Conversion surgery for tislelizumab combined chemotherapy for T4a/N3 esophageal squamous cell carcinoma (ESCC): A prospective, single-arm, phase II study.

4069 Background: T4a/N3 ESCC is treated with neoadjuvant concurrent chemoradiotherapy plus surgery or radical chemoradiotherapy according to NCCN guidelines. This study aimed to evaluate the safety and efficacy of conversion therapy of Tislelizumab combined with chemotherapy in patients with T4a/N3 ESCC. Methods: This is a prospective, single-arm, single-center clinical trial. A total of 40 patients with newly diagnosed ESCC (cT4a/N3) received 2-4 cycles of paclitaxel (135 mg/m 2 ) on day 1, and cisplatin (80 mg/m 2 ) on day 1, Tislelizumab (200 mg) on day 2, every 3 weeks. After an efficacy evaluation, the patients will undergo radical esophagectomy resection within 4-6 weeks after conversion therapy. The primary endpoints are the safety and the R0 resection rate. The secondary endpoints include the objective response rate (ORR), a postoperative pathological complete response (pCR), major pathological response (MPR), overall survival (OS), disease-free survival (DFS). Exploratory endpoint is to examine immune biomarker of the efficacy of conversion therapy for ESCC. Results: 40 patients were enrolled, the ORR was 95%(38/40), and 60% (24/40) patients who completed conversion treatment underwent esophagectomy. R0 resection rate was 100% (24/24) with no reoperations or perioperative deaths. 70% (28/40) patients experienced at least one treatment-related adverse event (TRAE) and 12.5% (5/40) patients reported grade 3 and above TRAEs. For these surgical patients, the MPR and pCR rates were 33% (8/24) and 20.8% (5/24) respectively. Flow cytometry showed that the percentage of CD3 + CD4 + CD8 - T cells was significantly increased in peripheral blood after conversion therapy (p-value 0.02). Conclusions: Tislelizumab combined with chemotherapy, followed by radical esophagectomy resection has promising efficacy and good safety for T4a/N3 ESCC. Clinical trial information: NCT05449483 .