{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T01:16:38Z","timestamp":1789434998212,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,7,6]],"date-time":"2025-07-06T00:00:00Z","timestamp":1751760000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013170","name":"Ono Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013170","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    ONO\u20104578, 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\u20104578 plus nivolumab in unresectable advanced or recurrent gastric or gastroesophageal junction (G\/GEJ) cancer. Patients were enrolled into three groups: with previous immuno\u2010oncology treatment (IO\u2010treated;\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200930), without IO treatment (IO\u2010naive;\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200930), and with\n                    <jats:italic>UGT1A1<\/jats:italic>\n                    polymorphism (UGT1A1p;\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20096). Treatment\u2010related adverse events (TRAEs) occurred in 46 patients (grade 3\u20134 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\u2010treated and 16.7% and 40.0%, respectively, in IO\u2010naive. Biomarker analysis indicated immune activation in the tumor microenvironment after the treatment. In conclusion, ONO\u20104578 plus nivolumab showed a manageable safety profile and antitumor activity in G\/GEJ cancer.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    Japan Registry of Clinical Trials number: jRCT2080223441;\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                    identifier: NCT03155061\n                  <\/jats:p>","DOI":"10.1111\/cas.70130","type":"journal-article","created":{"date-parts":[[2025,7,6]],"date-time":"2025-07-06T18:10:09Z","timestamp":1751825409000},"page":"2523-2536","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["<scp>ONO<\/scp>\n                    \u20104578 Plus Nivolumab in Unresectable Advanced or Recurrent Gastric or Gastroesophageal Junction Cancer"],"prefix":"10.1111","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8632-3748","authenticated-orcid":false,"given":"Akihito","family":"Kawazoe","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Gastrointestinal Oncology National Cancer Center Hospital East  Kashiwa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensei","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department Director of Gastroenterological Chemotherapy Cancer Institute Hospital of Japanese Foundation for Cancer Research  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Hamaguchi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Oncology Saitama Medical University International Medical Center  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiya","family":"Narita","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology Aichi Cancer Center Hospital  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5015-0379","authenticated-orcid":false,"given":"Shogen","family":"Boku","sequence":"additional","affiliation":[{"name":"Cancer Treatment Center Kansai Medical University Hospital  Hirakata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Oshima","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery Kanagawa Cancer Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Saitama Cancer Center  Kitaadachi\u2010gun Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5737-122X","authenticated-orcid":false,"given":"Yasuo","family":"Hamamoto","sequence":"additional","affiliation":[{"name":"Keio Cancer Center Keio University School of Medicine  Shinjuku\u2010ku Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Ishido","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Kitasato University School of Medicine  Sagamihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9169-8453","authenticated-orcid":false,"given":"Taito","family":"Esaki","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Medical Oncology NHO Kyushu Cancer Center  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisashi","family":"Hosaka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Gunma Prefectural Cancer Center  Ota\u2010shi Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Yasui","sequence":"additional","affiliation":[{"name":"Division of Gastrointestinal Oncology Shizuoka Cancer Center  Shizuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Koeda","sequence":"additional","affiliation":[{"name":"Department of Medical Safety Science Iwate Medical University School of Medicine  Shiwa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Nishina","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology NHO Shikoku Cancer Center  Matsuyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Tsuji","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Tonan Hospital  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeo","family":"Fukagawa","sequence":"additional","affiliation":[{"name":"Department of Surgery School of Medicine Teikyo University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Goto","sequence":"additional","affiliation":[{"name":"Cancer Chemotherapy Center Osaka Medical and Pharmaceutical University Hospital  Takatsuki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9763-9366","authenticated-orcid":false,"given":"Eiji","family":"Oki","sequence":"additional","affiliation":[{"name":"Department of Surgery and Science, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naotoshi","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Department of Genetic Oncology Osaka International Cancer Institute  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Matsuoka","sequence":"additional","affiliation":[{"name":"Department of Surgery Fujita Health University  Toyoake Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiharu","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"Translational Research Group Ono Pharmaceutical Co., Ltd.  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Bioinformatics Group, Drug Discovery Tech Ono Pharmaceutical Co., Ltd.  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Statistical Analysis Section Ono Pharmaceutical Co., Ltd.  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Oshima","sequence":"additional","affiliation":[{"name":"Oncology Early Clinical Development Planning Ono Pharmaceutical Co., Ltd.  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Iwasa","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology National Cancer Center Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1412082"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504627"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1507643"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1510665"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)00587-0"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31827-5"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30626-6"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-015-0260-7"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/2047-1440-1-15"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2006.02376.x"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-20-1815"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15574"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.09.002"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v19.i42.7361"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0053-3"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.05.060"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612824666180629111227"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.7861\/clinmed.2021-0039"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30739-3"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2004413"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70420-6"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10120-021-01173-w"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.iotech.2022.100273"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-24-2611"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2024.42.3_suppl.93"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.05.066"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI97953"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(02)02302-5"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11788-4"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-022-00620-6"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-0436"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-1466"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.11.024"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-021-09998-8"},{"issue":"1","key":"e_1_2_11_37_1","first-page":"1","article-title":"Inhibition of PGE2\/EP4 Receptor Signaling Enhances Oxaliplatin Efficacy in Resistant Colon Cancer Cells Through Modulation of Oxidative Stress","volume":"9","author":"Huang H.","year":"2019","journal-title":"Scientific Reports"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.70130","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T10:30:48Z","timestamp":1756722648000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.70130"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,6]]},"references-count":36,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1111\/cas.70130"],"URL":"https:\/\/doi.org\/10.1111\/cas.70130","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,6]]},"assertion":[{"value":"2025-02-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}