ONO-4578 Plus Nivolumab in Unresectable Advanced or Recurrent Gastric or Gastroesophageal Junction Cancer

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

ONO-4578 Plus Nivolumab in Unresectable Advanced or Recurrent Gastric or Gastroesophageal Junction Cancer

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

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	2523-2536
Number of pages	14
Journal	Cancer science
Volume	116
Issue number	9
DOIs	https://doi.org/10.1111/cas.70130
Publication status	Published - 09-2025
Externally published	Yes

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/cas.70130

Cite this

Kawazoe, A., Yamaguchi, K., Hamaguchi, T., Narita, Y., Boku, S., Oshima, T., Hara, H., Hamamoto, Y., Ishido, K., Esaki, T., Hosaka, H., Yasui, H., Koeda, K., Nishina, T., Tsuji, Y., Fukagawa, T., Goto, M., Oki, E., Sugimoto, N., ... Iwasa, S. (2025). ONO-4578 Plus Nivolumab in Unresectable Advanced or Recurrent Gastric or Gastroesophageal Junction Cancer. Cancer science, 116(9), 2523-2536. https://doi.org/10.1111/cas.70130

@article{c4ffe8a0de004a6cba2864738630a4df,

title = "ONO-4578 Plus Nivolumab in Unresectable Advanced or Recurrent Gastric or Gastroesophageal Junction Cancer",

abstract = "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.",

keywords = "dose-limiting toxicity, gastric cancer, nivolumab, phase I, prostaglandin E2 receptor EP4",

author = "Akihito Kawazoe and Kensei Yamaguchi and Tetsuya Hamaguchi and Yukiya Narita and Shogen Boku and Takashi Oshima and Hiroki Hara and Yasuo Hamamoto and Kenji Ishido and Taito Esaki and Hisashi Hosaka and Hirofumi Yasui and Keisuke Koeda and Tomohiro Nishina and Yasushi Tsuji and Takeo Fukagawa and Masahiro Goto and Eiji Oki and Naotoshi Sugimoto and Hiroshi Matsuoka and Fumiharu Yokoyama and Tomoko Yoshida and Kazuo Yoshida and Yoshiaki Oshima and Satoru Iwasa",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s). Cancer Science published by John Wiley \& Sons Australia, Ltd on behalf of Japanese Cancer Association.",

year = "2025",

month = sep,

doi = "10.1111/cas.70130",

language = "English",

volume = "116",

pages = "2523--2536",

journal = "Cancer science",

issn = "1347-9032",

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Kawazoe, A, Yamaguchi, K, Hamaguchi, T, Narita, Y, Boku, S, Oshima, T, Hara, H, Hamamoto, Y, Ishido, K, Esaki, T, Hosaka, H, Yasui, H, Koeda, K, Nishina, T, Tsuji, Y, Fukagawa, T, Goto, M, Oki, E, Sugimoto, N, Matsuoka, H, Yokoyama, F, Yoshida, T, Yoshida, K, Oshima, Y & Iwasa, S 2025, 'ONO-4578 Plus Nivolumab in Unresectable Advanced or Recurrent Gastric or Gastroesophageal Junction Cancer', Cancer science, vol. 116, no. 9, pp. 2523-2536. https://doi.org/10.1111/cas.70130

TY - JOUR

T1 - ONO-4578 Plus Nivolumab in Unresectable Advanced or Recurrent Gastric or Gastroesophageal Junction Cancer

AU - Kawazoe, Akihito

AU - Yamaguchi, Kensei

AU - Hamaguchi, Tetsuya

AU - Narita, Yukiya

AU - Boku, Shogen

AU - Oshima, Takashi

AU - Hara, Hiroki

AU - Hamamoto, Yasuo

AU - Ishido, Kenji

AU - Esaki, Taito

AU - Hosaka, Hisashi

AU - Yasui, Hirofumi

AU - Koeda, Keisuke

AU - Nishina, Tomohiro

AU - Tsuji, Yasushi

AU - Fukagawa, Takeo

AU - Goto, Masahiro

AU - Oki, Eiji

AU - Sugimoto, Naotoshi

AU - Matsuoka, Hiroshi

AU - Yokoyama, Fumiharu

AU - Yoshida, Tomoko

AU - Yoshida, Kazuo

AU - Oshima, Yoshiaki

AU - Iwasa, Satoru

PY - 2025/9

Y1 - 2025/9

N2 - 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.

AB - 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.

KW - dose-limiting toxicity

KW - gastric cancer

KW - nivolumab

KW - phase I

KW - prostaglandin E2 receptor EP4

UR - https://www.scopus.com/pages/publications/105009849435

UR - https://www.scopus.com/pages/publications/105009849435#tab=citedBy

U2 - 10.1111/cas.70130

DO - 10.1111/cas.70130

M3 - Article

C2 - 40618725

AN - SCOPUS:105009849435

SN - 1347-9032

VL - 116

SP - 2523

EP - 2536

JO - Cancer science

JF - Cancer science

IS - 9

ER -

ONO-4578 Plus Nivolumab in Unresectable Advanced or Recurrent Gastric or Gastroesophageal Junction Cancer

Abstract

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UN SDGs

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