OSAKA, Japan, June 2, 2026
Ono Pharmaceutical announced positive Phase 2 clinical trial results for ONO-4578, its investigational oral EP4 antagonist, in patients with previously untreated HER2-negative unresectable advanced or recurrent gastric cancer and gastroesophageal junction cancer. Presented at the ASCO 2026 Annual Meeting, the study demonstrated that ONO-4578 combined with OPDIVO (nivolumab) and chemotherapy significantly improved progression-free survival (PFS) compared with placebo plus OPDIVO and chemotherapy. The findings support the continued development of ONO-4578 as a potential new immunotherapy-based treatment option for advanced gastric cancer.
Phase 2 Trial Meets Primary Endpoint with Significant PFS Improvement
Ono’s randomized Phase 2 ONO-4578-08 study successfully met its primary endpoint, showing a statistically significant improvement in progression-free survival. Patients receiving ONO-4578 in combination with OPDIVO and chemotherapy achieved a median PFS of 9.0 months, compared with 6.9 months in the placebo combination group. The treatment regimen also demonstrated encouraging improvements in secondary efficacy measures. Median overall survival (OS) was not reached in the ONO-4578 arm, compared with 12.7 months in the control group, while the objective response rate (ORR) improved to 62.0% versus 48.7% with standard treatment.
Stronger Clinical Benefit Observed in PD-L1 Positive Patients
The greatest benefit was observed among patients with PD-L1 Combined Positive Score (CPS) ≥1, a subgroup commonly associated with improved response to immunotherapy. In these patients, median PFS increased to 9.9 months with ONO-4578 compared with 5.7 months in the placebo group. Median overall survival remained unreached in the ONO-4578 arm versus 12.7 months for control patients, while objective response rates improved to 70.9% compared with 50.9%, respectively. These results suggest that ONO-4578 may significantly enhance the effectiveness of anti-PD-1 therapy and chemotherapy in biomarker-selected gastric cancer patients.
Advertisement
Phase 3 Development Planned Following Positive Results
ONO-4578 continued to demonstrate a manageable safety profile with no new safety signals identified during the study. The investigational therapy is designed to block the EP4 receptor, preventing prostaglandin E2-mediated immune suppression and potentially restoring anti-tumor immune responses. Based on the positive efficacy and safety data, Ono Pharmaceutical and its affiliate Deciphera plan to initiate a pivotal Phase 3 clinical trial to further evaluate ONO-4578 as a first-line treatment option for advanced HER2-negative gastric cancer. If future studies confirm these findings, the therapy could represent an important advancement for patients facing a disease with significant unmet medical needs.
Source: Ono Pharmaceutical press release
