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

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of squamous non-small cell lungcancer (NSCLC) [Stage IV: M1a, M1b, M1c, American Joint Committee on Cancer StagingManual, version 8]

• Measurable disease per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 asassessed by the local site investigator/radiology

• Has life expectancy ≥3 months

• Has Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1assessed within 7 days prior to allocation

• Archival tumor tissue sample or newly obtained core, incisional, or excisionalbiopsy of a tumor lesion not previously irradiated has been provided

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

• Participants who are hepatitis B surface antigen (HBsAg)-positive are eligible ifthey have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeksand have undetectable HBV viral load before allocation

• Participants with history of hepatitis C virus (HCV) infection are eligible if HCVviral load is undetectable at screening

• Participants who have adverse events (AEs) due to previous anticancer therapies musthave recovered to ≤ Grade 1 or baseline (participants with endocrine-related AEs whoare adequately treated with hormone replacement are eligible)

• Has adequate organ function

• For Maintenance only (prior to randomization): is without disease progression oftheir NSCLC, as determined by BICR using RECIST 1.1 after completion ofstudy-specified Induction with an evaluable scan at Week 12

• For Maintenance only (prior to randomization): has ECOG PS of 0 or 1 as assessed atthe Prerandomization Visit

• For Maintenance only (prior to randomization): all AEs (with the exception ofalopecia, Grade 2 fatigue, and Grade ≤2 endocrine-related AEs requiring treatment orhormone replacement) have recovered

• For Maintenance only (prior to randomization): has adequate organ function

Exclusion Criteria:

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

• 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

• Active inflammatory bowel disease requiring immunosuppressive medication or previoushistory of inflammatory bowel disease

• Has uncontrolled, significant cardiovascular disease or cerebrovascular diseaseincluding 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 andcerebrovascular diseases within 6 months before study intervention

• HIV-infected participants who have been newly diagnosed or with a history ofKaposi'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 anotherstimulatory or coinhibitory T-cell receptor (eg, cytotoxic Tlymphocyte-associatedprotein 4, OX-40, CD137) [Note: Prior treatment with chemotherapy and/or radiationas a part of neoadjuvant or adjuvant therapy or chemoradiation therapy fornonmetastatic NSCLC is allowed as long as therapy was completed at least 12 monthsbefore diagnosis of metastatic NSCLC.]

• Received prior treatment with a tumor-associated calcium signal transducer 2 (TROP2)-targeted antidrug conjugate (ADC)

• Received radiation therapy to the lung that is >30 Gray 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

• Active inflammatory bowel disease requiring immunosuppressive medication or previoushistory of inflammatory bowel disease

• Participants who have not adequately recovered from major surgery or have ongoingsurgical complications

• Received prior treatment with a topoisomerase I inhibitor-containing ADC

• Is currently receiving a strong inducer/inhibitor of CYP3A4 that cannot bediscontinued for the duration of the study (the required washout period beforestarting sac-TMT is 2 weeks)

• Has a known additional malignancy that is progressing or has required activetreatment within the past 3 years.

• Has known central nervous system (CNS) metastases/carcinomatous meningitis (participants with previously treated brain metastases may participate provided theyare clinically stable for t least 2 weeks and, have no evidence of new or enlargingbrain metastases and also are off steroids 3 days prior to dosing with studymedication. Subjects with known untreated, asymptomatic brain metastases [ie, noneurological symptoms, no requirements for corticosteroids, no or minimalsurrounding edema, and no lesion >1.5 cm] may participate but will require regularimaging of the brain as a site of disease)

• Severe hypersensitivity (≥Grade 3) to study intervention and/or any of itsexcipients 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] isallowed)

• History of (noninfectious)pneumonitis/interstitial lung disease that requiredsteroids or has current pneumonitis/interstitial lung disease

• Active infection requiring systemic therapy

• History of allogeneic tissue/solid organ transplant