Ono Pharmaceutical's EP4 Antagonist Shows Promise in Phase 2 Gastric Cancer Trial

Ono Pharmaceutical has announced positive results from a phase 2 trial of its EP4 antagonist, ONO-4578, in combination with Bristol Myers Squibb's (BMS) Opdivo and chemotherapy for patients with HER2-negative unresectable advanced or recurrent gastric cancer or gastroesophageal junction cancer.

Trial Results and Significance

The study, conducted across Japan, South Korea, and Taiwan, met its primary endpoint, demonstrating a statistically significant prolongation of progression-free survival compared to placebo. This combination treatment regimen represents a potential new approach to targeting immunosuppressive factors in the tumor microenvironment.

While specific data points were not disclosed in the initial announcement, Ono has committed to presenting detailed findings at upcoming academic meetings. The positive outcome of this trial marks a significant step forward in the development of novel therapies for gastric cancer, a disease with historically limited treatment options.

Ongoing Development and Partnership

ONO-4578, a selective prostaglandin E2 receptor 4 antagonist, is currently being evaluated in several other clinical trials. Notably, a global phase 2 study in colorectal cancer patients is underway, highlighting the compound's potential across multiple oncology indications.

The development of ONO-4578 is part of a longstanding collaboration between Ono Pharmaceutical and Bristol Myers Squibb. In 2017, BMS recognized the potential of this compound, securing rights to the drug outside of Japan, South Korea, Taiwan, China, and ASEAN countries for an upfront payment of $40 million. The partnership agreement allows for joint development in specified Asian markets, while Ono retains exclusive rights in China and ASEAN countries.

Implications for Immuno-Oncology

This latest development underscores the growing importance of combination therapies in immuno-oncology. As noted by BMS at the time of the initial partnership, "To improve long-term outcomes for more patients with cancer, we believe more immuno-oncology based combinations may be required."

The success of ONO-4578 in this phase 2 trial not only validates the ongoing collaboration between Ono and BMS but also reinforces the potential of targeting the EP4 receptor as a strategy to enhance the efficacy of existing immunotherapies like Opdivo.