A phase II study of neoadjuvant cemiplimab in hedgehog inhibitor (HHI)–naive basal cell carcinoma of the head and neck.

Abstract

9515 Background: Surgical resection of locally advanced basal cell carcinoma of the head and neck (BCCHN) often carries significant morbidity. This phase II study seeks to investigate the response to neoadjuvant cemiplimab on surgical morbidity in BCCHN patients. Methods: In this prospective, nonrandomized, multicenter, phase II trial (NCT05929664), anti-PD1 and HHI-naive patients with resectable BCCHN received 2 to 6 cycles of cemiplimab (350mg IV Q21 days), followed by surgical resection or biopsy. Surgical plan at enrollment required functional organ sacrifice (orbit, eyelid, ear, nose, lip, or facial nerve). RECISTv1.1 tumor measurements were performed every 2 cycles to determine primary endpoints of ORR and DCR. Patients with PD (>20% growth) or SD with 5 to 20% growth at any assessment were offered HHI or surgery. Patients with CR at any assessment proceeded to surgery or directed biopsy. Secondary endpoints included: surgical benefit rate (SBR, defined as rate of functional organ preservation, determined by the investigator, comparing surgical resection to surgical plan at time of enrollment), rate of pCR, safety (CTCAEv5.0), and quality of life (FHNSI, FACE-Q and VFQ-25). Correlative studies include examination of the tumor immune microenvironment related to functional changes in immune cell composition. Results: Between August 2023 and September 2025, 33 patients were enrolled: 40-89 yo; 22 M/11 F; sites of disease included eyelid (n=17), orbit (n=4), nose(n=5), lip (n=1), facial nerve (n=1), ear (n=1), and scalp or cheek (n=5). 30 were evaluable: 23 (76.7%) completed 6 cycles. Among the remaining 7 patients, 1 experienced CR after 4 cycles; 1 was taken off therapy for grade 3 myalgia; 1 had SD with 5-20% growth and 2 had PD, and were taken to surgery per protocol; 2 chose surgery due to stagnant response after initial PR. 12 patients (40%) experienced a grade 1-2 treatment-related AE. 1 patient (3.33%) experienced a grade 3 treatment-related AE as above. The ORR was 66.67%. The DCR was 90.0%. Based on RECISTv1.1 criteria, 3.33% (n=1) had CR, 63.33% (n=19) had PR, 23.33% (n=7) had SD, and 10.0% (n=3) had PD as best overall response 8 patients (26.67%) achieved pCR. The SBR was 43.3%, with functional preservation of the eyelid (n=7), nose (n=2), lip (n=1), ear (n=1), or orbit (n=1). Conclusions: Neoadjuvant cemiplimab had an acceptable safety profile and shows promising efficacy in the treatment of advanced, surgically-resectable BCCHN. This novel approach may alleviate the morbidity of subsequent surgical resection. (NCT05929664 supported by Regeneron Pharmaceuticals, Inc.). Clinical trial information: NCT05929664 .