 155 mg / mL, approximately 160 mg / mL, approximately 165 mg / mL, approximately 170 mg / mL, approximately 175 mg / mL, approximately 180 mg / mL, approximately 185 mg / mL, approximately 190 mg / mL, approximately 195 mg / mL, approximately 200 mg / mL, approximately 205 mg / mL, approximately 210 mg / mL, approximately 215 mg / mL, approximately 220 mg / mL approximately 225 mg / mL, approximately 230 mg / mL, approximately 235 mg / mL, approximately 240 mg / mL, approximately 245 mg / mL, approximately 250 mg / mL, approximately 255 mg / mL, approximately 260 mg / mL, approximately 265 mg / mL, approximately 270 mg / mL, approximately 275 mg / mL, approximately 280 mg / mL, approximately 285 mg / mL, approximately 290 mg / mL, approximately 295 mg / mL, approximately 300 mg / mL, approximately 305 mg / mL, approximately 310 mg / mL, approximately 315 mg / mL, approximately 320 mg / mL, approximately 325 mg / mL, approximately 330 mg / mL, approximately 335 mg / mL, approximately 340 mg / mL, approximately 345 mg / mL, approximately 350 mg / mL, approximately 355 mg / mL,about 360 mg / mL, about 365 mg / mL, about 370 mg / mL, about 375 mg / mL, about 380 mg / mL, about 385 mg / mL, about 390 mg / mL, about 395, mg / mL, about 400 mg / mL, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, about 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg, about 190 mg, about 200 mg, about 210 mg, about 220 mg, about 230 mg, about 240 mg, about 250 mg, about 260 mg, about 270 mg, about 280 mg, about 290 mg, about 300 mg, about 310 mg, about 320 mg, about 330 mg, about 340 mg, about 350 mg, about 360 mg, about 370 mg, about Petition 870260055013, dated 08 / 06 / 2026, page 161 / 490 156 / 189 approximately 380 mg, approximately 390 mg, approximately 400 mg, approximately 410 mg, approximately 420 mg, approximately 430 mg, approximately 440 mg, approximately 450 mg, approximately 460 mg, approximately 470 mg, approximately 480 mg, approximately 490 mg, approximately 500 mg, approximately 510 mg, approximately 520 mg, approximately 530 mg, approximately 540 mg, approximately 550 mg, approximately 560 mg, approximately 570 mg, approximately 580 mg, approximately 590 mg, approximately 600 mg, approximately 610 mg, approximately 620 mg, approximately 630 mg, approximately 640 mg, approximately 650 mg, approximately 660 mg, approximately 670 mg, approximately 680 mg, approximately 690 mg, approximately 700 mg, approximately 710 mg, approximately 720 mg, approximately 730 mg, approximately 740 mg, approximately 750 mg, approximately 760 mg, approximately 770 mg, approximately 780 mg, approximately 790 mg, approximately 800 mg, approximately 810 mg, approximately 820 mg, approximately 830 mg, approximately 840 mg, approximately 850 mg, approximately 860 mg, approximately 870 mg, approximately 880 mg, approximately 890 mg, approximately 900 mg, approximately 910 mg, approximately 920 mg, approximately 930 mg, approximately 940 mg, approximately 950 mgapproximately 960 mg, approximately 970 mg, approximately 980 mg, approximately 990 mg, approximately 1000 mg, approximately 1010 mg, approximately 1020 mg, approximately 1030 mg, approximately 1040 mg, approximately 1050 mg, approximately 1060 mg, approximately 1070 mg, approximately 1080 mg, approximately 1090 mg, approximately 1100 mg, approximately 1110 mg, approximately 1120 mg, approximately 1130 mg, approximately 1140 mg, approximately 1150 mg, approximately 1160 mg, approximately 1170 mg, approximately 1180 mg, approximately 1190 mg, approximately 1200 mg, approximately 1210 mg, approximately 1220 mg, approximately 1230 mg, approximately 1240 mg, approximately 1250 mg, approximately 1260 mg, approximately 1270 mg, approximately 1280 mg, approximately 1290 mg, approximately 1300 mg, approximately 1310 mg, approximately 1320 mg, approximately 1330 mg, approximately 1340 mg, approximately 1350 mg, approximately 1360 mg, approximately 1370 mg, approximately 1380 mg, approximately 1390 mg, approximately 1400 mg, approximately 1410 mg, about 1420 mg, about 1430 mg, about 1440 mg, about 1450 mg, about 1460 mg, about 1470 mg, about Petition 870260055013, dated 08 / 06 / 2026, page 162 / 490 157 / 189 1480 mg, about 1490 mg, about 1500 mg, about 1510 mg, about 1520 mg, about 1530 mg, about 1540 mg, about 1550 mg, about 1560 mg, about 1570 mg, about 1580 mg, about 1590 mg, about 1600 mg, about 1610 mg, about 1620 mg, about 1630 mg, about 1640 mg, about 1650 mg, about 1660 mg, about 1670 mg, about 1680 mg, about 1690 mg, about 1700 mg, about 1710 mg, about 1720 mg, about 1730 mg, about 1740 mg, about 1750 mg, about 1760 mg, approximately 1770 mg, or approximately 1780 mg.

