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

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.