KEYMAKER-U01 Substudy 2: Efficacy and Safety Study of Pembrolizumab (MK-3475) When Used With Investigational Agents in Treatment-naïve Participants With Anti-programmed Cell Death Receptor Ligand 1 (PD-L1) Positive Advanced Non-small Cell Lung Cancer (NSCLC) (MK-3475-01B/KEYMAKER-U01B)

Inclusion:

• Has a histologically- or cytologically-confirmed diagnosis of Stage IV squamous ornon-squamous NSCLC

• Has non-squamous NSCLC and is not eligible for an approved targeted therapy

• Is able to provide archival tumor tissue sample collected either within 5 years orwithin the interval from completion of last treatment but before entering thescreening period or newly obtained core or excisional biopsy of a tumor lesion notpreviously irradiated obtained within 90 days of treatment initiation

• Has not received prior systemic treatment for metastatic NSCLC

• Has programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥1%

• Is able to complete all screening procedures within the 35-day screening window.

• Male participants must agree to use contraception and refrain from donating spermduring the treatment period and for at least 120 days after the last dose of studytreatment

• Female participants must not be pregnant or breastfeeding, and at least one of thefollowing conditions apply:

1. Not a woman of childbearing potential (WOCBP) OR

2. A WOCBP who agrees to use contraception during the treatment period and for atleast 120 days after the last dose of study treatment

• Has adequate organ function within 10 days of initiation of study treatment

Exclusion Criteria:

• Has a diagnosis of small cell lung cancer

• 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 before the first dose of study treatment

• Has a known additional malignancy that is progressing or has required activetreatment within the past 2 years

• Has known active central nervous system (CNS) metastases and/or carcinomatousmeningitis

• Has an active autoimmune disease that has required systemic treatment in the past 2years

• Has a history of (noninfectious) pneumonitis that required steroids or has currentpneumonitis

• Has an active infection requiring systemic therapy

• Has clinically significant cardiac disease, including unstable angina, acutemyocardial infarction within 6 months from Day 1 of study treatment, or New YorkHeart Association Class III or IV congestive heart failure

• Has a known history of Human Immunodeficiency Virus (HIV) infection

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

• Has known psychiatric or substance abuse disorders that would interfere withcooperating with the requirements of the study

• Has had major surgery <3 weeks before the first dose of study treatment

• Has received prior radiation therapy to the lung that is >30 Gray (Gy) within 6months of the first dose of study treatment

• Has received any prior immunotherapy and was discontinued from that treatment due toa severe or worse immune-related adverse event (irAE)

• Has had chemotherapy or biological cancer therapy within 4 weeks before the firstdose of study treatment or has not recovered to Common Terminology Criteria forAdverse Events (CTCAE) Grade 1 or better from the AEs due to cancer therapeuticsadministered more than 4 weeks before the first dose of study treatment (includingparticipants who had previous immunomodulatory therapy with residual irAEs)

• Has received a live vaccine within 30 days before the first dose of study treatment.Any licensed COVID-19 vaccine (including for Emergency Use) in a particular countryis allowed as long as they are messenger ribonucleic acid (mRNA) vaccines,adenoviral vaccines, or inactivated vaccines. Investigational vaccines (ie, thosenot licensed or approved for Emergency Use) are not allowed

• Has received prior systemic cytotoxic chemotherapy or other targeted or biologicalantineoplastic therapy for metastatic disease.

• 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 prior therapy targeting other immuno-regulatoryreceptors or mechanisms

• Is currently participating in or has participated in a study of an investigationalagent or has used an investigational device within 4 weeks before the first dose ofstudy treatment

• Has had a severe hypersensitivity reaction to treatment with monoclonal antibodies (including pembrolizumab) and/or any of their excipients

• Is pregnant or breastfeeding or expecting to conceive or father children within theprojected duration of the study, starting with the screening visit through 120 daysafter the last dose of study treatment

• Has had an allogenic tissue/solid organ transplant