Phase 1 study of induction chemoimmunotherapy (ICI) with cemiplimab in combination with cisplatin and docetaxel (TPI) in locally advanced squaous cell carcinoma of the head and neck (LA SCCHN).

e18085 Background: Despite advances in therapy, overall survival for locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) remains suboptimal, with 5-year survival rates depending on HPV status which indicates a need for additional therapeutic approaches. We sought to improve outcomes by adding immunotherapy to induction chemotherapy with cisplatin and docetaxel (TP). ICI potentially is a less toxic and more efficacious alternative to traditional chemotherapy induction regimens. Methods: In this phase 1, non-randomized study (NCT05376553), patients with previously untreated stage IV LA SCCHN were enrolled into two cohorts. Cohort A received cisplatin (100 mg/m²) and docetaxel (75 mg/m²) on day 1 followed by cemiplimab (350 mg) on day 14 for three cycles; Cohort B received cemiplimab every 3 weeks starting on day −7. Patients then underwent standard-of-care surgery and/or concurrent chemoradiation, followed by adjuvant cemiplimab every 3 weeks for eight cycles. Cemiplimab was combined with TP using a standard 3+3 design without dose escalation. Dose-limiting toxicities attributable to cemiplimab were assessed in cycle 1. Twenty-four patients were enrolled with primary tumors in the oropharynx (15; HPV+ 9), larynx (2), oral cavity (3), nasopharynx (1; HPV+), and hypopharynx (3). Results: 24 eligible patients-initiated therapy and all completed ICI and have completed the study.1 death occurred during follow up period unrelated to study drug or disease. 2 deaths due to progression of disease; 4 patients experienced progression of disease, and 1 patient was lost to follow up. 16/24 (67%) of patients who completed the study remain alive in remission. Of among the 24 patients, that completed ICI the overall response rate (ORR) was 83.33% with 4 partial responses, 14 complete responses, and 6 progressions of disease. The disease control rate is 83.33%, with a relapse rate of 18.18%. 5/5 oral cancer patients underwent resection, 3 had complete pathological response, 1 with 85% pathological tumor necrosis and 1 had a minimal pathological response <10%. There was no dose limiting toxicities The median duration follow-up was 21 months. Conclusions: Induction with ICI with cemiplimab combined with cisplatin and docetaxel was feasible and demonstrated an acceptable safety profile in patients with LA SCCHN, indicating a high ORR and disease control rate. These phase I results support further investigation in larger studies. Clinical trial information: NCT05376553 .