1416P - First-line tislelizumab combined with bevacizumab and CAPOX for metastatic gastroesophageal adenocarcinoma (mGEA) with PD-L1 CPS<5: Updated results of a phase II, prospective, single-arm study

Background

The combination of PD-1 antibody plus chemotherapy was approved as standard first-line treatment for mGEA. However, outcomes remain poor in pts with low PD-L1 expression. This prospective phase 2 trial was designed to explore the efficacy and safety of tislelizumab plus bevacizumab and chemotherapy in mGEA with PD-L1 CPS<5. Preliminary data was reported (Ru Jia, 2023 IGCC). Here we presented the updated data as more pts were recruited.

Methods

mGEA pts with PD-L1 CPS<5 and HER2(-) received tislelizumab and bevacizumab, in combination with standard CAPOX regimen up to 8 cycles, followed by tislelizumab, bevacizumab and capecitabine until disease progression. The primary endpoint was 6-months PFS rate, and secondary endpoints included ORR, PFS, OS, DCR and safety profiles. We collected 7 tumor tissue samples at baseline and evaluated the immune cell infiltration and DEGs based on the RNA-seq data.

Results

From Aug, 2021 to Apr, 2024, 27 pts were enrolled. The median age was 59 years and the majority were poorly-differentiated (96.3%). Additionally, 40.7% of pts were PD-L1 CPS<1 (22C3). Of the 26 pts evaluable for efficacy, 1 achieved CR (3.8%), 14 achieved confirmed PR (53.8%), and 11 exhibited SD (42.3%). The ORR was 57.7% and DCR was 100%. Among 20 pts with measurable disease, the ORR was 75.0% (15/20). The mPFS was 8.6 months (95% CI: 6.8-10.4). The most frequent treatment-related adverse events (TRAEs) of any grades included nausea and vomiting (55.6%), myelosuppression (37.0%), anorexia (33.3%), liver damagaige (25.9%) and fatigue (22.2%). Eight patients (29.6%) developed grade 3-4 TRAEs, with no new safety signals observed. The majority of patients exhibited an immune 'cold' phenotype (6/7) and the significantly up-regulated genes were GSTP1 and pathways related to reactive oxygen species metabolic processes were enriched in PR pts.

Conclusions

Tislelizumab plus bevacizumab and CAPOX demonstrated promising efficacy in PD-L1 <5, HER2(-), locally advanced or metastatic GEA pts, with a manageable safety profile. This trial is ongoing and the regimen deserves further exploration.

Clinical trial identification

NCT05299476.

Editorial acknowledgement

Legal entity responsible for the study

G. Dai.

Funding

Department of Medicine, Kanghui Biotech Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.