Efficacy and safety of toripalimab in combination with cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC): a phase 1b/2 study

This open-label, multicenter, phase 1b/2 trial assessed the safety and efficacy of toripalimab plus cetuximab in patients with platinum-refractory (Cohort A) or previously untreated programmed cell death-ligand 1 (PD-L1)-positive (Cohort B) recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Patients received toripalimab 240 mg intravenously (IV) every 3 weeks and cetuximab (400 mg/m² loading, then 250 mg/m² weekly maintenance). Primary endpoints were safety in phase 1b and objective response rate (ORR) as assessed by the Independent Review Committee (Cohort A) and investigator (Cohort B) in phase 2. Secondary efficacy endpoints included progression-free survival (PFS) and overall survival (OS). By October 25, 2024, 88 patients were enrolled (Cohort A: 45; cohort B: 43). In Cohort A, confirmed ORR was 60.0% (95% confidence interval [CI]: 44.3%, 74.3%), median PFS was 9.9 months (95% CI: 4.2, 19.4), and median OS was 14.1 months (95% CI: 8.5, 17.7). PD-L1-positive (combined positive score [CPS] ≥1) patients appeared to benefit more than PD-L1-negative (CPS < 1) patients (ORR: 64.5% vs. 40.0%, median PFS: 10.4 vs. 4.0 months, median OS: 15.4 vs. 13.3 months). In Cohort B, confirmed ORR was 44.2% (95% CI: 29.1%, 60.1%), median PFS was 8.2 months (95% CI: 4.2, 17.1), and median OS was 18.1 months (95% CI: 10.6, inestimable). Grade ≥3 treatment-emergent adverse events occurred in 53.3% (Cohort A) and 51.2% (Cohort B) of the patients in phase 2. No novel safety signals were identified. Toripalimab combined with cetuximab demonstrated manageable safety and promising efficacy for R/M HNSCC, warranting further investigation. Clinical trial number: NCT04856631.