Purpose: Almost 20% of patients with high-risk locally advanced (LA) cutaneous squamous cell carcinoma (cSCC) treated with standard-of-care surgical resection and adjuvant radiotherapy (RT) experience local disease recurrence within 5 years. The PD-1 inhibitors cemiplimab and pembrolizumab have recently shown antitumor activity and manageable safety in LA or metastatic cSCC. The randomized, double-blind, placebo controlled, phase 3 KEYNOTE-630 (NCT03833167) study will investigate adjuvant pembrolizumab in high-risk LA cSCC.
Methodology: Eligible patients have histologically confirmed LA cSCC with ≥1 high-risk feature, have undergone complete macroscopic resection of all known cSCC disease (with/without microscopic positive margins), and have completed adjuvant RT (≥45 Gy). Patients must be disease free ≤28 days from randomization and have an ECOG performance status of 0/1. Patients are randomly allocated 1:1 to pembrolizumab 400 mg Q6W or placebo for ≤9 cycles (approximately 1 year), until disease recurrence, start of new anticancer treatment, unacceptable toxicity, or withdrawal. Randomization is stratified (yes vs no) by extracapsular extension, cortical bone invasion, and prior systemic therapy. The primary end point is recurrence-free survival per investigator review with biopsy confirmation. Secondary end points are OS, safety, and health-related quality of life. Imaging is performed Q12W until the end of year (EOY) 2, then every 6 months until EOY 5. AEs are monitored throughout the study and ≤30 days after treatment end (90 days for serious AEs) and graded per NCI CTCAE v4.0. Patient-reported outcomes are assessed on day 1 of cycles 1-3, then Q12W until EOY 2. Crossover from placebo to pembrolizumab (≤18 cycles) is allowed if biopsy-proven disease recurrence occurs before EOY 5. Pembrolizumab retreatment (≤18 cycles) is allowed if disease recurs >6 months after completion of 9 pembrolizumab cycles and before EOY 5. Enrollment of ~570 patients is planned.
Conclusion: Recruitment is ongoing in 20 countries.