A Study of Investigational Agents in Participants With Previously Treated Stage IV Nonsquamous Non-small Cell Lung Cancer (NSCLC) (MK-3475-01H/KEYMAKER-U01)

Inclusion Criteria

• Inclusion Criteria: The main inclusion criteria include but are not limited to the following: - Histologically or cytologically confirmed diagnosis of Stage IV nonsquamous non-small cell lung cancer (NSCLC) - Documented disease progression per RECIST 1.1 after receiving an anti-programmed cell death 1 protein (PD-1)/programmed cell death ligand 1 (PD-L1) treatment and platinum-based chemotherapy - Confirmation per local test report that epidermal growth factor receptor negative (EGFR-), anaplastic lymphoma kinase negative (ALK-), or c ros oncogene 1 negative (ROS1-) directed therapy is not indicated as primary therapy - Measurable disease per RECIST 1.1 as assessed by investigator and verified by BICR - Life expectancy of at least 3 months - An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days before randomization - Is an individual of any sex/gender who is at least 18 years of age at the time of providing the informed consent - Has adequate organ function - If capable of producing sperm refrains from donating sperm plus either abstains from penile-vaginal intercourse or uses a penile/external condom, with contraceptive use consistent with local regulations - Participant/participants of childbearing potential (POCBP) is not pregnant and has a negative highly sensitive pregnancy test; and is not breastfeeding and uses a highly effective contraceptive method - Archival tumor tissue sample of a tumor lesion not previously irradiated has been provided - Has provided tissue prior to treatment randomization from a newly obtained formalin-fixed sample from a new biopsy - Human Immunodeficiency Virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART) - Participants who are hepatitis B surface antigen (HBsAg) positive have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization - Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening Exclusion Criteria: The main exclusion criteria include but are not limited to the following: - Diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements - Received radiation therapy to the lung - Has uncontrolled or significant cardiovascular disorder prior to randomization - Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses - Participants who have adverse events (AEs) (other than alopecia) due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline - Has known severe hypersensitivity (≥Grade 3) to study intervention and/or any of its excipients - Has evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection (including HIV infection) - Has clinically significant corneal disease - Has received prior radiotherapy within 2 weeks of start of study intervention, or radiation related toxicities, requiring corticosteroids - Has inadequate washout period prior to randomization - Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention - Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy - Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration - Has known additional malignancy that is progressing or has required active treatment within the past 3 years - Has known untreated central nervous system (CNS) metastases and/or carcinomatous meningitis - Has evidence of any leptomeningeal disease - Has history of (noninfectious) pneumonitis/ interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD, and/or suspected ILD/pneumonitis - Has active autoimmune disease that has required systemic treatment in the past 2 years - Has active infection requiring systemic therapy - HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease - Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease - Has known history of, or active, neurologic paraneoplastic syndrome - Has history of allogeneic tissue/solid organ transplant - Have not adequately recovered from major surgery or have ongoing surgical complications