Neoadjuvant tislelizumab combined with chemoradiotherapy for resectable locally advanced esophageal squamous cell carcinoma (ESCC): Single arm phase II study

4068 Background: This study aimed to evaluate the safety and efficacy of neoadjuvant tislelizumab combined with chemoradiotherapy in patients with resectable esophageal squamous cell cancer. Methods: This is a prospective single-arm clinical trial. A total of 20 patients with newly diagnosed resectable esophageal cancer (cT1-2N+ / cT3-4aN0-3 M0) received 2 cycles of tislelizumab (200mg every 3 weeks for 2 cycles) concurrent with chemoradiotherapy (radiotherapy: 41.4Gy in 23 fractions; chemotherapy: Paclitaxel (Albumin bound) 100mg/m 2 , and Cisplatin 75 mg/m 2 once every 3 weeks for 2 cycles.) Radical esophagectomy was performed within 4-6 weeks after neoadjuvant therapy. PET/CT was performed at baseline and before surgery. Primary endpoints included pathological response rate (pCR) and major pathological response rate (MPR), the secondary endpoints were disease free survival and safety. Exploratory endpoints include molecular imaging research and immune biomarker to further explore the factors affecting the efficacy of neoadjuvant therapy for esophageal cancer. Results: Twenty patients enrolled, all of whom received neoadjuvant tislelizumab combined with chemoradiotherapy. Eighteen patients underwent radical esophagectomy. One patient underwent radical chemoradiotherapy due to lymph node metastases after neoadjuvant therapy. One patient died of pneumonia before surgery. Among 18 patients who underwent surgery, R0 was 100% (18/18), 9 patients achieved pCR (50.0%), and 13 patients achieved MPR (72.2%). Most of treatment-related adverse event (TRAE) were grade 1-2, and the most common TRAE was anemia (15, 75.0%). The grade 3 TRAE included 1 leukopenia (5.0%), 1 neutropenia (5.0%), 1 liver damage (5.0%), and 1 elevated cardiac troponin T (5.0%). A significant decrease in SUVmax was observed in both pCR and no-pCR patients after treatment. Baseline SUVmax in no-pCR patients tended to be higher than pCR patients(p=0.0642). Furthermore, a significant increase in circulating CD4 + T cells, CD4 + effector memory T cells (T EM ), and M1 were found after treatment. Among the patients with pCR, the CD4 + T EM and cDCs after treatment were higher than those in the no-pCR patients, while Tregs and M2 were lower. Conclusions: Neoadjuvant tislelizumab combined with chemoradiotherapy for locally advanced ESCC has promising efficacy and good safety. Clinical trial information: NCT05323890 . [Table: see text]