34762 Adjuvant Pembrolizumab Versus Placebo in High-Risk Locally Advanced Cutaneous Squamous Cell Carcinoma: the Phase 3 KEYNOTE-630 Study

Purpose: Among patients with high-risk locally advanced (LA) cutaneous squamous cell carcinoma (cSCC), an estimated 20% experience local disease recurrence ≤5 years after standard-of-care surgical resection and adjuvant radiotherapy. KEYNOTE-630 (NCT03833167) is a randomized, double-blind, phase 3 study designed to investigate adjuvant pembrolizumab in high-risk LA cSCC. Design: Eligible patients will have histologically confirmed LA cSCC with ≥1 high-risk features, have completed adjuvant radiotherapy ≥4 weeks and ≤16 weeks from randomization, undergone complete macroscopic resection of all known cSCC disease, and received an adequate postoperative dose of radiotherapy. Patients are required to provide tumor tissue for PD-L1 testing and have an ECOG performance status of 0 or 1. Patients will be randomly allocated 1:1 to receive pembrolizumab 400 mg Q6W or matching placebo for up to 9 cycles or until recurrence of disease, intolerable toxicity, initiation of new anticancer treatment, or patient withdrawal. Randomization will be stratified by extracapsular extension, cortical bone invasion, and prior systemic therapy (all assessed yes vs no). The primary end point is recurrence-free survival, per investigator review with biopsy confirmation. Overall survival, safety, and health-related quality of life are the secondary end points. Adverse events, graded in severity per NCI CTCAE v4.0, will be monitored throughout the study and for 30 days after treatment end. Patient-reported outcomes will be assessed on day 1 of cycles 1 to 3, and then Q12W until the end of year 2. Planned enrollment is ∼570 patients. Recruitment is currently ongoing in 20 countries.