This study is evaluating a new drug (called MK-2870) when given in combination with immunotherapy, compared to immunotherapy alone, in people with metastatic non-small cell lung cancerA Randomized, Open-label, Phase 3 Study of MK-2870 in Combination With Pembrolizumab Compared to Pembrolizumab Monotherapy in the First-line Treatment of Participants With Metastatic Non-small Cell Lung Cancer With PD-L1 TPS Greater Than or Equal to 50%

Exclusion

• Diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements.
• Has Grade ≥2 peripheral neuropathy.
• History of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing.
• Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea).
• Has uncontrolled, significant cardiovascular disease or cerebrovascular disease within the 6 months preceding study intervention.
• Received prior systemic anticancer therapy for their metastatic NSCLC.
• Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor Note: Prior treatment with an anti-PD-1, anti-PD- L1, or anti-PD-L2 agent in the neoadjuvant or adjuvant setting for nonmetastatic resectable NSCLC is allowed as long as therapy was completed at least 12 months before diagnosis of metastatic NSCLC.
• Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
• Received radiation therapy to the lung that is >30 Gy within 6 months of start of study intervention.
• Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids.
• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
• Known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Known intolerance to MK-2870 or pembrolizumab and/or any of their excipients; for pembrolizumab, severe hypersensitivity (≥Grade 3) is exclusionary.
• Known hypersensitivity to MK-2870 or other biologic therapy.
• Active autoimmune disease that has required systemic treatment in the past 2 years.
• History of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD.
• Active infection requiring systemic therapy
• Concurrent active Hepatitis B and Hepatitis C virus infection.
• Human immunodeficiency virus (HIV)-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
• History of allogeneic tissue/solid organ transplant.
• Requires treatment with a strong inhibitor or inducer of Cytochrome P450 3A4 (CYP3A4) at least 14 days before the first dose of study intervention and throughout the study.