Tislelizumab combined with chemotherapy or radiotherapy as neoadjuvant therapy for resectable esophageal squamous cell carcinoma (TINES): A randomized, open, phase II study.

e16090 Background: Although immunotherapy combined with chemotherapy has gradually been confirmed to improve the resectable esophageal squamous cell carcinoma (ESCC), it is necessary to explore other safe and efficient combination regimens. Radiotherapy could induce immunosensitization to improve the efficacy of PD-1 blocker, this study evaluated the efficacy and safety of tislelizumab combined with radiotherapy in resectable ESCC. Methods: 32 treatment-naïve patients with resectable ESCC (T 2-4a N any M 0 ) were planed and randomized (1:1) to two arms for neoadjuvant therapy. Arm A received tislelizumab (200 mg on day 1), paclitaxel (150 mg/m 2 on day 1) and cisplatin (75 mg/m 2 on day 1) once every 3 weeks for 3 cycles, and arm B received radiotherapy with 41.4 Gy in 23 fractions combined with 3 cycles (200 mg, Q3W) of tislelizumab. Surgery was planned in 4-6 weeks post neoadjuvant therapy. Postoperative adjuvant tislelizumab was given to arms A and B for up to 14 cycles. The primary endpoint was pathological complete response (pCR) rate. The secondary endpoints included major pathological response (MPR) rate, disease-free survival, overall survival and safety. Results: Between October 2022 to January 2024, 22 patients were enrolled: arm A (n = 12) and arm B (n = 10). 15 patients were male and 7 patients were female. The median age was 65 years (range, 37 to 75 years). 8 patients were in stage II, 13 were in stage III and 1 was in stage IV. 18 (81.8%) patients from arms A and B completed neoadjuvant therapy, and 10 patients underwent surgery, 6 patients were awaiting preoperative evaluation, still 2 surgery cancelations due to patient withdrawal for symptom improvement. The pCR rate was higher in arm B (25.0%, 1/4) compared to arm A (16.7%, 1/6). MPR rates were 83.3% and 75.0% for arms A and B. During neoadjuvant treatment, no grade 3-5 treatment-related adverse events were observed. Conclusions: Tislelizumab plus chemotherapy or radiotherapy as neoadjuvant therapy demonstrated encouraging therapeutic effect for resectable ESCC.