A phase III, randomised, double-blind study of adjuvant cemiplimab versus placebo post-surgery and radiation in patients with high-risk cutaneous squamous cell carcinoma (CSCC)

Abstract

Background: CSCC is the second most common skin cancer. While the surgical cure rate for CSCC is > 95%, a proportion of pts are considered to have high-risk for recurrence as assessed by immune status, primary disease stage, extent of nodal involvement, presence of extracapsular extension, and prior treatment. Post-operative RT is recommended for pts with high-risk features, but relapse with locoregional recurrence or distant metastases may still occur. This study evaluates the efficacy of cemiplimab, a human anti–PD-1 monoclonal antibody, as an adjuvant therapy for pts with CSCC with high-risk features, after surgery and RT. Trial design: This randomised, placebo-controlled, double-blind, multicentre, Phase III study will evaluate cemiplimab as an adjuvant treatment for pts with high-risk CSCC, based on surgical and clinicopathologic findings, who have completed surgery and post-operative RT. Immunocompromised pts were excluded. The trial will enrol 412 pts from about 100 sites in North America, Europe, and Asia-Pacific regions. Pts with at least one of the following high-risk features are eligible: a) nodal disease with extracapsular extension b) in-transit metastases c) T4 lesion d) perineural invasion and e) recurrent CSCC with at least one other risk factor. In Part 1 (blinded), pts will be randomised 1:1 to receive 350 mg cemiplimab or placebo intravenously every 3 weeks (Q3W) for up to 48 weeks. In optional Part 2 (unblinded), pts in the placebo arm who experience disease recurrence or pts in the cemiplimab arm who experience disease recurrence ≥3 months after completion of 48-week treatment in Part 1 will be eligible to receive open-label 350 mg Q3W cemiplimab for up to 96 weeks. Key objectives are to compare disease-free survival (primary) as well as overall survival, freedom from locoregional relapse, and distant relapse (secondary) of adjuvant cemiplimab vs placebo in pts with high-risk CSCC. Editorial acknowledgement: Medical writing support and typesetting was provided by Bu Reinen of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc., and Sanofi. Legal entity responsible for the study: Regeneron Pharmaceuticals, Inc., and Sanofi. Funding: Regeneron Pharmaceuticals, Inc., and Sanofi. Disclosure: D. Rischin: Research grant / Funding (institution), Non-remunerated activity/ies: Regeneron Pharmaceuticals, Inc.; Research grant / Funding (institution), Non-remunerated activity/ies: GSK; Research grant / Funding (institution), Travel…