Neoadjuvant immunotherapy combined with concurrent chemoradiotherapy for locally advanced esophageal squamous cell carcinoma: A prospective, single-arm, phase II trial.

e16095 Background: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). In the era of immunotherapy, it is worth exploring whether the combination of CCRT and immunotherapy can improve efficacy. This study aimed to evaluate the efficacy and safety of preoperative anti-PD-L1 Immunotherapy combined with CCRT in ESCC. Methods: In this phase II trial, patients (pts) with resectable, locally advanced ESCC received neoadjuvant durvalumab (1500mg, Q4W) combined with CCRT (41.4Gy/23f with weekly paclitaxel/carboplatin), followed by surgery. Co-primary endpoints were the objective response rate (ORR, irRECIST) and pathologic complete response (pCR, CAP). Secondary endpoints included safety, surgical outcomes, disease-free survival (DFS), and overall survival (OS) (NCT04568200). Results: As of January 26, 2026, 34 pts were enrolled. Among the 27 pts who completed neoadjuvant therapy and were evaluable for efficacy, the ORR was 88.9% (comprising 1 complete, 22 partial responses, 3 stable disease and 1 progression disease), and the disease control rate (DCR) was 96.3%. The neoadjuvant therapy was completed in a median of 32 days. The regimen was manageable, with 24 pts (90.3%) completing the full radiotherapy course, and all pts completing two cycles of immunotherapy. The median interval from the completion of radiotherapy to surgery was 51.5 days. Of the 27 evaluable patients, 23 were deemed eligible for surgery. Ultimately, 22 pts underwent McKeown minimally invasive esophagectomy, all of whom achieved R0 resection. Pathologic assessment of these surgical specimens showed a primary tumor pCR rate of 50% (11/22) and a pCR rate in both primary tumor and lymph nodes (ypT0N0) of 36.4% (8/22). The major pathologic response (MPR) rate was 72.7% (16/22). The median number of lymph nodes harvested was 44 (range, 25-63). At a median follow-up of 10.7 months, the estimated 1-year DFS rate was 86.3% in the surgical cohort (n=22), and the 1-year OS rate was 97.1% in the intention-to-treat population (n=34). Common AEs included leukopenia/neutropenia (n=14), radiation esophagitis (n=7), pneumonia (n=2), intestinal obstruction(n=1), myocardial infarction due to coronary heart disease (n=1). Two patients contracted COVID-19. No new safety signals were identified. Conclusions: Anti-PD-L1 Immunotherapy combined with CCRT in locally advanced ESCC might be a useful treatment option with highly promising efficacy and manageable safety. Clinical trial information: NCT04568200 .