[00578] In some respects, the total amount of anti-LAG-3 and anti-PD-1 antibodies in the kit is approximately 25 mg / mL.

[00579] In some respects, the total amount of anti-LAG-3 and anti-PD-1 antibodies in the kit is approximately 50 mg / mL.

[00580] In some respects, the total amount of anti-LAG-3 and anti-PD-1 antibodies in the kit is approximately 150 mg / mL.

[00581] In some respects, the total amount of anti-LAG-3 and anti-PD-1 antibodies in the kit is approximately 50 mg.

[00582] In some respects, the total amount of anti-LAG-3 and anti-PD-1 antibodies in the kit is approximately 320 mg.

[00583] In some respects, the total amount of anti-LAG-3 and anti-PD-1 antibodies in the kit is approximately 640 mg.

[00584] In some respects, the total amount of anti-LAG-3 and anti-PD-1 antibodies in the kit is approximately 720 mg.

[00585] In some respects, the total amount of anti-LAG-3 and anti-PD-1 antibodies in the kit is approximately 960 mg.

[00586] In some respects, the total amount of anti-LAG-3 and anti-PD-1 antibodies in the kit is approximately 1,000 mg.

[00587] In some respects, the total amount of anti-LAG-3 and anti-PD-1 antibodies in the kit is approximately 1,080 mg.

[00588] In some respects, the total amount of anti-Petition antibodies 870260055013, dated 08 / 06 / 2026, page 163 / 490 158 / 189 The LAG-3 and anti-PD-1 levels in the kit are approximately 1440 mg.

[00589] In some respects, the kit comprises approximately 10 mg / mL, approximately 12.5 mg / mL, approximately 15 mg / mL, approximately 17.5 mg / mL, approximately 20 mg / mL, approximately 22.5 mg / mL, approximately 25 mg / mL, approximately 27.5 mg / mL, approximately 30 mg / mL, approximately 32.5 mg / mL, approximately 35 mg / mL, approximately 37.5 mg / mL, approximately 40 mg / mL, approximately 42.5 mg / mL, approximately 45 mg / mL, approximately 47.5 mg / mL, approximately 50 mg / mL, approximately 55 mg / mL, approximately 60 mg / mL, approximately 65 mg / mL, approximately 70 mg / mL, approximately 75 mg / mL, about 80 mg / mL, about 85 mg / mL, about 90 mg / mL, about 95 mg / mL, about 100 mg / mL, about 105 mg / mL, about 110 mg / mL, about 115 mg / mL, about 120 mg / mL, about 125 mg / mL, 130 mg / mL, about 135 mg / mL, about 140 mg / mL, about 145 mg / mL, about 150 mg / mL, about 155 mg / mL, about 160 mg / mL, about 165 mg / mL, about 170 mg / mL, about 175 mg / mL, about 180 mg / mL, about 185 mg / mL, about 190 mg / mL, about 195 mg / mL, about 200 mg / mL, about 7 mg, about 21 mg,about 40 mg, about 70 mg, about 80 mg, about 160 mg, about 200 mg, about 210 mg, about 300 mg, about 400 mg, about 480 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 960 mg, about 1000 mg, about 1100 mg, about 1200 mg or about 1300 mg of an anti-LAG-3 antibody. In some respects, the kit comprises approximately 5 mg / mL, approximately 10 mg / mL, approximately 12.5 mg / mL, approximately 15 mg / mL, approximately 17.5 mg / mL, approximately 20 mg / mL, approximately 22.5 mg / mL, approximately 25 mg / mL, approximately 27.5 mg / mL, approximately 30 mg / mL, approximately 32.5 mg / mL, approximately 35 mg / mL, approximately 37.5 mg / mL, approximately 40 mg / mL, approximately 42.5 mg / mL, approximately 45 mg / mL, approximately 47.5 mg / mL, approximately 50 mg / mL, approximately 55 mg / mL, approximately 60 mg / mL, approximately 65 mg / mL, approximately 70 mg / mL, approximately 75 mg / mL, about 80 mg / mL, about, Petition 870260055013, dated 08 / 06 / 2026, page 164 / 490 159 / 189 mg / mL, about 90 mg / mL, about 95 mg / mL, about 100 mg / mL, about 105 mg / mL, about 110 mg / mL, about 115 mg / mL, about 120 mg / mL, about 125 mg / mL, 130 mg / mL, about 135 mg / mL, about 140 mg / mL, about 145 mg / mL, about 150 mg / mL, about 155 mg / mL, about 160 mg / mL, about 165 mg / mL, about 170 mg / mL, about 175 mg / mL, about 180 mg / mL, about 185 mg / mL, about 190 mg / mL, about 195 mg / mL, about 200 mg / mL, about 10 mg, about 40 mg, about 100 mg, about 200 mg, about 240 mg, about 300 mg, about 350 mg, about 360 mg, about 400 mg or about 480 mg of an anti-PD-1 antibody.

