e16120 Background: Sintilimab is a PD-1 inhibitor that is approved for the treatment of advanced esophageal squamous cell carcinoma, but its efficacy and safety in locally advanced disease is unclear. We administered sintilimab with definitive chemoradiotherapy to patients with unresectable locally advanced oesophageal squamous cell carcinoma, and aimed to investigate the efficacy and safety of this treatment pattern. Methods: We conducted a multicenter, phase 2 trial at three cancer centers in sichuan province. Patients aged 18-75 years with untreated, unresectable, stage II-IVA esophageal squamous cell carcinoma, with an ECOG performance status of 0-2, and adequate organ and bone marrow function were eligible for inclusion. Patients received concurrent thoracic radiotherapy (60·0 Gy in 30 fractions), chemotherapy (two cycles of intravenous Albumin-Bound Paclitaxel [180 mg/m2, day1] and cisplatin [25 mg/m2, day1-3]), and Sintilimab (200 mg intravenously every 3 weeks for up to 1 year, or until disease progression or unacceptable toxicity). The primary endpoint was the progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate, quality of life (not reported here), and safety. The trial is registered with ClinicalTrials.gov, NCT046 02013. Enrolment is completed and follow-up is ongoing. Results: Between Oct 19, 2020, and Dec 08, 2023, 52 patients were enrolled. The median age was 65 years (IQR 58-71), 11 (21.1%) of 52 patients had stage IVA disease, and 49 (94.2%) patients were male and 3 (5.8%) were female. 50 (96.2%) of 52 patients patients completed the planned chemoradiotherapy. After a median follow-up of 15.0 months (IQR 7·9-28·0), the median PFS was not reached. The 1-, 2- and 3-year OS rates were 93.7%, 84.0% and 45.0%, respectively.The most common grade 3 or worse adverse event was neutropenia (23 [44.2%] of 52). Eight (15.4%) had treatment-related pneumonitis, but no patient died. Conclusions: Combining toripalimab with definitive chemoradiotherapy provided encouraging activity and acceptable toxicity in patients with locally advanced oesophageal squamous cell carcinoma, and this regimen warrants further investigation. Clinical trial information: NCT04602013 .