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

Eligibility Criteria

• * Histologically or cytologically confirmed diagnosis of Stage IV nonsquamous non-small cell lung cancer (NSCLC)
• * Documented disease progression as assessed by investigator using RECIST 1.1 after receiving both anti-PD-(L)1 therapy and platinum-based chemotherapy per local standard of care. These can be given together or in sequence.
• * 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
• * 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 active 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 concurrent active Hepatitis B and Hepatitis C virus infection
• * 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
• * Participants who are incapacitated