A phase II trial of chemotherapy-free neoadjuvant camrelizumab plus apatinib for resectable HNSCC: pathological response and vascular-immune crosstalk

Abstract Purpose: To evaluate the efficacy, safety, and tumour microenvironment remodelling of neoadjuvant camrelizumab plus apatinib in resectable head and neck squamous cell carcinoma (HNSCC; stage II–IVA). Materials and Methods: In this single-arm, exploratory phase II trial (ChiCTR2100051989), 41 patients with resectable HNSCC were randomly assigned 2:1 to receive one cycle (n = 26) or two cycles (n = 15) of camrelizumab 200 mg intravenously plus apatinib 250 mg orally daily for 21 days per cycle. Primary endpoints were safety and major pathological response (MPR) rate. Exploratory endpoints included MPR associations with PD-L1 combined positive score (CPS), post-neoadjuvant circulating tumour cell (CTC) clearance, and multiplex immunofluorescence (mIF) characterisation of tumour microenvironment remodelling in 30 paired pre- and post-treatment samples. Results: All 41 patients completed treatment and underwent R0 resection without surgical delay. The overall MPR rate was 12/41 (29.3%), with 40.0% in the two-cycle group versus 23.1% in the one-cycle group (p = 0.300). Grade 3 or higher treatment-related adverse events occurred in 1/41 patients (2.4%). MPR was significantly associated with CPS ≥20 (50.0% vs 13.0%; Benjamini-Hochberg [BH]-adjusted p = 0.023) and CTC clearance (87.5% vs 36.8%; BH-adjusted p = 0.033). mIF revealed coupled vascular normalisation, hypoxia relief, and immune reprogramming in MPR patients, with vascular maturation quantitatively coupled to immune infiltration. Conclusion: Neoadjuvant camrelizumab plus apatinib demonstrated promising pathological activity and tolerability in resectable HNSCC. PD-L1 CPS, CTC clearance, and mIF-based tumour microenvironment profiling warrant investigation as candidate predictive biomarkers.