Preliminary results of benmelstobart (BEN) combined with concurrent chemoradiotherapy (cCRT) versus cCRT alone as neoadjuvant therapy for esophageal squamous cell carcinoma (ESCC): A multicentre, randomised study.

376 Background: While concurrent chemoradiotherapy (cCRT) remains the standard neoadjuvant therapy for resectable esophageal squamous cell carcinoma (ESCC), pathological complete response (pCR) rates remain suboptimal (20–30%). Immunotherapy has demonstrated efficacy in advanced ESCC, its potential synergy with cCRT in the neoadjuvant setting warrants investigation. Methods: In this multicenter, randomised, phase II trial, we planned to enroll 100 patients with resectable ESCC (T1-3N+M0/T3NanyM0). Participants were randomized 1:1 to receive either anti-PD-L1 antibody benmelstobart (1200mg, D1 and 22) + cCRT (paclitaxel 50 mg/m² + carboplatin AUC2, weekly with radiotherapy 41.4 Gy/23 fractions) or cCRT alone, stratified by cT stage (T1-2 vs T3). Surgery was performed 6-8 weeks post-treatment. The primary endpoint was pCR rate. Secondary endpoints included major pathological response (MPR), objective response rate (ORR), disease control rate (DCR), R0 resection rate, 1-year disease-free survival (DFS), 1-year overall survival (OS), completion rate of neoadjuvant therapy, and safety. A radiation de-escalation (36 Gy) was preplanned if ≥18 of the first 30 patients in BEN +cCRT group achieved pCR. Results: From October 24, 2024, to August 31, 2025, 82 patients were randomly assigned to BEN + cCRT group (n=42) or cCRT group (n=40). Thirty and 36 patients completed neoadjuvant therapy, respectively, while 7 and 4 remain on treatment. Besides, 4 patients withdrew after randomization and 1 patient withdrew without completing neoadjuvant therapy in BEN + cCRT group. Eighteen patients in the BEN +cCRT group and 24 in the cCRT group had undergone esophagectomy with postoperative pathology available. Of them, R0 resection was 100% in both groups. pCR rates were 50% (9/18) versus 42% (10/24), and MPR rates were 78% (14/18) versus 63% (15/24), respectively. Grade ≥3 treatment-related adverse events (TRAEs) were observed in 40% versus 35% of patients, respectively, with hematologic toxicity being the most common. No grade ≥3 radiation esophagitis or grade 5 TEAEs were observed. Conclusions: Neoadjuvant benmelstobart combined with cCRT shows encouraging preliminary efficacy, including high pCR and MPR rates, and a manageable safety profile in resectable ESCC. Continued enrollment and follow-up will further elucidate the regimen’s clinical benefits. Clinical trial information: NCT06637163 .