Pembrolizumab (MK-3475) Versus Placebo Following Surgery and Radiation in Participants With Locally Advanced Cutaneous Squamous Cell Carcinoma (MK-3475-630/KEYNOTE-630)

Inclusion Criteria:

• Has histologically confirmed cutaneous squamous cell carcinoma (cSCC) as the primarysite of malignancy (metastatic skin involvement from another type of primary canceror from an unknown primary cancer is not permitted)

• Has histologically confirmed LA cSCC with ≥1 high-risk feature(s) as the primarysite of malignancy

• Has undergone complete macroscopic resection of all known cSCC disease with orwithout microscopic positive margins. For those participants with residualmicroscopic positive margin involvement, confirmation that additional re-excision isnot possible must be provided

• Has completed adjuvant radiotherapy (RT) for LA cSCC with last dose of RT ≥4 weeksand ≤16 weeks from randomization

• Has received an adequate post-op dose of RT (either hypofractionated orconventional)

• Is disease free as assessed by the investigator with complete radiographic stagingassessment ≤28 days from randomization

• Is not pregnant or breastfeeding

• Is not a person of childbearing potential (POCBP)

• Has a negative pregnancy test ≤72 hours before the first dose of study intervention.

• Has provided an archival or newly-obtained tumor tissue sample adequate forProgrammed Cell Death Ligand 1 (PD-L1) testing as determined by central laboratorytesting

• Has a life expectancy of >3 months

• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 ≤10days prior to the first dose of study intervention.

Exclusion Criteria:

• Has macroscopic residual cSCC after surgery and/or recurrence with active cSCCdisease before randomization

• Has any other histologic type of skin cancer other than invasive cSCC (eg, basalcell carcinoma) that has not been definitively treated with surgery or radiation;Bowen's disease; Merkel cell carcinoma; or melanoma

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

• Has received prior systemic anticancer therapy including investigational agents forcSCC ≤4 weeks prior to before start of study intervention.

• Has not recovered from all radiation-related toxicities and has not had radiationpneumonitis

• Has received a live vaccine ≤30 days prior to the first dose of study intervention

• Has received an investigational agent or has used an investigational device within 4weeks prior to the first dose of study treatment.

• Has known additional malignancy that is progressing or has required active treatmentwithin the past 2 years. Note: Participants with basal cell carcinoma of the skin,squamous cell carcinoma of the skin or carcinoma in situ, excluding carcinoma insitu of the bladder, that have undergone potentially curative therapy are notexcluded. Other exceptions may be considered with Sponsor consultation. Note:Participants with low risk early-stage prostate cancer defined as below are notexcluded: Stage T1c or T2a with a Gleason score ≤6 and a prostate-specific antigen (≤10 ng/ml) either treated with definitive intent or untreated in activesurveillance that has been stable for the past year prior to study allocation. Earlystage asymptomatic CLL without prior treatment and without any of the risk features (unmutated IGHV, lymphocytes >15,000μL, palpable lymph nodes) will be eligible forthe study

• Has an active autoimmune disease that has required systemic treatment in past 2years except replacement therapy (eg, thyroxine, insulin, or physiologiccorticosteroid).

• Has a history of (noninfectious) pneumonitis/interstitial lung disease that requiredsteroids or has current pneumonitis/interstitial lung disease

• Has an active infection requiring systemic therapy

• Has a known history of human immunodeficiency virus (HIV) infection

• Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg]reactive) or known active hepatitis C virus (HCV; defined as HCV RNA [qualitative]is detected) infection

• 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 intervention

• Has had an allogeneic tissue/solid organ transplant