Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab Versus Pembrolizumab Alone in Metastatic Non-small Cell Lung Cancer (NSCLC) With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥ 50% (MK-2870-007)

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of squamous or nonsquamous NSCLC

• Confirmation that epidermal growth factor receptor- (EGFR-), anaplasticlymphoma kinase- (ALK-), or proto-oncogene tyrosine-protein kinase ROS (ROS1-)directed therapy is not indicated as primary therapy

• Provided tumor tissue that demonstrates programmed cell death ligand 1 (PD-L1)expression in ≥50% of tumor cells as assessed by an immunohistochemistry (IHC)central laboratory

• An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1assessed within 7 days before randomization.

• A life expectancy of at least 3 months.

• Human immunodeficiency virus (HIV)-infected participants must have wellcontrolled HIV on antiretroviral therapy (ART)

Exclusion Criteria:

• Diagnosis of small cell lung cancer or, for mixed tumors, presence of small cellelements.

• Has Grade ≥2 peripheral neuropathy.

• History of documented severe dry eye syndrome, severe Meibomian gland disease and/orblepharitis, or corneal disease that prevents/delays corneal healing.

• Has active inflammatory bowel disease requiring immunosuppressive medication orprevious clear history of inflammatory bowel disease (eg, Crohn's disease,ulcerative colitis, or chronic diarrhea).

• Has uncontrolled, significant cardiovascular disease or cerebrovascular diseasewithin 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 withan agent directed to another stimulatory or coinhibitory T-cell receptor Note: Priortreatment with an anti-PD-1, anti-PD- L1, or anti-PD-L2 agent in the neoadjuvant oradjuvant setting for nonmetastatic resectable NSCLC is allowed as long as therapywas completed at least 12 months before diagnosis of metastatic NSCLC.

• Received prior systemic anticancer therapy including investigational agents within 4weeks before randomization.

• Received radiation therapy to the lung that is >30 Gy within 6 months of start ofstudy intervention.

• Received prior radiotherapy within 2 weeks of start of study intervention, orradiation-related toxicities, requiring corticosteroids.

• Received a live or live-attenuated vaccine within 30 days before the first dose ofstudy 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 treatmentwithin the past 3 years.

• Known active central nervous system (CNS) metastases and/or carcinomatousmeningitis.

• Known intolerance to sacituzumab tirumotecan or pembrolizumab and/or any of theirexcipients; for pembrolizumab, severe hypersensitivity (≥Grade 3) is exclusionary.

• Known hypersensitivity to sacituzumab tirumotecan 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 requiredsteroids 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'ssarcoma 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 throughoutthe study.