[00590] In some respects, the kit comprises approximately 12.5 mg / mL of an anti-LAG-3 antibody and approximately 37.5 mg / mL of an anti-PD-1 antibody.

[00591] In some respects, the kit comprises approximately 20 mg / mL of an anti-LAG-3 antibody and approximately 5 mg / mL of an anti-PD-1 antibody.

[00592] In some respects, the kit comprises approximately 75 mg / mL of an anti-LAG-3 antibody and approximately 75 mg / mL of an anti-PD-1 antibody.

[00593] In some respects, the kit comprises approximately 100 mg / mL of an anti-LAG-3 antibody and approximately 50 mg / mL of an anti-PD-1 antibody.

[00594] In some respects, the kit comprises approximately 80 mg of an anti-LAG-3 antibody and approximately 240 mg of an anti-PD1 antibody.

[00595] In some respects, the kit comprises approximately 160 mg of an anti-LAG-3 antibody and approximately 480 mg of an anti-PD1 antibody.

[00596] In some respects, the kit comprises approximately 360 mg of Petition 870260055013, dated 08 / 06 / 2026, page 165 / 490 160 / 189 of an anti-LAG-3 antibody and approximately 360 mg of an anti-PD1 antibody.

[00597] In some respects, the kit comprises approximately 480 mg of an anti-LAG-3 antibody and approximately 480 mg of an anti-PD1 antibody.

[00598] In some respects, the kit comprises approximately 720 mg of an anti-LAG-3 antibody and approximately 360 mg of an anti-PD1 antibody.

[00599] In some respects, the kit comprises approximately 800 mg of an anti-LAG-3 antibody and approximately 200 mg of an anti-PD1 antibody.

[00600] In some respects, the kit comprises approximately 960 mg of an anti-LAG-3 antibody and approximately 480 mg of an anti-PD1 antibody.

[00601] A kit is provided here for treating a human individual with lung cancer, comprising: (a) 360 mg of an anti-LAG-3 antibody; (b) 360 mg of an anti-PD-1 antibody; and (c) instructions for using the anti-LAG-3 antibody and the anti-PD-1 antibody in a method for treating a human individual with lung cancer.

[00602] A kit is provided here for treating a human individual with lung cancer, comprising: (a) 720 mg of an anti-LAG-3 antibody; (b) 360 mg of an anti-PD-1 antibody; and (c) instructions for using the anti-LAG-3 antibody and the anti-PD-1 antibody in a method for treating a human individual with lung cancer.

[00603] A kit is provided here for the treatment of a human individual with lung cancer, comprising: (a) an anti-LAG-3 antibody; (b) an anti-PD-1 antibody; and (c) instructions for preparing each of the antibodies in a quantity of 360 mg and using the antibodies in a method for treating a human individual with lung cancer. Petition 870260055013, dated 08 / 06 / 2026, page 166 / 490 161 / 189

[00604] A kit is provided here for the treatment of a human individual with lung cancer, comprising: (a) an anti-LAG-3 antibody; (b) an anti-PD-1 antibody; and (c) instructions for preparing the anti-LAG-3 and anti-PD-1 antibodies in amounts of 720 mg and 360 mg, respectively, and using the antibodies in a method for treating a human individual with lung cancer.

