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

COMPLETEDPHASE3

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

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate Pembrolizumab Versus Placebo as Adjuvant Therapy Following Surgery and Radiation in Participants With High-risk Locally Advanced Cutaneous Squamous Cell Carcinoma (LA cSCC) (KEYNOTE-630)

NCT03833167•Merck Sharp & Dohme LLC

View on ClinicalTrials.gov

Summary

This is a randomized, double-blind, study that compares pembrolizumab (MK-3475) with placebo given as adjuvant therapy in participants with high-risk locally advanced cutaneous squamous cell carcinoma (LA cSCC) that have undergone surgery with curative intent in combination with radiotherapy. The primary hypothesis is that pembrolizumab is superior to placebo in increasing recurrence free survival (RFS).

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Has histologically confirmed cutaneous squamous cell carcinoma (cSCC) as the primary site of malignancy (metastatic skin involvement from another type of primary cancer or from an unknown primary cancer is not permitted)
•Has histologically confirmed locally advanced cutaneous squamous cell carcinoma (LA cSCC) with ≥1 high-risk feature(s) as the primary site of malignancy
•Has undergone complete macroscopic resection of all known cSCC disease with or without microscopic positive margins. For those participants with residual microscopic positive margin involvement, confirmation that additional re-excision is not possible must be provided
•Has completed adjuvant radiotherapy (RT) for LA cSCC with last dose of RT ≥4 weeks and ≤16 weeks from randomization
•Has received an adequate post-op dose of RT (either hypofractionated or conventional)
•Is disease free as assessed by the investigator with complete radiographic staging assessment ≤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 for Programmed Cell Death Ligand 1 (PD-L1) testing as determined by central laboratory testing
+2 more criteria

Exclusion Criteria

•Has macroscopic residual cSCC after surgery and/or recurrence with active cSCC disease before randomization
•Has any other histologic type of skin cancer other than invasive cSCC (eg, basal cell 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 an agent 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 for cSCC ≤4 weeks prior to before start of study intervention.
•Has not recovered from all radiation-related toxicities and has not had radiation pneumonitis
•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 4 weeks prior to the first dose of study treatment.
•Has known additional malignancy that is progressing or has required active treatment within 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 in situ of the bladder, that have undergone potentially curative therapy are not excluded. Other exceptions may be considered with Sponsor consultation. Note: Participants with low risk early-stage prostate cancer defined as below are not excluded: 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 active surveillance that has been stable for the past year prior to study allocation. Early stage asymptomatic CLL without prior treatment and without any of the risk features (unmutated IGHV, lymphocytes \>15,000μL, palpable lymph nodes) will be eligible for the study
•Has an active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid).
•Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
+5 more criteria

Locations (181)

University of South Alabama, Mitchell Cancer Institute ( Site 1562)

Mobile, Alabama, United States

City of Hope Medical Center ( Site 1505)

Duarte, California, United States

UCSD Moores Cancer Center ( Site 1561)

La Jolla, California, United States

UCLA Hematology/Oncology - Westwood (Building 100) ( Site 1568)

Los Angeles, California, United States

University of California Davis Comprehensive Cancer Center ( Site 1560)

Sacramento, California, United States

Stanford University Medical Center ( Site 1503)

Stanford, California, United States

University of Colorado Cancer Center ( Site 1506)

Aurora, Colorado, United States

Smilow Cancer Center at Yale-New Haven ( Site 1507)

New Haven, Connecticut, United States

Boca Raton Regional Hospital ( Site 1551)

Boca Raton, Florida, United States

UF Health ( Site 1511)

Gainesville, Florida, United States

Key Dates

Start Date

April 1, 2019

Primary Completion Date

June 28, 2024

Completion Date

January 20, 2026

Last Updated

March 10, 2026

Enrollment

450

ACTUAL participants

Conditions

Carcinoma, Squamous Cell

Interventions

Pembrolizumab

BIOLOGICAL

Placebo

DRUG

Circulating Tumor DNA (ctDNA) in Locally Advanced Head and Neck Squamous Cell Carcinoma

NCT04099290

Head and Neck NeoplasmCarcinoma, Squamous Cell

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RECRUITINGPHASE1

Dose Finding Study of Zanzalintinib With Pembrolizumab and Cetuximab in Head and Neck SCC

NCT06912087

Head and Neck NeoplasmsCarcinoma, Squamous Cell+4 more

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: March 10, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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

Exclusion Criteria

Circulating Tumor DNA (ctDNA) in Locally Advanced Head and Neck Squamous Cell Carcinoma

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