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 programmed cell death protein 1 (PD-1) /cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) bispecific antibodies may offer synergistic anti-tumor 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 (HNSCC). 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 (DCR), pathological complete response (PCR), major pathological response (MPR), safety, progression-free survival (PFS), and overall survival (OS). 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 patients (90.0%) were male. The ORR was 83.3%, DCR was 100.0%, MPR rate was 76.7% and PCR rate was 50.0%. All patients experienced treatment-related adverse events (TRAEs). Grade 3 TRAEs were reported in 7 (23.3%) patients. PFS and OS 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 macrophage 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 HNSCC.