[00605] In some respects, anti-LAG-3 and anti-PD-1 antibodies are co-packaged in a single unit dosage form.

[00606] In some respects, anti-LAG-3 and anti-PD-1 antibodies are packaged as separate unit dosage forms.

[00607] In some respects, 40 mg of anti-LAG-3 antibody is supplied in a single-dose form.

[00608] In some respects, 80 mg of anti-LAG-3 antibody is supplied in a single-dose form.

[00609] In some respects, 160 mg of anti-LAG-3 antibody is supplied in a single-dose form.

[00610] In some respects, 360 mg of anti-LAG-3 antibody are supplied in a single-dose form.

[00611] In some respects, 480 mg of anti-LAG-3 antibody are supplied in a single-dose form.

[00612] In some respects, 720 mg of anti-LAG-3 antibody are supplied in a single-dose form.

[00613] In some respects, 800 mg of anti-LAG-3 antibody are supplied in a single-dose form.

[00614] In some respects, 960 mg of anti-LAG-3 antibody are supplied in a single-dose form.

[00615] In some respects, 12.5 mg / mL of anti-LAG-3 antibody is supplied in a unit dosage form.

[00616] In some respects, 20 mg / mL of anti-LAG-3 antibody is provided in a unit dosage form. Petition 870260055013, dated 08 / 06 / 2026, page 167 / 490 162 / 189

[00617] In some respects, 50 mg / mL of anti-LAG-3 antibody is supplied in a unit dosage form.

[00618] In some respects, 75 mg / mL of anti-LAG-3 antibody is supplied in a unit dosage form.

[00619] In some respects, 100 mg / mL of anti-LAG-3 antibody is supplied in a unit dosage form.

[00620] In some respects, 130 mg / mL of anti-LAG-3 antibody is provided in a unit dosage form.

[00621] In some respects, 150 mg / mL of anti-LAG-3 antibody is provided in a unit dosage form.

[00622] In some respects, 175 mg / mL of anti-LAG-3 antibody is provided in a unit dosage form.

[00623] In some respects, 200 mg / mL of anti-LAG-3 antibody is supplied in a unit dosage form.

[00624] In some respects, 10 mg of anti-PD-1 antibody is supplied in a single-dose form.

[00625] In some respects, 40 mg of anti-PD-1 antibody is supplied in a single-dose form.

[00626] In some respects, 100 mg of anti-PD-1 antibody is supplied in a single-dose form.

[00627] In some respects, 200 mg of anti-PD-1 antibody are supplied in a single-dose form.

[00628] In some respects, 240 mg of anti-PD-1 antibody are supplied in a single-dose form.

[00629] In some respects, 360 mg of anti-PD-1 antibody are supplied in a single-dose form.

[00630] In some respects, 480 mg of anti-PD-1 antibody are supplied in a single-dose form.

[00631] In some respects, 5 mg / mL of anti-PD-1 antibody is supplied in a unit dosage form. Petition 870260055013, dated 08 / 06 / 2026, page 168 / 490 163 / 189

[00632] In some respects, 10 mg / mL of anti-PD-1 antibody is supplied in a unit dosage form.

[00633] In some respects, 37.5 mg / mL of anti-PD-1 antibody is provided in a unit dosage form.

[00634] In some respects, 50 mg / mL of anti-PD-1 antibody is supplied in a unit dosage form.

[00635] In some respects, 75 mg / mL of anti-PD-1 antibody is supplied in a unit dosage form.

[00636] In some respects, 100 mg / mL of anti-PD-1 antibody is supplied in a unit dosage form.

[00637] In some respects, 175 mg / mL of anti-PD-1 antibody is provided in a unit dosage form.

[00638] In some respects, 200 mg / mL of anti-PD-1 antibody is supplied in a unit dosage form.

[00639] In some aspects, the unit dosage form comprises from about 5 mM to about 50 mM of histidine, from about 50 mM to about 300 mM of sucrose, from about 5 μM to about 1 mM of diethylenetriaminepentaacetic acid (DTPA) or ethylenediaminetetraacetic acid (EDTA), and from about 0.001% to about 1% (w / v) of polysorbate or poloxamer (for example, polysorbate 80 (PS80), polysorbate 20 (PS20), poloxamer 188 (PX188) or any combination thereof).

[00640] In some respects, the unit dosage form comprises approximately 20 mM histidine, approximately 250 mM sucrose, approximately 50 μM DTPA and 0.05% PS80.

