Coformulation of Pembrolizumab/Vibostolimab (MK-7684A) Versus Pembrolizumab (MK-3475) Monotherapy for Programmed Cell Death 1 Ligand 1 (PD-L1) Positive Metastatic Non-Small Cell Lung Cancer (MK-7684A-003, KEYVIBE-003)

Inclusion Criteria:

• Has a histologically or cytologically confirmed diagnosis of Stage IV: M1a, M1b, orM1c non-small cell lung cancer (NSCLC) per the American Joint Committee on Cancer (AJCC) Staging Manual, version 8

• Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, as determined by the local site assessment

• Has confirmation that epidermal growth factor receptor (EGFR)-, anaplastic lymphomakinase (ALK)-, or reactive oxygen species proto-oncogene 1 (ROS1)-directed therapyis not indicated as primary therapy and absence of ALK and ROS1 gene rearrangements

• Has provided tumor tissue that demonstrates Programmed Cell Death 1 Ligand 1 (PD-L1)expression in ≥1% of tumor cells as assessed by immunohistochemistry (IHC) at acentral laboratory

• Has an Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1assessed within 7 days prior to randomization

• Has a life expectancy of at least 3 months

• A female participant is eligible to participate if she is not pregnant orbreastfeeding, and at least one of the following conditions applies:

• Is not a woman of childbearing potential (WOCBP)

• Is a WOCBP and using a contraceptive method that is highly effective (with afailure rate of <1% per year), with low user dependency or be abstinent fromheterosexual intercourse as their preferred and usual lifestyle (abstinent on along term and persistent basis), during the intervention period and for atleast 120 days after the last dose of study intervention

• Has adequate organ function

Exclusion Criteria:

• Has a known history of an additional malignancy, except if the participant hasundergone potentially curative therapy with no evidence of that disease recurrencefor at least 3 years since initiation of that therapy

• Has received prior systemic chemotherapy or other targeted or biologicalantineoplastic therapy for their metastatic NSCLC.

• Prior treatment with chemotherapy and/or radiation as part ofneoadjuvant/adjuvant or chemoradiation therapy for nonmetastatic NSCLC isallowed as long as therapy was completed at least 6 months before the diagnosisof metastatic NSCLC.

• Participants must have recovered from all AEs due to previous therapies toGrade ≤1 or baseline. Participants with Grade ≤2 neuropathy may be eligible.Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormonereplacement may be eligible.

• Has received prior therapy with an anti-programmed cell death receptor 1 (PD-1),anti-programmed cell death receptor ligand 1 (PD-L1), or anti-programmed cell deathreceptor ligand 2 (PD-L2) agent or with an agent directed to another stimulatory orco-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX-40, CD137)

• Has received previous treatment with another agent targeting the T cellimmunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitionmotif (ITIM) domains (TIGIT) receptor pathway

• Has received radiotherapy within 2 weeks of start of study intervention.Participants must have recovered from all radiation-related toxicities, not requirecorticosteroids, and not have had radiation pneumonitis. A 1-week washout ispermitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervoussystem (CNS) disease

• Has received a live or live-attenuated vaccine within 30 days prior to the firstdose of study intervention. Administration of killed vaccines is allowed.

• Any licensed COVID-19 vaccine (including for Emergency Use) in a particularcountry is allowed in the study as long as they are mRNA vaccines, adenoviralvaccines, or inactivated vaccines. These vaccines will be treated just as anyother concomitant therapy.

• Investigational vaccines (i.e., those not licensed or approved for EmergencyUse) are not allowed.

• Is currently participating in or has participated in a study of an investigationalagent or has used an investigational device within 4 weeks prior to the first doseof study intervention

• Has known active or untreated CNS metastases and/or carcinomatous meningitis.Participants with previously treated brain metastases may participate provided theyare radiologically stable for at least 4 weeks by repeat imaging, clinically stable,and without requirement of steroid treatment for at least 14 days prior to firstdose of study intervention

• Has severe hypersensitivity (≥Grade 3) to pembrolizumab/vibostolimab orpembrolizumab and/or any of its excipients

• Has an active autoimmune disease that has required systemic treatment in past 2years (ie, with use of disease modifying agents, corticosteroids, orimmunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, orphysiologic corticosteroid replacement therapy for adrenal or pituitaryinsufficiency) is not considered a form of systemic treatment and is allowed.

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form ofimmunosuppressive therapy within 7 days prior to the first dose of studyintervention

• Has a history of (non-infectious) pneumonitis that required steroids or has currentpneumonitis

• Has a known history of interstitial lung disease. Lymphangitic spread of the NSCLCis not exclusionary.

• Has an active infection requiring systemic therapy

• Has a known history of human immunodeficiency virus (HIV) infection. No HIV testingis required unless mandated by local health authority

• Has a known history of Hepatitis B or known active Hepatitis C virus infection

• Has a history or current evidence of any condition, therapy, or laboratoryabnormality that prevents the participant from receiving platinum-doubletchemotherapy for first line NSCLC, or that might confound the results of the study,interfere with the participant's participation for the full duration of the study,or is not in the best interest of the participant to participate, in the opinion ofthe treating investigator.

• Has a known psychiatric or substance abuse disorder that would interfere with theparticipant's ability to cooperate with the requirements of the study