Tislelizumab plus chemoradiotherapy (CRT) versus CRT or chemotherapy (CT) as the neoadjuvant treatment for patients (pts) with locally advanced gastric/gastroesophageal junction adenocarcinoma (GC/GEJC): A multicenter, randomized controlled, open-label, phase IIb study (TERRIFIC).

286 Background: MATTERHORN study has demonstrated that immunotherapy (IO) plus triple CT as neoadjuvant treatment significantly improves pCR and prolongs EFS in GC/GEJC. In the previous single-arm SHARED study, we found that IO plus CRT showed promising efficacy and manageable safety as perioperative treatment for GC/GEJC. This study aims to evaluate the efficacy and safety of tislelizumab (TIS) plus CRT, as compared to CRT or CT alone, in the neoadjuvant treatment of pts with GC/GEJC. Methods: Pts with histologically confirmed locally advanced GC/GEJC, stage III-IVa and no prior anticancer therapy were enrolled and randomized (2:2:1) to receive TIS (200 mg) plus CRT (45Gy, SOX or S1+nab-PTX) (arm A), CRT (arm B), or CT alone (SOX or S1+nab-PTX) (arm C) for 3 cycles as neoadjuvant treatment. After surgery, all pts would receive 3 cycles of CT followed by 3 cycles of S-1 as maintenance therapy, with arm A continuing TIS maintenance therapy for 12 months. The primary endpoint was pCR rate assessed in intent to treatment (ITT) set. Secondary endpoints included pCR rate assessed in pts underwent surgery, major pathological response (MPR) assessed in ITT and pts underwent surgery, 2-year EFS/OS rate and safety. Results: Herein, we reported the preliminary results. 87 pts were randomized (arm A, 35; arm B, 33; arm C, 19) with 58.6% T4a/b and 85.1% N2-3. Baseline characteristics were balanced between groups. 60 pts underwent surgery (arm A, 23; arm B, 24; arm C, 13). Efficacy was assessed in pts underwent surgery. The pCR rate was better in arm A versus arm C (34.8% vs. 0%) and arm A versus arm B (34.8% vs. 25%). The MPR rate was higher in arm A versus C (65.2% vs. 15.4%) and was similar between arm A and arm B (65.2% vs. 62.5%). Grade ≥3 TRAE occurred in 14.3% of arm A, 9.1% of arm B and 10.5% of arm C. Any grade irAE was reported in 9 (25.0%) pts of arm A. Conclusions: The preliminary results showed that TIS plus CRT had higher pCR rate over CRT or CT alone for pts with locally advanced GC/GEJC, further confirm the improved efficacy of IO as neoadjuvant therapy for GC/GEJC. Clinical trial information: NCT05687357 .