1032P - A phase II study of sintilimab plus IBI310 for Epstein-Barr virus (EBV)-associated gastric cancer

Background

EBV is associated with about 10% of gastric cancers. Preliminary data has indicated that patients(pts) with EBV-associated gastric cancer (EBVaGC) could benefit from immunotherapy. The purpose of this study is to evaluate safety and efficacy of sintilimab (anti-PD-1) plus IBI310 (anti-CTLA-4) for EBVaGC. The preliminary results of first-line (cohort B) and ≥ 2 line (cohort C) settings were reported. The study is still recruiting.

Methods

Adult pts with EBV+ (in situ hybridization, ISH), unresectable locally advanced or metastatic, histopathologically confirmed GC/GEJC (cohort B: pts with treatment-naïve; cohort C, pts who had failed at least one standard treatment regimen) were enrolled. Pts in both cohorts received sintilimab 3mg/kg (200mg for weight≥60kg）IV Q3W plus IBI310 1mg/kg IV Q6W combination regimen for 1-3 cycles, and sintilimab monotherapy maintenance thereafter until disease progression, unacceptable toxicity or for up to 24 months. The endpoints include ORR per RECIST v1.1 by investigator, other efficacy measures and safety profile in both cohorts.

Results

As of Feb 22, 2023, 49 pts were enrolled (28 in cohort B and 21 in cohort C). Any and grade ≥ 3 treatment-related adverse events (TRAEs) occurred in 38 (77.6%) and 10 (20.4%) pts, respectively. No TRAE leading to drug discontinuation or death. Any and grade ≥ 3 immune related adverse events (irAEs) occurred in 33 (67.3%) and 7 (14.3%) pts, respectively. In cohort B, for 26 efficacy evaluable pts, the confirmed ORR were 61.5% (95% CI, 40.6-79.8), and DCR was 80.8% (95% CI, 60.7-93.5). The median DoR was 8.3 months (95% CI, 4.0-15.1). With a median follow-up of 13.3 months, the median PFS and OS were 5.5 months (95% CI, 2.8-9.7) and 24.6 months (95% CI, 10.3-28.8), respectively. In cohort C, for 17 efficacy evaluable pts, the confirmed ORR was 47.1% (95% CI: 23.0-72.2) and the DCR was 76.5% (95% CI, 50.1-93.2). The median DoR was 5.6 months (95% CI, 1.4-NR). With a median follow-up of 21.1 months, the median PFS and OS were 5.4 months (95% CI, 1.3-8.4) and 12.8 months (95% CI, 4.1-NR), respectively.

Conclusions

Sintilimab in combination with IBI310 were well tolerated, and shown promising anti-tumor efficacy both in first-line and ≥ 2 line locally advanced or metastatic EBV-associated gastric cancer.

Clinical trial identification

NCT04202601.

Editorial acknowledgement

Lin Shen is the corresponding author.

Legal entity responsible for the study

Innovent Biologics Inc.

Funding

Innovent Biologics Inc.

Disclosure

Y. Zhang, Y. Luo, L. Li, H. Zhou: Personal, Emplyment: Innovent Biologics, Inc.. All other authors have declared no conflicts of interest.