Neoadjuvant chemoradiotherapy (nCRT) combined with sequential tislelizumab for resectable esophageal squamous cell carcinoma (ESCC): Preliminary results of a single-arm, open-label phase Ib trial (CRIS).

e16116 Background: Neoajuvant chemoradiation is the standard treatment for resectable locally advanced esophageal squamous cell carcinoma (ESCC). Immune checkpoint inhibitors (ICIs) have shown a survival benefit for advanced ESCC and showed promising efficacy in neoadjuvant treatment for several cancers. This study aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) combined with sequential tislelizumab followed by surgery for resectable ESCC. Methods: This is a single-arm, phase Ib study. Eligibility criteria include histologically confirmed ESCC and clinical T3-4aN0M0 or T2-4aN+M0 (AJCC/UICC 8 th ). Patients received neoadjuvant radiotherapy (41.4Gy in 23 fractions) with concurrent chemotherapy (paclitaxel, 50 mg/m2, carboplatin area under the curve of 2mg/mL/min, QW*5). Then followed by two cycles of tislelizumab (200mg, Q3W). The primary endpoint was the pathological complete response (pCR) rate and safety. Results: From Feb 2022 to Jan 2024, 35 patients had been enrolled, of whom the median age was (65.5 (95%CI, 59-67), including 31 (88.6%) males. 12 patients were still undergoing chemoradiotherapy and 2 patients did not receive immunotherapy due to pneumonia and myocarditis after chemoradiotherapy. 16 patients completed all 2 cycles tislelizumab preoperatively and 5 patients completed 1 cycle tislelizumab because of AEs. Two patients refused surgery after achieved complete clinical response under radiology and were still alive, the other 19 patients underwent resection. The R0 resection rate was 94.7% (18/19). The pCR rate was 63.2% (12/19) and the MPR rate was 78.9% (15/19). During neoadjuvant treatment, 8 patients had a grade 3 or worse adverse event including leukopenia (33.3%, 7/21, Grade 3), esophagitis (4.8%, 1/21, Grade 3) and anemia (4.8%, 1/20, Grade 4). One patient developed grade 4 postoperative complication (5.3%, 1/19, pneumonia) and died within 90 days of surgery due to COVID-19. Grade 1-2 postoperative complications occurred in 21.1% (4/19) patients, including anastomotic fistula (21.1%, 4/19), chylothorax (5.3%, 1/19) and pneumonia (10.5%, 2/19). Conclusions: Preliminary results showed that neoadjuvant chemoradiotherapy (nCRT) combined with sequential tislelizumab showed promising outcomes and well tolerated for resectable ESCC patients. Further larger prospective studies are needed to confirm such findings.