Aims: Treatment options are needed for patients with high-risk, LA cSCC who experience recurrence after surgery. Durable antitumor activity has been observed with cemiplimab and pembrolizumab in advanced metastatic cSCC. The double-blind, phase 3 KEYNOTE-630 study (NCT03833167) is designed to evaluate adjuvant pembrolizumab in resectable, high-risk, LA cSCC.
Methods: 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 undergone complete macroscopic resection, have ECOG PS 0/1, received adequate postoperative dose of hypofractionated or conventional RT, including BED EQD2 >48 Gy, and completed adjuvant RT ≥4 and ≤16 weeks from randomization. Approximately 570 patients will be randomly assigned 1:1 to pembrolizumab 400 mg IV Q6W or placebo for ≤9 cycles (1 year) and stratified by extracapsular extension, cortical bone invasion, and prior systemic therapy (all, yes vs no). Patients receiving placebo may be eligible to cross over to receive pembrolizumab (≤18 cycles) if first biopsy-proven recurrence occurs ≤5 years. In the pembrolizumab arm, eligible patients may receive pembrolizumab retreatment (≤18 cycles). Primary end point: RFS. Secondary end points include OS, HRQoL, and safety.
Results: Enrollment is ongoing at sites in Asia, Australia, Europe, and North and South America.
Conclusions: Results will provide clarity on efficacy and safety of adjuvant pembrolizumab in patients with high-risk, LA cSCC.
Clinical Trial registration: NCT03833167