Multicenter phase 2 trial of chemotherapy-free neoadjuvant camrelizumab plus apatinib for resectable HNSCC

A phase 2 trial in China and Australia evaluated efficacy, safety, and tumor microenvironment remodeling with neoadjuvant camrelizumab plus apatinib in resectable head and neck squamous cell carcinoma (HNSCC; stages II-IVA). In this trial, 41 patients with resectable HNSCC were randomized 2:1 to receive one cycle (n=26) or two cycles (n=15) of camrelizumab 200 mg intravenously plus apatinib 250 mg orally for 21 days per cycle. Primary endpoints were safety and major pathologic response (MPR) rate. All 41 patients completed treatment and underwent R0 resection without surgical delay. The overall MPR rate was 29.3%, with 40% in the two-cycle group and 23.1% in the one-cycle group (p=0.300). Grade 3 or higher treatment-related adverse events occurred in one patient (2.4%). MPR was significantly associated with PD-L1 combined positive score ≥ 20% (50% versus 13%; p=0.023) and post-neoadjuvant circulating tumor cell clearance (87.5% versus 36.8%; p=0.033). Multiplex immunofluorescence (mIF) revealed coupled vascular normalization, hypoxia relief, and immune reprogramming in MPR patients, with vascular maturation quantitatively coupled to immune infiltration. The authors conclude that neoadjuvant camrelizumab plus apatinib demonstrated promising pathologic activity and tolerability in resectable HNSCC. PD-L1 CPS, CTC clearance, and mIF-based tumor microenvironment profiling warrant investigation as candidate predictive biomarkers.