Pembrolizumab With or Without Maintenance Sacituzumab Tirumotecan (Sac-TMT; MK-2870) in Metastatic Squamous Non-small Cell Lung Cancer (NSCLC) [MK-2870-023]

Eligibility Criteria

• * Histologically or cytologically confirmed diagnosis of squamous squamous non-small cell lung cancer (NSCLC) \[Stage IV: M1a, M1b, M1c, American Joint Committee on Cancer Staging Manual, version 8\]
• * Measurable disease per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 as assessed by the local site investigator/radiology
• * Has life expectancy ≥3 months
• * Has Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1 assessed within 7 days prior to allocation
• * Archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated has been provided
• * Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
• * Participants who are hepatitis B surface antigen (HBsAg)-positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load before allocation
• * Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
• * Participants who have adverse events (AEs) due to previous anticancer therapies must have recovered to ≤ Grade 1 or baseline (participants with endocrine-related AEs who are adequately treated with hormone replacement are eligible)
• * Has adequate organ function
• * For Maintenance only (prior to randomization): is without disease progression of their NSCLC, as determined by BICR using RECIST 1.1 after completion of study-specified Induction with an evaluable scan at Week 12
• * For Maintenance only (prior to randomization): has ECOG PS of 0 or 1 as assessed at the Prerandomization Visit
• * For Maintenance only (prior to randomization): all AEs (with the exception of alopecia, Grade 2 fatigue, and Grade ≤2 endocrine-related AEs requiring treatment or hormone replacement) have recovered
• * For Maintenance only (prior to randomization): has adequate organ function
• * Diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements
• * 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
• * Active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
• * Has uncontrolled, significant cardiovascular disease or cerebrovascular disease including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to \>480 ms, and other serious cardiovascular and cerebrovascular diseases within 6 months before study intervention
• * HIV-infected participants who have been newly diagnosed or with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• * Received prior systemic anticancer therapy for their metastatic NSCLC
• * Received prior therapy with an anti-programmed cell death-1 (PD-1), anti-PD-Ligand 1 (PD-L1), or anti-PD-Lignad 2 (PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, cytotoxic Tlymphocyte-associated protein 4, OX-40, CD137) \[Note: Prior treatment with chemotherapy and/or radiation as a part of neoadjuvant or adjuvant therapy or chemoradiation therapy for nonmetastatic NSCLC is allowed as long as therapy was completed at least 12 months before diagnosis of metastatic NSCLC.\]
• * Received prior treatment with a tumor-associated calcium signal transducer 2 (TROP2)-targeted antidrug conjugate (ADC)
• * Received prior systemic anticancer therapy including investigational agents within 4 weeks before allocation
• * Received radiation therapy to the lung that is \>30 Gray 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
• * Active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
• * Participants who have not adequately recovered from major surgery or have ongoing surgical complications
• * Received prior treatment with a topoisomerase I inhibitor-containing ADC
• * Is currently receiving a strong inducer/inhibitor of CYP3A4 that cannot be discontinued for the duration of the study (the required washout period before starting sac-TMT is 2 weeks)
• * Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
• * Has known central nervous system (CNS) metastases/carcinomatous meningitis (participants with previously treated brain metastases may participate provided they are clinically stable for t least 2 weeks and, have no evidence of new or enlarging brain metastases and also are off steroids 3 days prior to dosing with study medication. Subjects with known untreated, asymptomatic brain metastases \[ie, no neurological symptoms, no requirements for corticosteroids, no or minimal surrounding edema, and no lesion \>1.5 cm\] may participate but will require regular imaging of the brain as a site of disease)
• * Severe hypersensitivity (≥Grade 3) to study intervention and/or any of its excipients or to another biologic therapy
• * Active autoimmune disease that has required systemic treatment in the past 2 years (replacement therapy \[eg, thyroxine, insulin, or physiologic corticosteroid\] is allowed)
• * History of (noninfectious)pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• * Active infection requiring systemic therapy
• * History of allogeneic tissue/solid organ transplant