ONO-4578

Ono Pharmaceutical’s selective prostaglandin E2 receptor 4 antagonist is aimed at targeting immunosuppressive factors in the tumor microenvironment. \n Ono Pharmaceutical’s EP4 antagonist hit the primary progression-free survival endpoint in a phase 2 trial in patients with gastric cancer.The biopharma evaluated the Bristol Myers Squibb-partnered candidate, dubbed ONO-4578, in combination with the PD-1 blocker Opdivo and chemotherapy in patients in Japan, South Korea and Taiwan with HER2-negative unresectable advanced or recurrent gastric cancer or gastroesophageal junction cancer.The study tied this combo treatment regimen to a statistically significant prolongation of progression-free survival when compared to placebo, hitting the trial’s primary endpoint.Ono didn’t share any data in the sparse press release, promising to unveil the findings at future academic meeting.The selective prostaglandin E2 receptor 4 antagonist is aimed at targeting immunosuppressive factors in the tumor microenvironment. Japan-based Ono reaffirmed today that it is conducting several other trials of ONO-4578, including a global phase 2 study in patients with colorectal cancer.Ono codeveloped Opdivo with BMS, and the Japanese biopharma scored its own FDA approval earlier this year for Romvimza to treat a type of noncancerous growth. BMS spotted ONO-4578’s potential back in 2017, when the U.S. pharma paid $40 million upfront for the rights to the drug outside of Japan, South Korea, Taiwan, China and Association of Southeast Asian Nations (ASEAN) countries.Under the terms of that deal, BMS and Ono have partnered on developing ONO-4578 in Japan, South Korea and Taiwan under the two companies’ longstanding collaboration agreement. In China and ASEAN countries, Ono retained the exclusive rights.“To improve long-term outcomes for more patients with cancer, we believe more immuno-oncology based combinations may be required, and we are pleased to continue our long-standing collaboration with Ono with this focus in mind,” BMS explained at the time. 

ONO-4578, an EP4 antagonist, in combination with Opdivo and chemotherapy demonstrated a significant prolongation of progression-free survival compared with placebo in combination with Opdivo and chemotherapy, meeting the primary endpoint The Phase 2 clinical trial was conducted in Japan, South Korea, and Taiwan in patients with previously untreated, HER2-negative unresectable advanced or recurrent gastric cancer (including gastroesophageal junction cancer) OSAKA, Japan--(BUSINESS WIRE)--Ono Pharmaceutical Co., Ltd. (Headquarters: Osaka, Japan; President and COO: Toichi Takino; ”Ono”) announced that ONO-4578, an EP4 antagonist, in combination with Opdivo, an anti–PD-1 antibody and chemotherapy which is one of the standard treatments in this setting met the primary endpoint in the Phase 2 clinical trial (ONO-4578-08 study) in patients with previously untreated, HER2-negative unresectable advanced or recurrent gastric cancer (including gastroesophageal junction cancer). In the trial, ONO-4578 in combination with Opdivo and chemotherapy demonstrated a statistically significant prolongation of progression-free survival (PFS) compared with placebo in combination with Opdivo and chemotherapy. In addition, no new safety concerns were identified in the trial. Ono will publish the results at an upcoming academic meeting. About ONO-4578-08 study ONO-4578-08 study is a multicenter, randomized Phase 2 clinical trial, conducted in Japan, South Korea and Taiwan in patients with previously untreated, HER2-negative unresectable advanced or recurrent gastric cancer or gastroesophageal junction cancer. ONO-4578 in combination with Opdivo and chemotherapy (S-1 + oxaliplatin or capecitabine + oxaliplatin) was compared with placebo in combination with Opdivo and chemotherapy. In this trial, patients received 40 mg of ONO-4578 once daily and 360 mg of Opdivo every 3 weeks in combination with chemotherapy until disease progression or unacceptable toxicity was observed. The primary endpoint of this trial is PFS. About Gastric cancer It is estimated that approximately 126,000 new cases with gastric cancer are diagnosed per year in Japan1) (approximately 968,000 cases worldwide2)) and approximately 43,000 deaths per year in Japan1) (approximately 660,000 deaths worldwide2)) resulting from gastric cancer, which is the third most common type of cancer following colorectal cancer and lung cancer in Japan. Combination therapies with anti–PD-1 antibody and chemotherapy have been approved for the first-line treatment of HER2-negative unresectable advanced or recurrent gastric cancer as the standard treatment. However, unresectable gastric cancer remains incurable, and a new treatment option is needed for patients with gastric cancer. About ONO-4578 ONO-4578 is a selective, oral antagonist of EP4, which is one of the prostaglandin E2 (PGE2) receptors, developed by Ono. PGE2, which is produced by cancer cells, suppresses the action of cancer immunity through EP4 receptors expressed on various immune cells3)~5). ONO-4578 is expected to exert antitumor effect by suppressing EP4-mediated effects of PGE2 and by restoring cancer immunity6). In the phase 1 clinical trial in patients with unresectable advanced or recurrent gastric cancer (including gastroesophageal junction cancer) after the third- or later-line treatment, a combination therapy with ONO-4578 and Opdivo showed antitumor effect and a manageable safety profile7). Currently, Ono is conducting several clinical trials of ONO-4578, including a global phase 2 clinical trial in patients with colorectal cancer. References: 1) Globocan 2022: Stomach Cancer, Japan, World Health Organization Available at: https://gco.iarc.who.int/media/globocan/factsheets/populations/392-japan-fact-sheet.pdf 2) Globocan 2022: Stomach Cancer, World, World Health Organization Available at: https://gco.iarc.who.int/media/globocan/factsheets/populations/900-world-fact-sheet.pdf 3) Obermajer N, et al. Transplant Res. 2012;1:15. 4) Ylöstalo JH, et al. Stem Cells. 2012;30:2283-96. 5) Okano M, et al. Immunology. 2006;118:343-52. 6) Kotani T, et al. Cancer Res. 2020;80:16_Supplement 4443. 7) Kawazoe A, et al. Cancer Sci. 2025;116:2523-36.