{"title":"ONO-4578联合尼武单抗治疗晚期或复发性胃癌或胃食管结癌","authors":"Akihito Kawazoe, Kensei Yamaguchi, Tetsuya Hamaguchi, Yukiya Narita, Shogen Boku, Takashi Oshima, Hiroki Hara, Yasuo Hamamoto, Kenji Ishido, Taito Esaki, Hisashi Hosaka, Hirofumi Yasui, Keisuke Koeda, Tomohiro Nishina, Yasushi Tsuji, Takeo Fukagawa, Masahiro Goto, Eiji Oki, Naotoshi Sugimoto, Hiroshi Matsuoka, Fumiharu Yokoyama, Tomoko Yoshida, Kazuo Yoshida, Yoshiaki Oshima, Satoru Iwasa","doi":"10.1111/cas.70130","DOIUrl":null,"url":null,"abstract":"<p>ONO-4578, an EP4 antagonist, alone and combined with nivolumab, showed acceptable safety profiles and signs of antitumor activity in solid tumors. The expansion part examined the safety, preliminary efficacy, and biomarkers of ONO-4578 plus nivolumab in unresectable advanced or recurrent gastric or gastroesophageal junction (G/GEJ) cancer. Patients were enrolled into three groups: with previous immuno-oncology treatment (IO-treated; <i>n</i> = 30), without IO treatment (IO-naive; <i>n</i> = 30), and with <i>UGT1A1</i> polymorphism (UGT1A1p; <i>n</i> = 6). Treatment-related adverse events (TRAEs) occurred in 46 patients (grade 3–4 in 17), with no grade 5 events reported. We confirmed the tolerability of the treatment in UGT1A1p. Objective response and disease control rates were 10.0% and 73.3%, respectively, in IO-treated and 16.7% and 40.0%, respectively, in IO-naive. Biomarker analysis indicated immune activation in the tumor microenvironment after the treatment. In conclusion, ONO-4578 plus nivolumab showed a manageable safety profile and antitumor activity in G/GEJ cancer.</p><p><b>Trial Registration:</b> Japan Registry of Clinical Trials number: jRCT2080223441; ClinicalTrials.gov identifier: NCT03155061</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 9","pages":"2523-2536"},"PeriodicalIF":4.3000,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70130","citationCount":"0","resultStr":"{\"title\":\"ONO-4578 Plus Nivolumab in Unresectable Advanced or Recurrent Gastric or Gastroesophageal Junction Cancer\",\"authors\":\"Akihito Kawazoe, Kensei Yamaguchi, Tetsuya Hamaguchi, Yukiya Narita, Shogen Boku, Takashi Oshima, Hiroki Hara, Yasuo Hamamoto, Kenji Ishido, Taito Esaki, Hisashi Hosaka, Hirofumi Yasui, Keisuke Koeda, Tomohiro Nishina, Yasushi Tsuji, Takeo Fukagawa, Masahiro Goto, Eiji Oki, Naotoshi Sugimoto, Hiroshi Matsuoka, Fumiharu Yokoyama, Tomoko Yoshida, Kazuo Yoshida, Yoshiaki Oshima, Satoru Iwasa\",\"doi\":\"10.1111/cas.70130\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>ONO-4578, an EP4 antagonist, alone and combined with nivolumab, showed acceptable safety profiles and signs of antitumor activity in solid tumors. The expansion part examined the safety, preliminary efficacy, and biomarkers of ONO-4578 plus nivolumab in unresectable advanced or recurrent gastric or gastroesophageal junction (G/GEJ) cancer. Patients were enrolled into three groups: with previous immuno-oncology treatment (IO-treated; <i>n</i> = 30), without IO treatment (IO-naive; <i>n</i> = 30), and with <i>UGT1A1</i> polymorphism (UGT1A1p; <i>n</i> = 6). Treatment-related adverse events (TRAEs) occurred in 46 patients (grade 3–4 in 17), with no grade 5 events reported. We confirmed the tolerability of the treatment in UGT1A1p. Objective response and disease control rates were 10.0% and 73.3%, respectively, in IO-treated and 16.7% and 40.0%, respectively, in IO-naive. Biomarker analysis indicated immune activation in the tumor microenvironment after the treatment. In conclusion, ONO-4578 plus nivolumab showed a manageable safety profile and antitumor activity in G/GEJ cancer.</p><p><b>Trial Registration:</b> Japan Registry of Clinical Trials number: jRCT2080223441; ClinicalTrials.gov identifier: NCT03155061</p>\",\"PeriodicalId\":9580,\"journal\":{\"name\":\"Cancer Science\",\"volume\":\"116 9\",\"pages\":\"2523-2536\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2025-07-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70130\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Science\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/cas.70130\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Science","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cas.70130","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
ONO-4578 Plus Nivolumab in Unresectable Advanced or Recurrent Gastric or Gastroesophageal Junction Cancer
ONO-4578, an EP4 antagonist, alone and combined with nivolumab, showed acceptable safety profiles and signs of antitumor activity in solid tumors. The expansion part examined the safety, preliminary efficacy, and biomarkers of ONO-4578 plus nivolumab in unresectable advanced or recurrent gastric or gastroesophageal junction (G/GEJ) cancer. Patients were enrolled into three groups: with previous immuno-oncology treatment (IO-treated; n = 30), without IO treatment (IO-naive; n = 30), and with UGT1A1 polymorphism (UGT1A1p; n = 6). Treatment-related adverse events (TRAEs) occurred in 46 patients (grade 3–4 in 17), with no grade 5 events reported. We confirmed the tolerability of the treatment in UGT1A1p. Objective response and disease control rates were 10.0% and 73.3%, respectively, in IO-treated and 16.7% and 40.0%, respectively, in IO-naive. Biomarker analysis indicated immune activation in the tumor microenvironment after the treatment. In conclusion, ONO-4578 plus nivolumab showed a manageable safety profile and antitumor activity in G/GEJ cancer.
Trial Registration: Japan Registry of Clinical Trials number: jRCT2080223441; ClinicalTrials.gov identifier: NCT03155061
期刊介绍：
Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports.
Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.
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