[00641] In some aspects, the unit dosage form comprises a pH of about 5 to about 6.5. In some aspects, the pH is about 5.3 to about 6.3. In some aspects, the pH is 5.8. In some aspects, the pH is 5.7.

[00642] In some respects, the unit dosage form is a Petition 870260055013, dated 08 / 06 / 2026, p. 169 / 490 164 / 189 vial, syringe, or intravenous bag. In some respects, the unit dose form is an autoinjector. In some respects, the unit dose form is a vial comprising a stopper and a seal. In some respects, the total volume in the vial is approximately 5 mL, approximately 6 mL, approximately 7 mL, approximately 8 mL, approximately 9 mL, approximately 10 mL, approximately 11 mL, approximately 12 mL, approximately 13 mL, approximately 14 mL, approximately 15 mL, approximately 16 mL, approximately 17 mL, approximately 18 mL, approximately 19 mL, or approximately 20 mL.

[00643] In some respects, the kit provides instructions for administering the anti-LAG-3 antibody and / or the anti-PD-1 antibody intravenously over approximately 30 minutes.

[00644] In some respects, the kit also includes therapeutic agents for one or more PDCTs as disclosed in this document. In some respects, the therapeutic agents for one or more PDCTs are carboplatin and paclitaxel, carboplatin and albumin-bound paclitaxel, carboplatin and pemetrexed, and / or cisplatin and pemetrexed. In some respects, the therapeutic agents are carboplatin, cisplatin, paclitaxel, albumin-bound paclitaxel, and pemetrexed.

[00645] All references cited above, as well as all references cited herein, are incorporated herein by reference in their entirety.

[00646] The following examples are offered for illustrative purposes only and not as a limitation. EXAMPLES EXAMPLE 1 Combination of Anti-LAG-3 and Anti-PD-1 Antibodies with Chemotherapy for Lung Cancer Treatment

[00647] A multicenter randomized study (Study A) will evaluate the efficacy and safety of the combination of nivolumab plus relatlimab with chemotherapy versus the combination of nivolumab with chemotherapy. Petition 870260055013, dated 08 / 06 / 2026, page 170 / 490 165 / 189 pia in adults with untreated stage IV or recurrent non-small cell lung cancer (NSCLC). The study will be conducted in two parts: Part 1, a blinded confirmation of dose safety at the site and in the individual; and Part 2, a double-blind, randomized, controlled study.

[00648] Another multicenter randomized study (Study B) will evaluate the efficacy and safety of the combination of nivolumab plus relatlimab with chemotherapy versus the combination of pembrolizumab with chemotherapy in adults with untreated Stage IV or recurrent NSCLC. Patient inclusion / exclusion criteria

[00649] Patients will be adult males and females > 18 years of age or local age of majority selected based on the following eligibility criteria: (1) histologically confirmed metastatic NSCLC of squamous (SQ) or non-squamous (NSQ) histology with Stage IV A / B (as defined by the 8th International Association for the Study of Lung Cancer Classification) or recurrent disease after multimodal therapy for locally advanced disease; (2) measurable disease by computed tomography or magnetic resonance imaging according to RECIST v1 criteria.1 with radiographic evaluation of the tumor performed up to 28 days before randomization; (3) no prior systemic anticancer treatment administered as primary therapy for advanced or metastatic disease; (4) ECOG PS of < 1 at screening and confirmed before randomization; (5) life expectancy of at least 3 months at the time of the first dose; (6) a formalin-fixed, paraffin-embedded tissue block containing sufficient tissue to cut 20 sections or a minimum of 20 unstained slides of tumor tissue from central biopsy, punch biopsy, excisional biopsy, or surgical specimen obtained during screening or before enrollment (within 3 months of enrollment, if applicable). Petition 870260055013, dated 08 / 06 / 2026, page 171 / 490 166 / 189 stored at 2-8°C or within 2 months of registration if stored at room temperature and without intervening systemic anticancer treatment between the time of acquisition and registration); and (6) immunohistochemistry (IHC) results of PD-L1 and LAG-3 during the screening period prior to randomization (LAG-3 expression in immune cells and PD-L1 expression in tumor cells will be measured using analytically validated assays).

[00650] Prior definitive chemoradiation for locally advanced disease is permitted, provided the last administration of chemotherapy or radiotherapy (whichever was administered last) occurred at least 6 months prior to enrollment. Prior adjuvant or neoadjuvant chemotherapy for early-stage lung cancer is permitted if completed at least 6 months prior to the start of study treatment. Prior palliative radiotherapy for non-central nervous system (CNS) lesions must have been completed at least 2 weeks prior to treatment. Participants with symptomatic tumor lesions at baseline who may require palliative radiotherapy within 4 weeks of initial treatment are strongly encouraged to receive palliative radiotherapy prior to treatment.

