Abstract 460TiP
Background
The efficacy and safety of neoadjuvant immunotherapy (NAI) for treating resectable locally advanced head and neck squamous cell carcinoma (LAHNSCC) remain unclear, and the comprehensive protocol of NAI needs further exploration. Current evidence suggests that PD-1 inhibitor combined with chemotherapy showed promising efficacy, but most treatment regimens primarily focus on single-target inhibitors. Notably, studies have shown that the dual inhibition of combination PD-1 and CTLA4 or PD-1 and VEGF brought superior efficacy than PD-1 inhibitor monotherapy in LAHNSCC. This study aims to compare the efficacy and safety of single-target and double-target immunotherapy combined with chemotherapy in the treatment of resectable LAHNSCC, to explore the optimal neoadjuvant immunotherapy strategy.
Trial design
This randomized, controlled, open label, phase II clinical trial will enroll LAHNSCC patients eligible for surgery. Eligible patients will be randomized in a 1:1:1 ratio to either the ivonescimab (PD-1/VEGF bispecific antibody, 10 mg/kg intravenously every 3 weeks) in combination with cisplatin and nab-paclitaxel (Cohort 1), or the cadonilimab (PD-1/CTLA-4 bispecific antibody, 6 mg/kg intravenously every 3 weeks) in combination with cisplatin and nab-paclitaxel (Cohort 2), or the penpulimab (PD-1 antibody, 200 mg intravenously every 3 weeks) in combination with cisplatin and nab-paclitaxel (Cohort 3). Dose adjustments are allowed based on toxicity, and surgery will be performed within 2-4 weeks after 3 cycles of neoadjuvant treatment. For pathological complete response (pCR), patients exempted from radiotherapy and receive adjuvant ivonescimab/cadonilimab/penpulimab for 16 cycles. For no pCR, patients will receive subsequent adjuvant radiotherapy or chemoradiotherapy based on risk factors after surgery. Once radiotherapy/ chemoradiotherapy is complete, these patients will receive adjuvant ivonescimab/cadonilimab/penpulimab for 16 cycles. The primary endpoints were pCR and safety, with the second primary points focusing on event free survival (EFS) and biomarkers of response or progression.
Clinical trial identification
NCT06444009.
Legal entity responsible for the study
West China Hospital.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.