Background: Sintilimab plus XELOX has been proven to be efficacious in the first line treatment of gastric cancer. Dual inhibition of PD-1 and lymphocyte-activation gene 3 (LAG-3) may improve anti-tumor effect synergistically. IBI110 (anti-LAG-3 mAb) plus sintilimab (anti-PD-1 mAb) has shown preliminary antitumor activity in advance solid tumors. This phase Ib cohort study evaluated the safety and efficacy of IBI110 in combination with sintilimab and XELOX regimen for advanced HER2-negative gastric or gastroesophageal junction adenocarcinoma (G/GEJ AC) in first-line setting. Methods: This phase Ib study enrolled patients with previously untreated, unresectable, locally advanced or recurrent/metastatic HER2-negative GC/GEJAC. Patients received IBI110 200mg IV Q3W and sintilimab 200mg IV Q3W plus oxaliplatin and capecitabine (XELOX) until disease progression, unacceptable toxicity or death. The primary objective was to evaluate the safety and tolerability, and efficacy of the combination therapy. Results: As data cutoff January 20^th 2022, 18 patients were enrolled, 6 patients had locally advanced/recurrent tumors, and 12 had metastatic tumors. The median follow up time was 4 weeks (range, 0-20). The median exposure of combination therapy was 9.4 weeks (range, 3-24). Any grade TRAEs occurred in 16 pts (88.9%); most commonly white bloo4d cell count decreased (n = 6; 33.3%), neutrophil count decreased (n = 6; 33.3%), and aspartate aminotransferase increased (n = 6; 33.3%). Grade ≥ 3 TRAEs occurred in 5 pts (27.8%), including neutrophil count decreased (n = 2; 11.1%), platelet count decreased (n = 2; 11.1%) and hepatic function abnormal (n = 2; 11.1%), platelet count decreased (n = 2; 11.1%) and hepatic function abnormal (n = 2; 11.1%). Immune-mediated AEs occurred in 7 pts (38.9%); most commonly amylase increased (n = 2; 11.1%). One patient discontinued treatment because of the coronary artery disease. There were no treatment-related death. For 15 evaluable patients, the ORR and DCR were 60% (9 PR) and 100% (9 PR,6 SD), respectively. The median duration of response (DOR) and median progression free survival (PFS) were not reached. As data cutoff, 17 patients were still in treatment. Conclusions: In this phase Ib study, IBI110 in combination with sintilimab and chemotherapy was well tolerated in the first line treatment of G/GEJ AC and the clinical benefit need more follow up time to be elucidated. Clinical trial information: NCT04085185.