Neoadjuvant adebrelimab combined with triplet chemotherapy for locally advanced resectable adenocarcinoma of esophagogastric junction: a prospective, single-arm, phase II feasibility and safety study.

Background: Immune checkpoint inhibitors (ICIs) in combination with chemotherapy have become the standard treatment for advanced adenocarcinoma of the esophagogastric junction (AEG). While perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) remains the global standard for locally advanced resectable AEG, its substantial hematologic toxicity and perioperative tolerability concerns may limit broader adoption in some Asian patients in real-world clinical practice. This study aimed to assess the perioperative feasibility and safety of neoadjuvant adebrelimab combined with chemotherapy (nab-paclitaxel, lobaplatin, and S-1) in patients with resectable, locally advanced AEG. Methods: Between November 2023 and April 2025, 24 patients with clinically staged cT3-4aNanyM0 or cT1-2N+M0 resectable AEG were prospectively enrolled at a single center. Patients received two 3-week cycles of neoadjuvant adebrelimab plus nab-paclitaxel, lobaplatin, and S-1, followed by surgery scheduled 4-6 weeks after treatment completion. Survival follow-up was censored on 19 October 2025. The primary endpoint was pathological complete response (pCR) rate. Results: Among the 24 enrolled patients, the median age was 62 years, 83.3% were male, 37.5% had Siewert type III tumors and programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥1. Twenty patients (83.3%) subsequently underwent surgery, all achieving R0 resection. In the intention-to-treat (ITT) population, the pCR and major pathological response (MPR) rates were 16.7% [95% confidence interval (CI): 4.7-37.4%] and 29.2% (95% CI: 12.6-51.1%), respectively. Corresponding rates in the surgery population were 20.0% (95% CI: 5.7-43.7%) and 35.0% (95% CI: 15.4-59.2%). The objective response rate (ORR) was 79.2%, and the disease control rate (DCR) was 100%. At a median follow-up of 9.1 months, the estimated 1-year event-free survival (EFS) and overall survival (OS) rates were 80.8% and 88.9%, respectively. Treatment-related adverse events (TRAEs) were predominantly grade 1-2, with only 1 patient (4.2%) experiencing a grade 3 TRAE. No grade 4-5 TRAEs or treatment-related deaths occurred. There was 1 patient (5.0%) who experienced a grade 3 surgical complication. Conclusions: Neoadjuvant adebrelimab combined with triplet chemotherapy demonstrated acceptable perioperative feasibility, manageable toxicity, and preliminary pathological antitumor activity in patients with locally advanced AEG. Given the exploratory single-arm design and short follow-up, the findings should be considered hypothesis-generating and require validation in larger multicenter randomized trials.