Phase II study of neoadjuvant cemiplimab prior to surgery in patients with stage III/IV (M0) cutaneous squamous cell carcinoma of the head and neck (CSCC-HN)

Background Cutaneous squamous cell carcinoma (CSCC) harbors a high tumor mutation burden (TMB) due to ultraviolet light-mediated DNA damage, and are highly immune-responsive. Cemiplimab, a monoclonal antibody directed against programmed death 1 (PD-1), is approved by the FDA and EMA as treatment for advanced CSCC patients who are not candidates for curative surgery. Here we explore the efficacy of neoadjuvant cemiplimab in CSCC- head and neck (HN) patients for whom surgery and radiation was planned. Methods Patients with stage III/IV (M0) (AJCC 8th Ed) CSCC-HN were treated with 2 doses of cemiplimab 350 mg intravenously every 3 weeks prior to surgery. The primary endpoint was overall response rate (ORR) per RECIST v1.1. Secondary endpoints included pathologic response rate, safety and tolerability, and analysis of candidate biomarkers from pre- and post-treatment blood and tumor specimens. Results Twenty patients (18M, 2F) enrolled with median age 69 years (range: 42-88) and stage III (n = 8) or IV (n = 12) disease. Seven (35%) patients experienced grade 1 or 2 adverse events (AEs); 6 (30%) grade 1 rash/pruritis, 1 (5%) grade 2 myalgia, and 1 (5%) grade 2 fatigue. There were no grade ≥ 3 AEs and no surgical delays. ORR by RECIST was 30% (6 partial response, 12 stable disease, 2 progressive disease). Pathologic complete response (pCR) was observed in 11 (55%) patients and major pathology response (MPR, ≤ 10% viable tumor) in an additional 3 (15%) patients. TMB and PD-L1 expression analyses in pre-treatment samples are in process. Eleven (55%) patients did not receive planned radiotherapy after surgery based on the pathologic responses. No recurrences have been observed with a median follow up of 3.8 months (range: 1.5-11.2). Conclusions Neoadjuvant cemiplimab was well-tolerated and induced a pCR or MPR in 70% of stage III/IV (M0) CSCC patients. A multicenter phase II study is planned to confirm these results and to describe the ability of neoadjuvant cemiplimab to allow less extensive treatment. Clinical trial identification NCT03565783. Legal entity responsible for the study The University of Texas MD Anderson Cancer Center. Funding Regeneron. Disclosure N. Gross: Advisory / Consultancy, Research grant / Funding (self): Regeneron; Advisory / Consultancy: PDS Biotechnology; Advisory / Consultancy: Intuitive Surgical. B.S. Glisson: Research grant / Funding (institution): Pfizer; Research grant / Funding (self): ISA Pharmaceuticals. All other authors have declared no conflicts of interest.