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

e18116 Background: To enhance patients' quality of life and prolong their survival, exploring an effective, low-toxicity version of the induction regimen for LA SCCHN is crucial. The addition of immunotherapy to cisplatin and docetaxel (TP) is a less toxic and potentially more effective alternative to the historic chemotherapy induction regimens. Methods: Patients with LA SCCHN were enrolled in a phase 1, NCT05376553, non-randomized study with 2 cohorts. Cohort A received 100 mg/m² cisplatin and 75 mg/m² docetaxel IV on day 1 of each cycle, followed by 350 mg cemiplimab on day 14 for 3 cycles. Cohort B received one additional dose of cemiplimab on D-7. Both cohorts underwent concurrent chemoradiation (CRT) or surgical resection +/- CRT as per standard care. All patients were to receive adjuvant cemiplimab 350 mg every 3 weeks for 8 cycles. With no dose escalation, cemiplimab was given with TP using a standard 3+3 dosing scheme. Dose-limiting toxicity (DLT) was evaluated in the first cycle for the initial 6 patients in each scheduling cohort. Only DLTs related to cemiplimab were considered, excluding known chemotherapy-related adverse events. A total of 24 previously untreated stage IV LA SCCHN patients were enrolled, 21 men and 3 women. Tumors were in the oropharynx (15, HPV + 9/15), larynx (2), oral cavity (3), nasopharynx (1, HPV +), and hypopharynx (3). Results: All 24 eligible patients completed ICI and 17 of 24 patients have completed the study. 7 are still receiving treatment, and 1 death occurred before study drug was given and was not included in the assessment. 16/17 patients who completed the study remain in remission. One patient progressed systemically in the lungs 4 months after radiation, and is undergoing systemic therapy. No DTLs were observed during ICI in all 24 treated patients. Out of the 24 patients that have completed ICI the overall response rate (ORR) to ICI was 87.5% with 12 partial responses, 9 complete responses, 2 stable disease, and 1 progression of disease. The disease control rate is 95.8%, with a relapse rate of 4.2% (1/24). 2/3 oral cancer patients underwent resection, 1 had complete pathological response, 1 with 85% pathological tumor necrosis and 1 pending surgical resection. Median follow-up was 18.06 months (8-29). A full assessment of toxicity with CRT and adjuvant cemiplimab will take place when study treatments are complete. Conclusions: The combination of cemiplimab given with TP appears to be safe and well tolerated in both cohorts. These clinically meaningful findings with high ORR and only one systemic relapse supports the promising role of cemiplimab based ICI for LA SCCHN and may have the potential to be practice-changing if confirmed in larger studies. Clinical trial information: NCT05376553 .