Adebrelimab with or without induction chemotherapy followed by concurrent chemoradiotherapy for unresectable locally advanced esophageal squamous cell carcinoma (RICE): A prospective, phase 2 trial.

Abstract

314 Background: The prognosis for locally advanced esophageal squamous cell carcinoma (LAESCC) remains poor.This study aims to investigate the efficacy and safety of Induction immunotherapy in unresectable LAESCC. Methods: RICE is a prospective, two-arm clinical study. Patients aged 18–70 years with untreated, unresectable LAESCC.Patients with CPS >20 received adebrelimab (Ade), while those with CPS ≤20 received adebrelimab plus induction chemotherapy (Ade+IC). Subsequently, both groups received concurrent chemoradiotherapy (CRT) combining weekly paclitaxel plus platinum with radiotherapy (50 Gy in 25 fractions). The primary endpoint was clinical complete response rates (cCR rate) at 3 months after radiotherapy. The secondary endpoints were overall survival (OS), progression free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR), completion rate of concurrent radiotherapy and safety. All enrolled patients were included in the efficacy and safety analyses. Predictive biomarkers were explored using single-cell sequencing and whole-exome sequencing. The trial was registered at ClinicalTrials.gov (identifier: NCT06510660) and is currently under enrollment. Results: Between Apr 11, 2024, and Sept 3, 2025, 22 patients staged III or IV were enrolled with an median age of 63 years (interquartile range, 49–70). 21 patients completed induction therapy with 1 discontinued treatment and 1 withdrawal. At the end of induction therapy, no complete response was observed, and ORR was 33.3% in the Ade group versus 21.4% in the Ade+IC group (95% confidence interval[CI], 0.110-22.859; P=0.613). Among 19 (86.4%) patients who completed the planned CRT, the median follow-up time was 7.6 months (range, 2.2–15.8 months). At 3 months after CRT, 4(33.3%; 95% CI, 13.8–60.9) of 12 patients reached complete response and the ORR was 50.0% in the Ade and 75.0% in the Ade+IC group (95% CI, 0.015-8.315; P=0.548). The most common adverse events (AEs) were leukopenia, anemia, neutropenia and thrombocytopenia. Grade 3–5 adverse events were similar. One patient died from esophageal fistula. Conclusions: The addition of induction therapy to CRT is safe and feasible in LAESCC. Immunotherapy monotherapy induction therapy has demonstrated encouraging activity and acceptable toxicity in patients with high PD-L1 expression. Clinical trial information: NCT06510660 .