A Study of Tobemstomig Plus Platinum-Based Chemotherapy vs Pembrolizumab Plus Platinum-Based Chemotherapy in Participants With Previously Untreated Non-Small Cell Lung Cancer

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

• Histologically or cytologically documented locally advanced, unresectable (StageIIIB/IIIC) or metastatic (Stage IV) NSCLC who are not eligible for curative surgeryand/or definitive chemoradiotherapy

• No prior systemic treatment for metastatic NSCLC

• Known tumor PD-L1 status

• Confirmed availability of representative tumor specimens

• Measurable disease

• Life expectancy of at least 12 weeks

• Adequate hematologic and end-organ function

• Negative for HIV, hepatitis B (HBV), and hepatitis C (HCV)

• Adequate cardiovascular function

Exclusion Criteria:

• NSCLC known to have a mutation in the EGFR gene or an ALK fusion oncogene

• Symptomatic, untreated, or actively progressing central nervous system (CNS)metastases

• Untreated or clinically unstable spinal cord confession

• History of leptomeningeal disease

• Uncontrolled tumor-related pain

• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrentdrainage procedures (once a month or more frequently)

• Uncontrolled or symptomatic hypercalcemia

• Active or history of autoimmune disease or immune deficiency, including, but notlimited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupuserythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipidantibody syndrome, granulomatosis with polyangiitis, Sjögren syndrome,Guillain-Barré syndrome, or multiple sclerosis, with exceptions defined by theprotocol

• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitisobliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence ofactive pneumonitis on the screening chest computed tomography (CT) scan

• Active tuberculosis (TB) or untreated latent TB

• Current treatment with anti-viral therapy for HBV or HCV

• Significant cardiovascular disease within 3 months prior to randomization

• Major surgical procedure, other than for diagnosis, within 4 weeks prior toinitiation of study treatment, or anticipation of need for a major surgicalprocedure during the study

• History of malignancy other than NSCLC within 5 years prior to randomization, withthe exception of malignancies with a negligible risk of metastasis or death e.g., 5-year OS] rate > 90%), such as adequately treated carcinoma in situ of the cervix,non-melanoma skin carcinoma, localized prostate cancer, ductal breast carcinoma insitu, or Stage I uterine cancer

• Severe infection within 4 weeks prior to initiation of study treatment, including,but not limited to, hospitalization for complications of infection, bacteremia, orsevere pneumonia, or any active infection that could affect patient safety

• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiationof study treatment

• Prior allogeneic stem cell or solid organ transplantation

• Any other disease, metabolic dysfunction, physical examination finding, or clinicallaboratory finding that contraindicates the use of an investigational drug, mayaffect the interpretation of the results, or may render the patient at high riskfrom treatment complications

• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation ofstudy treatment, or anticipation of need for such a vaccine during study treatmentor within 5 months after the final dose of study treatment

• Treatment with investigational therapy within 28 days prior to initiation of studytreatment

• Any anti-cancer therapy, including hormonal therapy, within 21 days prior toinitiation of study treatment

• Prior treatment with CD137 agonists or immune checkpoint blockade therapies,including, but not limited to, anti-cytotoxic T lymphocyte-associated protein 4,anti-T cell immunoreceptor with Ig and tyrosine-based inhibition motif domains,anti-PD-1 and anti-PD-L1 therapeutic antibodies, and anti-LAG3) agents

• Treatment with systemic immunostimulatory agents (including, but not limited to,interferon and interleukin-2) within 4 weeks or 5 drug-elimination half lives (whichever is longer) prior to initiation of study treatment

• Treatment with systemic immunosuppressive medication (including, but not limited to,corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, andanti-tumor necrosis factor [TNF] agents) within 2 weeks prior to initiation of studytreatment, or anticipation of need for systemic immunosuppressive medication duringstudy treatment

• History of severe allergic anaphylactic reactions to chimeric or humanizedantibodies, fusion proteins, or platinum-containing compounds

• Known hypersensitivity to Chinese hamster ovary cell products or to any component ofthe tobemstomig or pembrolizumab formulation

• Known allergy or hypersensitivity or other contraindication to any component of thechemotherapy regimen the patient may receive during the study

• Pregnancy or breastfeeding