Efficacy and safety of IBI110 in combination with sintilimab in first-line advanced HER2negative gastric cancer or gastroesophageal junction cancer: Updated results from a phase Ib study

2576 Background: Sintilimab plus oxaliplatin and capecitabine (XELOX) has become the standard of care in patients (pts) with untreated advanced, recurrent, or metastatic gastric or gastroesophageal junction adenocarcinoma (G/GEJ AC) in China. Dual inhibition of PD-1 and lymphocyte-activation gene 3 (LAG-3) may further improve anti-tumor effect. The preliminary safety and efficacy data of IBI110 plus sintilimab and XELOX in pts with first-line G/GEJ AC were previously presented (Chenyu Mao et al. ASCO 2022). Here, we presented updated safety and efficacy results of this study. Methods: This phase Ib study enrolled patients with previously untreated, unresectable, locally advanced or recurrent/metastatic HER2-negative GC/GEJ AC. Pts received IBI110 200mg IV Q3W and sintilimab 200mg IV Q3W plus XELOX (oxaliplatin 130 mg/m2 Q3W and capecitabine 1000mg mg/m2/time twice daily [BID]) until disease progression, unacceptable toxicity or death. The primary objectives were to evaluate the safety, tolerability, and efficacy of the combination therapy per RECIST v1.1. Results: As of data cutoff January 9 th 2023, 17 pts were assessed as evaluable (median age: 61 years; ECOG PS=1: 14 pts; all gastric cancer). All pts (17/17, 100%) experienced treatment-related adverse events (TRAEs) of any grade, and the most commonly TRAEs were neutrophil count decreased (64.7%), white blood cell count decreased (52.9%), platelet count decreased (52.9%). Grade ≥ 3 TRAEs occurred in 11 pts (64.7%), the most frequent grade ≥ 3 TRAEs were consistent with TRAEs of any grade. Investigator-assessed immune-mediated adverse events (irAEs) occurred in 10 pts (58.8%). Grade ≥ 3 irAEs occurred in 3 pts (17.6%), all led to discontinuation. No treatment-related death occurred. As data cutoff, among 17 efficacy-evaluable pts, the unconfirmed and confirmed objective response rate (ORR) were 88.2% (95% CI, 63.6-98.5) and 64.7% (95% CI, 38.3-85.8), respectively. The disease control rate (DCR) was 94.1% (95% CI, 71.3-99.9). With a median follow up of 13.1 months (95% CI, 7.1-NC), the median duration of response (DoR) and progression-free survival (PFS) were 11.6 months (95% CI, 2.5-14.4) and 12.9 months (95% CI, 3.8-15.8), respectively. The median overall survival (OS) was not reached, and the 12-months OS rate was 70.6% (95% CI, 43.1-86.6). Conclusions: IBI110 in combination with sintilimab and XELOX demonstrated manageable safety and encouraging efficacy results in patients with first-line gastric adenocarcinoma. This is the first positive trial to show clinical benefits of a LAG3 plus PD-1 inhibitor combined with chemotherapy for this population. Clinical trial information: NCT04085185 .