A phase II study of perioperative cadonilimab (AK104) in patients with recurrent resectable head and neck squamous cell carcinoma.

2529 Background: Salvage surgery is standard of care for patients with recurrent, resectable head and neck squamous cell carcinoma (HNSCC); However, the efficacy of salvage surgery remains limited. Therefore, there is an urgent need to explore new therapeutic strategies to further improve the survival of this patient subset. Cadonilimab, a PD-1/CTLA-4 bispecific antibody, uses an IgG-ScFv structure with Fc domain point mutations, allowing for high retention in tumor tissue, and providing enhanced stability and improved safety. In this study, we aim to explore the efficacy and safety of neoadjuvant and adjuvant Cadonilimab combined with salvage surgery in patients with recurrent, resectable HNSCC. Methods: This was an open-label, single-institutional phase II clinical trial (ChiCTR2400079741). Patients aged 18-75 years, pathologically confirmed recurrent HNSCC (oral, laryngeal, hypopharyngeal, and oropharyngeal carcinoma), and with resectable diseases assessed by surgeons were included. Eligible patients received two cycles of Cadonilimab (6mg/kg, ivgtt, q2w) 2-4 weeks before surgery, then treated by salvage surgery, followed by 12 cycles of adjuvant Cadonilimab. Primary endpoint was 1-year disease free survival (DFS), and secondary endpoints were objective response rate (ORR), major pathological response (MPR), OS and safety. Results: From November 2023 to December 2024, a total of 32 patients were enrolled. One patient refused surgery, and 31 patients were included in the final analysis. According to radiological assessment, the ORR was 28.1% (9/32), with 2 cases of complete response (CR) and 7 cases of partial response (PR). Among the patients receiving surgical resection, the MPR rate was 32.3% (10/31), with 9.7% (3/31) of patients achieving pathological CR. With a median follow-up of 18.8 months (range, 13.0-25.7 months), the 1-year DFS rate was 77.4%, and the 1-year OS rate was 87.1%. Treatment-related adverse events (TRAEs) occurred in 74.2% (23/31) of patients. The majority of TRAEs were grade 1 or 2. Grade ≥3 TRAEs occurred in 6.5% (2/31) of patients, including one case of grade 3 neutropenia and one case of grade 4 immune-related hepatitis. The most common TRAEs were hypothyroidism (25.8%, n=8), anemia (25.8%, n=8), lymphocytopenia (19.4%, n=6), fatigue (16.1%, n=5), myocarditis (12.9%, n=4), constipation (12.9%, n=4), rash (12.9%, n=4), elevated ALT/AST levels (12.9%, n=4), and neutropenia (6.5%, n=2). Conclusions: Cadonilimab demonstrated encouraging anti-tumor activity and acceptable safety profile in patients with recurrent, resectable HNSCC. Cadonilimab may change the therapeutic approach for recurrent, resectable HNSCC. Clinical trial information: ChiCTR2400079741.