KEYNOTE-630: Phase 3 Study of Adjuvant Pembrolizumab in High-Risk Locally Advanced (LA) Cutaneous Squamous Cell Carcinoma (cSCC)

Introduction: Durable antitumor activity has been observed with cemiplimab and pembrolizumab in advanced metastatic cSCC. The randomized, double‐blind, phase 3 KEYNOTE‐630 study (NCT03833167) will evaluate adjuvant pembrolizumab in resectable, high‐risk, LA cSCC. Methods: Key eligibility criteria include LA cSCC with ≥1 high‐risk feature: histologically involved nodal disease with extracapsular extension, with ≥1 lymph node >2 cm in diameter or ≥2 lymph nodes involved; any index tumor with ≥2 of the following: tumor ≥4 cm with >6‐mm depth or invasion beyond subcutaneous fat, multifocal perineural invasion for nerves <0.1 mm in diameter (≥3 foci) or any involved nerve ≥0.1 mm in diameter, poor differentiation and/or sarcomatoid and/or spindle cell histology, recurrent disease, satellite lesions and/or in‐transit metastases, lymphatic or vascular involvement; any gross cortical bone, skull base, and/or skull base foramen invasion. Patients must have received adequate postoperative dose of hypofractionated or conventional RT, undergone complete macroscopic resection, and completed adjuvant RT ≥4 and ≤16 weeks from randomization. Patients will be randomly assigned 1:1 to pembrolizumab 400 mg IV Q6W or placebo for ≤9 cycles (1 year). Randomization will be stratified by extracapsular extension, cortical bone invasion, and prior systemic therapy (all, yes vs no). Primary end point: RFS. Secondary end points include OS, HRQoL, and safety. Results: Planned enrolment is ∼570 patients and is ongoing at sites in Asia, Australia, Europe, and North and South America. Conclusions: Results will provide clarity on efficacy and safety of pembrolizumab as adjuvant treatment in patients with high‐risk, LA cSCC.