Updated results of benmelstobart combined with anlotinib and chemotherapy as neoadjuvant therapy for locally advanced head and neck squamous cell carcinoma: A single-arm, open-label phase II clinical trial.

Abstract

6045 Background: Locally advanced head and neck squamous cell carcinoma (HNSCC) is characterized by high risks of local recurrence and distant metastasis, resulting in poor prognosis. Neoadjuvant therapy has the potential to improve survival outcomes in these patients. This study aimed to evaluate the safety and efficacy of benmelstobart in combination with anlotinib and chemotherapy as neoadjuvant therapy for resectable locally advanced HNSCC. Preliminary results were presented at the 2025 ESMO Congress (Abstract 1454eP), and updated consecutive results are reported herein. Methods: This single-center, phase II clinical trial enrolled patients with stage III/IVA HNSCC who met predefined eligibility criteria. Patients underwent neoadjuvant therapy with benmelstobart (1200mg), anlotinib (10mg), cisplatin (60mg/m²), and nab-paclitaxel (125mg/m², d1, d8) for three 21-day cycles. Surgical resection was performed within two weeks after neoadjuvant therapy completion, with tumor specimens collected for pathological evaluation. The primary endpoint was major pathological response (MPR) rate. Postoperative adjuvant therapy was administered based on risk assessment. Secondary endpoints included objective response rate (ORR), pathological complete response (pCR) rate, 2-year disease-free survival (DFS), 2-year locoregional recurrence-free survival (LRFS), 2-year distant metastasis-free survival (DMFS), 2-year overall survival (OS), and safety assessment. Results: As of Jan 9, 2026, a total of 36 patients who met the inclusion and exclusion criteria were enrolled. The median age was 61 years (range: 38-77), with males accounted for 91.7%. ECOG performance status 0 was observed in 80.5% of patients, and hypopharyngeal carcinoma was the most common primary tumor site (50.0%). Stage III and IVA disease accounted for 25.0% and 75.0% of patients, respectively. At the data cut-off date, 32 patients completed neoadjuvant therapy, achieving an ORR of 96.9% and a disease control rate (DCR) of 100%. Among them, 27 patients underwent surgery and completed histopathological assessment. MPR was achieved in 23 cases (including 20 with pCR), resulting in an MPR rate of 85.2% (95%CI: 66.3%-95.8%). The incidence of all grade treatment-emergent adverse events (TEAEs) was 86.1% (31/36). The incidence of grade≥3 TEAEs was 8.3% (3/36), most commonly myelosuppression (5.6%) and renal impairment (2.8%). Conclusions: The combination of benmelstobart, anlotinib, and chemotherapy demonstrated promising efficacy as neoadjuvant therapy for resectable HNSCC, with high ORR and MPR rates, along with an acceptable safety profile. These updated results support further evaluation of this combination in randomized controlled trials. Clinical trial information: NCT0669949 .