Phase 3 trial of adjuvant cemiplimab (cemi) versus placebo (pbo) for high-risk cutaneous squamous cell carcinoma (CSCC).

Abstract

6001 Background: Cemiplimab is standard of care for treatment of patients (pts) with advanced (metastatic/unresectable) CSCC. There is no approved systemic treatment for pts with CSCC at high risk of recurrence after definitive local therapy. Methods: C-POST, a double-blind, multicenter, phase 3 study (NCT03969004), enrolled pts with local and/or regional CSCC, after surgery and post-operative radiation therapy, deemed to be at high risk of recurrence due to nodal (extracapsular extension with largest node ≥2 cm or ≥3 involved lymph nodes) and/or non-nodal (in-transit metastases, T4 lesion, perineural invasion, or locally recurrent tumor with ≥1 additional risk feature) criteria. Pts were randomized 1:1 to cemi 350mg or pbo every (Q) 3w for 12w, then cemi 700mg or pbo Q6W up to 36w (up to 48w total). Original protocol had cemi 350mg or pbo Q3W up to 48w. Crossover was allowed after disease recurrence. Primary endpoint was disease-free survival (DFS). Secondary endpoints included freedom from local-regional recurrence (FFLRR), freedom from distant recurrence (FFDR), overall survival (OS), and safety. Data cutoff for pre-specified interim analysis 1 (IA1; ~50% of final DFS events) was Oct 4, 2024. Per IDMC, the pre-specified threshold for DFS was crossed at IA1. Results: From Jun 2019 to Aug 2024, 415 pts (209/206 cemi/pbo) were randomized: median age, 71 yrs (range 33–95); 84% male; 83% head and neck primary; 58%/42% high-risk nodal/non-nodal categories. Median follow-up was 24 mos (range 2–64). DFS was superior with cemi vs pbo: hazard ratio (HR) 0.32 (95% CI 0.20–0.51); p<0.0001 (Table). Estimated 24-mo DFS was 87% (95% CI 80–92) for cemi and 64% (56–71) for pbo. Cemi improved FFLRR (HR 0.20; 95% CI 0.09–0.40) and FFDR (HR 0.35; 0.17–0.72) vs pbo. At IA1, OS HR for cemi vs pbo was 0.86 (95% CI 0.39–1.90). Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 23.9% and 14.2% and discontinuations due to TEAEs occurred in 9.8% and 1.5% of pts receiving cemi and pbo, respectively. In exploratory analyses, DFS benefits were observed in pts with tumoral PD-L1 ≥1% (HR 0.28; 95%CI 0.15–0.52; n=309) and <1% (HR 0.32; 0.12–0.86; n=85). Conclusions: Cemiplimab is the first systemic therapy to demonstrate a statistically significant and clinically meaningful reduction in disease recurrence as adjuvant therapy for high-risk CSCC, and has an acceptable safety profile in this setting. Clinical trial information: NCT03969004 . Cemin=209 Pbon=206 Pts with DFS event, n (%) a 24 (12) 65 (32) Disease recurrence 18 (9) 61 (30) Death 6 (3) 4 (2) DFS, mos, median (95% CI) b NR (NE–NE) 49.4 (48.5–NE) HR (95% CI) c 0.32 (0.20–0.51) - 2-sided p-value d < 0.0001 - 24-mo DFS, % (95% CI) b 87.1 (80.3–91.6) 64.1 (55.9–71.1) 24-mo FFLRR, % (95% CI) b 94.6 (89.1–97.3) 76.7 (69.1–82.6) 24-mo FFDR, % (95% CI) b 94.3 (89.0–97.1) 83.8 (76.3–89.0) NE, not estimable; NR, not reached. a Censored pts: 185 cemi; 141 pbo. b Kaplan-Meier estimate. c Stratified Cox model. d Stratified log-rank test.