[00651] The main exclusion criteria will be: (1) pregnant or breastfeeding women; (2) participants with EGFR, ALK, or ROS-1 mutations that are sensitive to available targeted inhibitory therapy (all participants with NSQ histology must have been tested for EGFR, ALK, or ROS-1 mutation status; participants with NSQ histology and unknown EGFR, ALK, or ROS-1 status are excluded); (3) participants with known BRAF V600E mutations that are sensitive to available targeted inhibitory therapy (participants with unknown or undetermined BRAF mutation status are eligible); (4) participants with untreated central nervous system metastases; (5) participants with leptomeningeal metastases Petition 870260055013, dated 08 / 06 / 2026, page 172 / 490 167 / 189 (carcinom...

Claims

1. Use of a lymphocyte activating gene 3 (LAG-3) antagonist, characterized as being intended for the manufacture of a drug for the treatment of lung cancer in a human individual.

2. Use according to claim 1, characterized in that the medicament is for treating lung cancer in a human individual, in combination with: (a) a platinum doublet chemotherapy (PDCT), (b) a programmed death-1 (PD-1) pathway inhibitor, or (c) a PDCT and a PD-1 pathway inhibitor.

3. Use, according to claim 1 or 2, characterized in that the LAG-3 antagonist comprises an anti-LAG-3 antibody and / or a soluble LAG-3 polypeptide.

4. Use according to claim 3, characterized in that the anti-LAG-3 antibody is: (a) a full-length antibody, (b) a monoclonal, human, humanized, chimeric or multispecific antibody, or (c) an F(ab')2 fragment, a Fab' fragment, a Fab fragment, an Fv fragment, an scFv fragment, a dsFv fragment, a dAb fragment or a single-chain binding polypeptide.

5. Use according to claim 3 or 4, characterized in that the anti-LAG-3 antibody comprises: (a) BMS-986016 (relatlimab), IMP731 (H5L7BW), MK4280 (28G-10, favezelimab), REGN3767 (fianlimab), GSK2831781, humanized BAP050, IMP-701 (LAG525, ieramilimab), aLAG3(0414), aLAG3(0416), Sym022, TSR-033, TSR-075, XmAb841 (XmAb22841), MGD013 (tebotelimab), BI754111, FS118, P 13B02-30, AVA -017, 25F7, AGEN1746, RO7247669, INCAGN02385, IBI-110, EMB-02, IBI323, LBL-007, ABL501, or an antigen-binding portion of Petition 870260055013, dated 08 / 06 / 2026, page.196 / 490 2 / 9 same, (b) the CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence presented in SEQ ID No:3 and CDR1, CDR2 and CDR3 domains of the variable light chain region with the sequence presented in SEQ ID No:4, (c) a CDR1, CDR2, and CDR3 of the variable heavy chain region comprising the sequences presented in SEQ ID No:5, 6, and 7, respectively, and; (a) variable light chain CDR1, CDR2, and CDR3 comprising the sequences presented in SEQ ID No. 8, 9, and 10, respectively, (d) variable heavy and light chain regions comprising the sequences presented in SEQ ID No. 3 and 4, respectively, (e) heavy and light chains comprising the sequences presented in SEQ ID No. 1 and 2, respectively, (f) heavy and light chains comprising the sequences presented in SEQ ID No. 21 and 2, respectively.

6. Use, according to claim 3, characterized in that the soluble LAG-3 polypeptide is IMP321 (ephtilagimod alfa).

7. Use, according to any one of claims 1 to 6, characterized in that it is further in combination with a tyrosine kinase inhibitor, an antiangiogenic agent, a checkpoint inhibitor, a checkpoint stimulator, a chemotherapeutic agent, an immunotherapeutic agent, a platinum agent, an alkylating agent, a taxane, a nucleoside analogue, an antimetabolite, a topoisomerase inhibitor, an anthracycline, a vinca alkaloid or any combination thereof.

