2026-06-03 国立がん研究センター
図1. 無増悪生存期間の生存曲線
＜関連情報＞
- https://www.ncc.go.jp/jp/information/researchtopics/2026/0603/index.html
- https://ascopubs.org/doi/10.1200/JCO-26-01072
HER2陰性切除不能進行性または再発性胃癌または胃食道接合部癌に対するEP4拮抗薬ONO-4578とニボルマブおよび化学療法の併用療法 EP4 Antagonist ONO-4578 Plus Nivolumab and Chemotherapy in HER2-Negative Unresectable Advanced or Recurrent Gastric or Gastroesophageal Junction Cancer
Izuma Nakayama, MD, Min-Hee Ryu, MD, PhD, Sung Hee Lim, MD, Jong Gwang Kim, MD, Takeshi Omori, MD, Sang Cheul Oh, MD, Jin Young Kim, MD, … , and Kohei Shitara, MD
Journal of Clinical Oncology Published:June 01, 2026
DOI:10.1200/JCO-26-01072
Abstract
Purpose
EP4, a key receptor in the PGE2 axis, mediates tumor immunosuppression; the EP4 antagonist ONO-4578 plus nivolumab showed manageable safety, immune activation, and preliminary antitumor activity in previously treated gastric/gastroesophageal junction cancer (G/GEJC). This study explored whether ONO-4578 enhances the efficacy of nivolumab plus chemotherapy in unresectable advanced or recurrent G/GEJC.
Patients and Methods
This multicenter, double-blind, randomized phase 2 study enrolled chemotherapy-naïve patients with HER2-negative unresectable advanced or recurrent G/GEJC. Patients were randomized (2:1) to receive oral ONO-4578 or matching placebo, each in combination with nivolumab and oxaliplatin-based chemotherapy. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), and safety.
Results
At the data cutoff, 226 patients were randomized to the ONO-4578 group (n = 150) and the placebo group (n = 76). Adding ONO-4578 significantly improved PFS (hazard ratio of 0.67; 90% confidence interval, 0.48–0.92; p-value, 0.040 [prespecified two-sided α = 0.10]), with favorable OS at a prespecified analysis with limited follow-up (hazard ratio of 0.60; 95% confidence interval, 0.37–0.96) and ORR (62.0% vs 48.7%). Exploratory subgroup analyses suggested that ONO-4578 regimen provided greater benefit in PD-L1 CPS ≥1, whereas no clear benefit in CPS <1/indeterminate patients. In an extended follow-up exploratory OS analysis with a minimum follow-up of 16.1 months, OS numerically favored ONO-4578 regimen. Common treatment-emergent adverse events in the ONO-4578 group were diarrhoea (55.7% vs 45.3%), and anaemia (55.0% vs 34.7%).
Conclusion
This study demonstrated promising efficacy and acceptable safety of an ONO-4578 regimen as first-line treatment for HER2-negative unresectable advanced or recurrent G/GEJC. These findings warrant confirmation in a phase 3 trial.
