Penpulimab (AK105) combined with cetuximab as first-line treatment in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC): A phase II clinical trial.

6029 Background: Combination therapy with PD-1 and EGFR inhibitors has shown promising efficacy in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). This open-label, single-arm, multicenter phase II study aimed to evaluate the efficacy and safety of penpulimab (an anti-PD-1 monoclonal antibody) plus cetuximab as first-line treatment in this patient population (NCT05260671). Methods: Eligible patients had R/M HNSCC with no prior immunotherapy or EGFR inhibitor exposure. Participants were either treatment-naïve for systemic therapy or had received platinum-based neoadjuvant/adjuvant or chemoradiotherapy more than 6 months before enrollment. All patients received cetuximab 500 mg/m² intravenously as a lead-in dose on day –14, followed by cetuximab 500 mg/m² plus penpulimab 200 mg intravenously on days 1 and 15 of each 28-day cycle. The primary endpoint was objective response rate (ORR) per RECIST v1.1. Secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Results: Between March 15, 2022, and January 19, 2026, 31 patients were enrolled. The median follow-up was 20.13 months (95% CI: 15.6–NA). Of these, 29 patients were evaluable for efficacy. The ORR was 44.8% (13/29), and the DCR was 82.8% (24/29). Four patients (13.8%) achieved a complete response (CR). The median DOR was 12.1 months (95% CI: 6.13–NA). For the entire cohort, median PFS was 6.0 months (95% CI: 4.3–18.3), with a 12-month PFS rate of 35.6%. Median OS was 29.1 months (95% CI: 18.2–NA), and the 12-month OS rate was 72.4%. Treatment-related adverse events (TRAEs) occurred in 29 patients (93.5%). Grade ≥3 TRAEs were observed in 4 patients (12.9%), including acneiform rash (6.5%), anemia (3.2%), and oral mucositis (3.2%). No fatal TRAEs were reported. Conclusions: The combination of penpulimab and cetuximab demonstrated favorable clinical efficacy and a manageable safety profile in patients with R/M HNSCC, supporting its potential as a first-line treatment option. Trial Registration: NCT05260671. Ethics Approval: This study was approved by the Ethics Committee for Drug Clinical Trials of the Eye & ENT Hospital of Fudan University (Approval No. [20211141-1], 2022). All participants provided written informed consent prior to enrollment. Clinical trial information: NCT05260671 .