Tislelizumab Combined With Induction Chemotherapy and Concurrent Chemoradiotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma: A Multicenter, Randomized, Phase II Trial (EC-CRT-002)

PURPOSE: To evaluate the efficacy and safety of adding tislelizumab to induction chemotherapy and concurrent chemoradiotherapy (CRT), with or without maintenance immunotherapy, in patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: This multicenter, randomized, open-label, phase II trial was conducted across four academic hospitals in China (ClinicalTrials.gov identifier: NCT05520619). Participants were adults age 18-70 years with newly diagnosed, unresectable, stage II to IVB ESCC. Patients were randomly assigned (1:1) to receive two cycles of paclitaxel/cisplatin induction chemotherapy followed by concurrent CRT in combination with tislelizumab for 16 cycles in group A (two induction, two concurrent, and 12 maintenance) or four cycles in group B (two induction and two concurrent). The primary end point was progression-free survival (PFS) in the intention-to-treat population, compared with historical control. RESULTS: T-cell density, NRF2 pathway mutations, and dynamic changes in circulating tumor DNA were associated with treatment efficacy. CONCLUSION: The addition of tislelizumab to induction chemotherapy and concurrent CRT without maintenance immunotherapy demonstrated superior efficacy and manageable toxicity in locally advanced ESCC.