PF chemotherapy combined with a PD-1/CTLA-4 bispecific antibody as first-line treatment in patients with recurrent/metastatic head and neck squamous cell carcinoma: a prospective, single-arm, phase II clinical study

Abstract

This study evaluated the antitumor activity and safety of cadonilimab, a programmed cell death protein 1 (PD-1)/cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) bispecific antibody, combined with platinum/carboplatin and 5-fluorouracil (PF) chemotherapy as first-line treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). In this prospective, single-arm, phase II trial, patients with histopathologically confirmed R/M HNSCC received cadonilimab (10 mg/kg) plus PF chemotherapy every 3 weeks for 4–6 cycles, followed by maintenance cadonilimab. The primary endpoint was 1-year progression-free survival (PFS). A target sample size of 30 was planned, but the study was terminated prematurely after enrolling 16 patients due to slow accrual. Sixteen patients were enrolled. At a median follow-up of 18.4 months (range, 4.6 - 39.6), the 1-year PFS and overall survival (OS) rates were 50.0% (95% CI: 30.6% - 81.6%) and 75.0% (95% CI: 56.5% - 99.5%), respectively. The Objective Response Rate (ORR) was 56.3% (95% CI: 29.9% - 80.2%). Median PFS and OS were 9.8 months (95% CI: 2.8 - NR) and 17.7 months (95% CI: 12.3 - NR), respectively. Grade ≥3 treatment-related adverse events (TRAEs) occurred in four patients (25%), with no treatment-related deaths or immune-related cardiac toxicities reported. In this exploratory study, first-line cadonilimab combined with PF chemotherapy exhibited potential antitumor activity and manageable safety profiles in patients with R/M HNSCC. Given the favorable baseline profile of the cohort and the single-arm design, these findings should be interpreted with caution. Larger randomized controlled trials are required to determine whether dual PD-1/CTLA-4 blockade offers an incremental benefit over standard anti-PD-1-based regimens.