Adebrelimab combined with albumin-paclitaxel and nedaplatin as neoadjuvant therapy for locally advanced resectable esophageal squamous cell carcinoma: A multicenter, single-arm, phase II clinical study.

Abstract

410 Background: Adebrelimab is a high-affinity humanized anti-PD-L1 monoclonal antibody that has shown efficacy and a favorable safety profile in advanced esophageal squamous cell carcinoma (ESCC) and extensive-stage small-cell lung cancer. In this study, we aim at exploring the feasibility and safety of adebrelimab in combination with albumin-bound paclitaxel and nedaplatin as neoadjuvant therapy for patients with locally advanced, resectable ESCC. Methods: This multicenter, single-arm, phase II study enrolled patients with histologically confirmed, locally advanced resectable ESCC (clinical stage IIa–IIIb), who had not received prior systemic therapy. Participants had an ECOG performance status of 0–1 and adequate organ function. Treatment regimen consisted of adebrelimab (1200 mg, iv, q3w) plus albumin-paclitaxel (260 mg/m², iv, q3w) and nedaplatin (75 mg/m², iv, q3w) for three cycles. Tumor response was assessed per RECIST v1.1. Radical surgery was performed within 4-8 weeks after the last dose. The primary endpoint was pathological complete response (pCR). Secondary endpoints included R0 resection rate, major pathological response, objective response rate (ORR), disease control rate (DCR), disease-free survival, overall survival, and safety. Results: As of September 2025, seventeen patients were enrolled for efficacy analysis, of which 11 patients achieved partial response and 6 had stable disease, resulting in an ORR of 64.7% and a DCR of 100%. Seventeen patients completed surgery, and all achieved R0 resection. The median interval between the last dose and surgery was 42 days (range, 28-69 days), the median duration of surgery was 340 minutes (range, 205-430 minutes), the median intraoperative blood loss was 100 ml (range, 50-400 ml), and the median postoperative hospital stay was 8 days (range, 6-12 days). Postoperative pathological analysis revealed a pCR rate of 17.6% (3/17). Treatment-related adverse events (TRAEs) were predominantly grade 1-2 and manageable. Common TRAEs included alopecia (78.9%), myalgia (63.2%), paresthesia (36.8%), leukopenia (31.6%), arthritis (31.6%), pruritus (15.8%), fatigue (15.8%), vomiting (10.5%), decreased appetite (10.5%), and rash (10.5%). No grade 3-4 TRAEs were observed. Conclusions: The neoadjuvant therapy with adebrelimab, albumin-paclitaxel and nedaplatin showed encouraging antitumor activity and was well-tolerated in patients with locally advanced resectable ESCC, achieving pCR in a subset of patients. These supportive results warrant further investigation in ongoing phase II studies. Clinical trial information: NCT06508229 .