Neoadjuvant tislelizumab with afatinib for locally advanced head and neck squamous cell carcinoma (neoCHANCE-1): a phase 2 clinical trial

作者：Zhigong Wei, Huijiao Chen, Dejuan Wang, Zheng Jiang, Yiyan Pei, Le-Yu Li, Feng Wang, Jing Jin, Z. Liu, Fei Chen, Jun Li, Xingchen Peng · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-63978-y · 被引用次数：2 · 研究领域：Head and Neck Cancer Studies、Lung Cancer Treatments and Mutations、Cancer Immunotherapy and Biomarkers

Despite receiving standard treatments, patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) often still face significant risks of disease recurrence or metastasis. In this phase II neoCHANCE-1 study (NCT05517330), we evaluated the efficacy and safety of the dual-targeted blockade of the PD-1 and EGFR pathways in a neoadjuvant setting. The primary endpoint was the major pathological response (MPR) rate. The secondary endpoints included the pathological complete response (pCR) rate, overall response rate (ORR), safety, disease-free survival (DFS), and overall survival (OS). A cohort of 25 patients was subjected to a treatment regimen consisting of tislelizumab for two cycles, concomitant with daily intake of afatinib for six weeks. Among the 23 evaluable patients, eight (35%; 95% CI, 16%–57%) achieved an MPR that met the prespecified endpoint, and four (17%, 95% CI, 5%–39%) achieved a pCR of the primary tumor. The ORR was 48% (12/25, 95% CI: 28%–69%). The most common grade 3–4 adverse events included diarrhea (5/25), hypokalemia (4/25), and rash (3/25). This study highlights the encouraging antitumor activity, manageable toxicity profile, and promising immune activation caused by neoadjuvant tislelizumab plus afatinib treatment of HNSCC, which deserves further investigation. Immunotherapy has improved patient outcomes in those with metastatic or recurrent head and neck squamous cell carcinoma (HNSCC) but less so in the neoadjuvant setting. Here, the a...