Neoadjuvant cemiplimab plus cetuximab prior to salvage surgery for recurrent oral cavity squamous cell carcinoma.

Abstract

TPS6136 Background: Locoregional recurrence of oral cavity squamous cell carcinoma (OCSCC) after curative-intent therapy remains a major cause of morbidity and mortality. Salvage surgery is the standard of care when feasible but is associated with substantial functional impairment. The combination of PD-1 blockade and EGFR inhibition has demonstrated promising activity in the recurrent/metastatic setting. We hypothesize that the combination of cemiplimab and cetuximab will elicit a robust antitumor response in patients with resectable recurrent OCSCC that will lead to improved clinical outcomes. Methods: This is an open-label, single-center, phase II trial designed to assess the efficacy and safety of cemiplimab plus cetuximab in patients with recurrent, resectable OCSCC irrespective of PD-L1 status (NCT06448026). Key eligibility criteria include histologically confirmed locoregional recurrence at least 3 months after prior curative-intent therapy, including surgery and postoperative radiation, ECOG performance status 0–1, measurable disease per RECIST v1.1, and adequate organ function. Eligible participants receive neoadjuvant cemiplimab 350 mg intravenously every 3 weeks for two cycles combined with weekly cetuximab (loading dose 400 mg/m² followed by 250 mg/m² for up to 6 weeks), followed by salvage surgery. Patients achieving ≥50% pathologic tumor response are eligible to receive adjuvant cemiplimab for up to one year. Blood and tumor tissue for correlative analyses are collected at baseline, during treatment, and at the time of surgery. The primary endpoint is the rate of pathologic tumor response ≥50% (pTR-2) assessed in the surgical specimens local and/or regional. Secondary endpoints include objective response rate per RECIST v1.1, pathologic response rate, disease-free survival, overall survival, and safety. The planned sample size is 17 patients based on a Simon two-stage design. The study is active and accruing; to date, 9 of 17 planned patients have been enrolled. Clinical trial information: NCT06448026 .