8. Use, according to claim 7, characterized in that the checkpoint inhibitor comprises a protein inhibitor - Petition 870260055013, dated 08 / 06 / 2026, page. 197 / 490 3 / 9 in 4 (CTLA-4) associated with cytotoxic T lymphocytes, a T cell immunoglobulin and ITIM domain inhibitor (TIGIT) inhibitor, a T cell immunoglobulin and mucin-containing domain inhibitor-3 (TIM-3), a TIM-1 inhibitor, a TIM-4 inhibitor, a B7-H3 inhibitor, a B7-H4 inhibitor, a B and T cell attenuator (BTLA), a T cell activation domain V inhibitor (VISTA), an indoleamine 2,3-dioxygenase (IDO) inhibitor, a nicotinamide adenine dinucleotide phosphate oxidase isoform 2 (NOX2) inhibitor, an immunoglobulin-like receptor (KIR) killer cell inhibitor, an adenosine A2a receptor (A2aR) inhibitor, a transforming growth factor beta (TGF-β) inhibitor, a phosphoinositide 3-kinase inhibitor (PI3K), a CD47 inhibitor, a CD48 inhibitor,a CD73 inhibitor, a CD113 inhibitor, a sialic acid-binding immunoglobulin-like lectin-7 (SIGLEC-7) inhibitor, a SIGLEC-9 inhibitor, a SIGLEC-15 inhibitor, a glucocorticoid-induced TNFR-related protein (GITR) inhibitor, a galectin-1 inhibitor, a galectin-9 inhibitor, a carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM-1) inhibitor, a G protein-coupled receptor 56 (GPR56) inhibitor, a glycoprotein A repeat predominant inhibitor (GARP), a 2B4 inhibitor, a programmed death homolog-1 (PD1H) inhibitor, a leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) inhibitor, or any combination thereof.

9. Use, according to any one of claims 2 to 8, characterized in that the PD-1 pathway inhibitor comprises an anti-PD-1 antibody, an anti-PD-L1 antibody, a soluble PDL2 polypeptide and / or BMS-986189.

10. Use according to claim 9, characterized in that the anti-PD-1 antibody and / or the anti-PD-L1 antibody is: (a) a full-length antibody. Petition 870260055013, dated 08 / 06 / 2026, page 198 / 490 4 / 9 (b) a human, humanized, chimeric or multispecific monoclonal antibody, or (c) an F(ab')2 fragment, a Fab' fragment, a Fab fragment, an Fv fragment, an scFv fragment, a dsFv fragment, a dAb fragment, or a single-chain binding polypeptide.

11. Use according to claim 9 or 10, characterized in that the anti-PD-1 antibody comprises: (a) nivolumab, pembrolizumab, PDR001 (spartalizumab), MEDI-0680, TSR-042, cemiplimab, JS001, PF-06801591, BGBA317, BI 754091, INCSHR1210, GLS-010, AM-001, STI-1110, AGEN2034, MGA012, BCD-100, IBI308, SSI-361, or an antigen-binding portion thereof, (b) the CDR1, CDR2 and CDR3 domains of the variable heavy chain region with the sequence shown in SEQ ID No. 13 and the CDR1, CDR2 and CDR3 domains of the variable light chain region with the sequence presented in SEQ ID No:14, (c) a CDR1, CDR2, and CDR3 of variable heavy chain region comprising the sequences presented in SEQ ID No:15, 16, and 17, respectively, and;a CDR1, CDR2, and CDR3 variable light chain region comprising the sequences presented in SEQ ID No.: 18, 19, and 20, respectively, (d) variable heavy and light chain regions comprising the sequences presented in SEQ ID No.: 13 and 14, respectively, or (e) heavy and light chains comprising the sequences presented in SEQ ID No.: 11 and 12, respectively.; 12. Use, according to any one of claims 2 to 11, characterized in that it comprises: (a) a dose of about 360 mg or about 720 mg of the LAG-3 antagonist, and Petition 870260055013, dated 08 / 06 / 2026, page 199 / 490 5 / 9 (b) a dose of about 360 mg of a PD1 pathway inhibitor.

13. Use, according to any one of claims 2 to 12, characterized in that the LAG-3 antagonist and the PD-1 pathway inhibitor are formulated together.

14. Use according to claim 13, characterized in that the medicament comprising the LAG-3 antagonist and the PD-1 pathway inhibitor is to be administered from a single intravenous bag over approximately 30 minutes.

15. Use, according to any one of claims 2 to 12, characterized in that the LAG-3 antagonist and the PD-1 pathway inhibitor are formulated separately.

16. Use, according to any one of claims 1 to 15, characterized in that: (a) the treatment is a first-line therapy, (b) the treatment is a second-line therapy, (c) the treatment is a third-line therapy, or (d) the individual has progressed on a previous therapy.

