Neoadjuvant Short-Course Radiotherapy Plus Tislelizumab and Chemotherapy for Locally Advanced Resectable Esophageal Squamous Cell Carcinoma

Summary

Neoadjuvant Short-Course Radiotherapy Followed by Tislelizumab Plus Chemotherapy for Locally Advanced Resectable Esophageal Squamous Cell Carcinoma This is a prospective, randomized, two-arm, parallel-group, multicenter, exploratory Phase II clinical trial. It aims to evaluate the efficacy and safety of neoadjuvant short-course radiotherapy followed by tislelizumab combined with chemotherapy in participants with locally advanced resectable esophageal squamous cell carcinoma (ESCC). Eligible participants will be randomized in a 1:1 ratio to receive either low-dose or high-dose short-course radiotherapy, followed by tislelizumab, nab-paclitaxel, and carboplatin for 3 cycles. Surgery will be performed 4-6 weeks after the last neoadjuvant treatment. Primary endpoint: Pathological Complete Response (pCR) rate. Secondary endpoints: Major Pathological Response (MPR) rate, Objective Response Rate (ORR), R0 resection rate, downstaging rate, 3-year Event-Free Survival (EFS), 3-year Overall Survival (OS), safety profile, and quality of life. Approximately 50 participants will be enrolled. Randomization will be stratified by tumor location, clinical T stage, and clinical N stage using a stratified block design via an EDC/IWRS system.

Timeline

Start

2026-07-10

Primary completion

2028-01-31

Completion

2029-06-30

Publications

• Results Li C, Han Y, Zhao S, Kang X, Zheng Y, Cao Y, Yan Y, Shi L, Wang X, Lu T, Zou G, Li H, Che J, Xiang J, Zhu L, Hang J, Zhang Y, Jin R, Han D, Chen X, Jing H, Guo W, Cheng Z, Zhao L, Chen X, Yu B, Li J, Li B, Li Y, Li H. Preoperative pembrolizumab (anti-PD-1 antibody) combined with chemoradiotherapy for esophageal squamous cell carcinoma: a phase 1/2 trial (PALACE-2). Signal Transduct Target Ther. 2025 Nov 28;10(1):386. doi: 10.1038/s41392-025-02477-4.
• Results Ghalehtaki R, Amini A, Abyaneh R. Optimizing neoadjuvant radiotherapy for locally advanced esophageal squamous cell carcinoma: a comprehensive review on the role of concomitant or sequential immune checkpoint inhibitors. Esophagus. 2025 Jan;22(1):5-18. doi: 10.1007/s10388-024-01097-1. Epub 2024 Nov 19.
• Results He W, Bai H, Lv J, Tang P, Hu T, Zhou H, Xiao W, Peng L, Liu G, Wang K, Fang Q, Qi Y, Liang L, Zheng X, Qing H, Chen Y, Zhou Y, Xie W, Han Y, Leng X. Neoadjuvant chemotherapy or chemoradiotherapy plus sintilimab versus neoadjuvant chemoradiotherapy for locally advanced oesophageal squamous cell carcinoma: a study protocol of a multicentre, randomised, controlled, phase III trial (SCIENCE study). BMJ Open. 2025 Jun 4;15(6):e095828. doi: 10.1136/bmjopen-2024-095828.

Drugs

Indications