A phase II trial of neoadjuvant chemotherapy combined with anti-angiogenesis therapy and immunotherapy for resectable stageII-IIIB esophageal squamous cell carcinoma.

e16124 Background: It has been proven that neoadjuvant therapy plays a vital part in the therapy of resectable esophageal squamous cell carcinoma (ESCC). Several studies have shown that adding immunotherapy to neoadjuvant chemo (-radiation) therapy can effectively improve R0 resection rate and even the prognosis. Toripalimab has been widely used in clinical practice of advanced staged carcinoma. Anti-angiogenesis therapy also plays an important role in treating advanced ESCC. Moreover, there have been a few of clinical studies attempting to add anti-angiogenesis therapy to neoadjuvant chemotherapy for ESCC, but no results reported so far. This study aims to explore the safety and efficacy of neoadjuvant chemotherapy combined with anti-angiogenesis therapy and immunotherapy for ESCC patients. Methods: This prospective, single-center, single-arm, phase 2 clinical trial recruits the treatment-naive patients with resectable ESCC. Twenty-five patients are planned to be enrolled in this study. Eligible patients are those with stage II to IIIB ESCC from cT2N1-2M0 to cT3N0-2M0, which have been pathologically diagnosed. They will receive Toripalimab 240mg plus Anlotinib 12mg (q.o.d. for two weeks) and chemotherapy (albumin-bound paclitaxel 200-260mg/m2 and Carboplatin 200-400mg/m2) every three weeks for four cycles. After the neoadjuvant therapy of 4-6weeks, patients will receive radical surgery for esophageal carcinoma. After surgery, Toripalimab will be administered for a year depending on patients’ will. The primary endpoint is the rate of pCR, and the secondary endpoints include ORR, DCR, DFS and OS. Results: In the first stage of the study, 4 patients achieved a pCR, allowing the trial to progress to the second phase. On the basis of Simon's Two-Stage design, 10 patients with stage II to IIIB ESCC from cT2N1-2M0 to cT3N0-2M0 were recruited for the first stage from the Nanfang Hospital, Southern Medical University from November 1, 2023, to June 25, 2024. The efficacy and safety analysis were evaluated in all patients (n = 10), 4 of the 10 patients achieved pCR (40%,) and 2 achieved mPR (20%). Evaluating by RECIST1.1 standard, the ORR was 90% (9/10, 95% CI, 59.59-98.21) and DCR was 100% (10/10, 95% CI, 72.25-100), while 5(50%) patients and 4 (40%) patients achieved a CR and PR respectively, and 1 (10%) patient got SD. The individual pathological results were not completely consistent with the imaging evaluation results. Among 10 patients in the first stage, 8 (80%) patients had treatment-related adverse events (TRAEs). More than 10% of incidence rate included paresthesia (n = 5), oral hemorrhage (n = 2), leukopenia (n = 2). G3-4 of TRAEs were dysphagia (n = 2). Conclusions: This neoadjuvant chemotherapy combined with anti-angiogenesis therapy and immunotherapy has exhibited notable efficacy and manageable safety profile in resectable ESCC. Clinical trial information: NCT05996484 .