A Phase III, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Pembrolizumab versus Placebo as Adjuvant Therapy Following Surgery and Radiation of High-Risk Locally Advanced Cutaneous Squamous Cell Carcinoma (LA cSCC) (KEYNOTE-630)

This is a randomized, double-blind, study that compares pembrolizumab 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).

Inclusion Criteria:
• Has histologically confirmed cutaneous squamous cell carcinoma (cSCC) as the primary site of malignancy (metastatic skin involvement from another primary cancer or from an unknown primary cancer is not permitted)
• Has histologically confirmed 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
• Has completed adjuvant radiotherapy (RT) for LA cSCC with last dose of RT ≥4 weeks and ≤16 weeks from randomization
• Has completed at least 50 Gray (Gy) 25 fractions of adjuvant RT for LA cSCC prior to study entry
• Is disease free as assessed by the investigator with complete radiographic staging assessment ≤28 days from randomization
• 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
• Has a life expectancy of >3 months

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 co-stimulatory or co-inhibitory 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 randomization
• Has not recovered from all radiation-related toxicities; has not required corticosteroids; and has not had radiation pneumonitis
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device ≤4 weeks prior to the first dose of study intervention
• Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
• Has an active infection requiring systemic therapy
• Has had an allogeneic tissue/solid organ transplant
Phase III
Oral, Head and Neck
R Bryan Bell, M.D.
George Morris
  • Oncology and Hematology Care Westside
  • Providence Cancer Institute Franz Clinic