Cadonilimab (a PD-1/CTLA-4 Bispecific Antibody) plus Neoadjuvant Chemotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase II Clinical Trial

Abstract Purpose: Preclinical and clinical findings suggest that PD-1/cytotoxic T lymphocyte–associated protein 4 bispecific antibodies may offer synergistic antitumor activity. This study aimed to explore the efficacy and safety of cadonilimab combined with neoadjuvant chemotherapy in locally advanced, resectable head and neck squamous cell carcinoma. Patients and Methods: Eligible patients were consecutively enrolled and received cadonilimab (10 mg/kg) and chemotherapy (docetaxel, 75 mg/m2 plus cisplatin, 60 mg/m2) every 3 weeks for three cycles. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate, pathologic complete response, major pathologic response (MPR), safety, progression-free survival, and overall survival. Analyses of biomarkers and tumor-infiltrating immune cell subsets were conducted. This study is registered with ClinicalTrials.gov (NCT06023875). Results: Thirty patients were included from July 2023 to December 2023. The median age was 55 years (range: 26–69), and 27 (90.0%) patients were male. The ORR was 83.3%, disease control rate was 100.0%, MPR rate was 76.7%, and pathologic complete response rate was 50.0%. All patients experienced treatment-related adverse events. Grade 3 treatment-related adverse events were reported in 7 (23.3%) patients. Progression-free survival and overall survival data were not yet mature as of the cutoff date (February 1, 2025). Subgroup analysis revealed no significant differences in biomarker expression. A higher baseline infiltration of M1-like macrophages in the tumor stroma was associated with better treatment efficacy. Conclusions: Cadonilimab plus neoadjuvant chemotherapy demonstrated favorable ORR and MPR with manageable toxicities in patients with head and neck squamous cell carcinoma.