17. Use, according to any one of claims 1 to 16, characterized in that: (a) the lung cancer is unresectable, advanced, recurrent and / or metastatic; and / or (b) the individual suffers from Stage IV lung cancer.

18. Use, according to any one of claims 1 to 17, characterized in that the lung cancer is either small cell lung cancer or non-small cell lung cancer (NSCLC), optionally wherein the NSCLC has a squamous or non-squamous histology.

19. Use, according to any of claims 2 to 18, characterized in that the PDCT comprises a platinum agent in combination with a nucleoside analogue, an antimetabolite, a taxane, a vinca alkaloid or a topoisomerase inhibitor.

20. Use, according to any one of claims 2 to 19, characterized in that: (a) the human subject has Stage IV or recurrent NSCLC with squamous histology, the PDCT comprises: (i) a dose of carboplatin to a target area under the concentration-time curve of about 6 mg / mL^min, and (ii) a dose of about 200 mg / m2 of paclitaxel, or about 100 mg / m2 of albumin-bound paclitaxel, and the method is a first-line therapy; or (b) the human subject has Stage IV or recurrent NSCLC with non-squamous histology, the PDCT comprises: (i) a dose of carboplatin to a target area under the concentration-time curve of about 5 mg / mL^min or about 6 mg / mL^min or about 75 mg / mL*min of cisplatin, and (ii) a dose of about 500 mg / m2 of paclitaxel mg / m2 of pemetrexed, and the method is a first-line therapy.

21. Use, according to any of claims 1 to 20, characterized in that: (a) the lung cancer is recurrent after multimodal therapy for locally advanced lung cancer, (b) the individual has not received prior systemic therapy for cancer, the individual has not received prior systemic therapy for lung cancer or the individual has not received prior systemic therapy for advanced cancer or metastatic lung cancer, and / or Petition 870260055013, dated 06 / 08 / 2026, p. 201 / 490 7 / 9 (c) the individual has never received prior immuno-oncology therapy, the individual has never received prior immuno-oncology therapy for lung cancer or the lung cancer has never received prior immuno-oncology therapy.

22. Use, according to any one of claims 1 to 21, characterized in that one or more immune cells in the individual's tumor tissue express LAG-3 and / or one or more tumor cells in the subject's tumor tissue express PD-L1.

23. Use according to claim 22, characterized in that: (a) at least about 1%, at least about 3%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or about 100% of immune cells express LAG-3, and / or (b) at least about 1%, at least about 3%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about of 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, about 1% to about 50%, at least about 60%, at least about 70%, at least about 80%,at least about 90% or about 100% of tumor cells express PD-L1, 24. Composition, characterized by comprising a LAG-3 antagonist and a PD-1 pathway inhibitor.

25. Pharmaceutical composition, according to claim 24, characterized in that it comprises (a) about 360 mg or about 720 mg of the LAG-3 antagonist, and (b) about 360 mg of the PD-1 pathway inhibitor.

26. Kit, characterized by comprising: (a) a PDCT and a composition comprising an LAG-3 antagonist, (b) a composition comprising an LAG-3 antagonist and a composition comprising a PD-1 pathway inhibitor, (c) a PDCT, a composition comprising an LAG-3 antagonist and a PD-1 pathway inhibitor, wherein the PD-1 pathway inhibitor is in the composition with the LAG-3 antagonist or in a separate composition, or (d) the composition of claim 24 or 25 and a PDCT.

27. Combination characterized by comprising a LAG-3 antagonist and: (a) PDCT, (b) a PD-1 pathway inhibitor, or (c) a PDCT and a PD-1 pathway inhibitor.

28. Use of a lymphocyte activating gene-3 (LAG-3) antagonist, characterized by being for the manufacture of a drug to treat a human subject afflicted with lung cancer in a subject in need, in combination with a platinum doublet chemotherapy (PDCT), or a programmed cell death pathway-1 (PD-1) inhibitor, or a PDCT and a PD-1 pathway inhibitor.

29. Use of a lymphocyte-activating gene-3 (LAG-3) antagonist and a platinum doublet chemotherapy (PDCT), or a programmed cell death pathway-1 (PD-1) inhibitor, or a PDCT and a PD-1 pathway inhibitor, characterized by being for the manufacture of a drug to treat a human subject afflicted with lung cancer in a subject in need.

30. Use of the composition as defined in claim 24 or the combination as defined in claim 27, characterized by being for the manufacture of a medicament for use in therapy.