A Study to Investigate the Efficacy and Safety of ONO-4578 in Combination With Nivolumab and Chemotherapy in Chemotherapy-naïve Participants With HER2-negative Unresectable Advanced or Recurrent Gastric Cancer (Including Esophagogastric Junction Cancer)

March 11, 2026 updated by: Ono Pharmaceutical Co. Ltd

A Randomized, Multicenter, Double-blind, Phase II Study to Compare the Efficacy and Safety of the Treatment With ONO-4578 in Combination With Nivolumab, Fluoropyrimidine-based and Platinum- Based Chemotherapy (Hereinafter Referred to as Chemotherapy) With Those of the Treatment With Placebo in Combination With Nivolumab and Chemotherapy in Chemotherapy-naïve Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Unresectable Advanced or Recurrent Gastric Cancer (Including Esophagogastric Junction Cancer)

This study is to compare and evaluate the efficacy and safety of the treatment with ONO-4578 in combination with nivolumab and chemotherapy with those of the treatment with placebo in combination with nivolumab and chemotherapy in chemotherapy-naïve participants with HER2- negative unresectable advanced or recurrent gastric cancer (including esophagogastric junction cancer).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

226

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
    • Aichi-ken
      • Nagoya, Aichi-ken, Japan
        • Aichi Cancer Center Hospital
    • Chiba
      • Kashiwa-shi, Chiba, Japan
        • National Cancer Center Hospital East
    • Ehime
      • Matsuyama, Ehime, Japan
        • Matsuyama Red Cross Hospital
      • Matsuyama, Ehime, Japan
        • NHO Shikoku Cancer Center
    • Fukuoka
      • Fukuoka, Fukuoka, Japan
        • Kyushu University Hospital
      • Fukuoka, Fukuoka, Japan
        • NHO Kyushu Cancer Center
      • Yahatanishi-ku, Kitakyusyu-shi, Fukuoka, Japan
        • JCHO Kyushu Hospital
    • Gunma
      • Ota-shi, Gunma, Japan
        • Gunma Prefectural Cancer Center
    • Hiroshima
      • Hiroshima, Hiroshima, Japan
        • Hiroshima City Hiroshima Citizens Hospital
    • Hyōgo
      • Akashi-shi, Hyōgo, Japan
        • Hyogo Cancer Center
      • Amagasaki-shi, Hyōgo, Japan
        • JOHAS Kansai Rosai Hospital
      • Kobe, Hyōgo, Japan
        • Kobe City Hospital Organization Kobe City Medical Center General Hospital
    • Ibaraki
      • Kasama-shi, Ibaraki, Japan
        • Ibaraki Prefectural Central Hospital
    • Ishikawa-ken
      • Kanazawa, Ishikawa-ken, Japan
        • Ishikawa Prefectural Central Hospital
    • Iwate
      • Yahaba-cho, Shiwa-gun, Iwate, Japan
        • Iwate Medical University Hospital
    • Kagawa-ken
      • Miki-cho, Kita-gun, Kagawa-ken, Japan
        • Kagawa University Hospital
    • Kanagawa
      • Sagamihara-shi, Kanagawa, Japan
        • Kitasato University Hospital
      • Yokohama, Kanagawa, Japan
        • Kanagawa Cancer Center
    • Miyagi
      • Osaki-shi, Miyagi, Japan
        • Osaki Citizen Hospital
      • Sendai, Miyagi, Japan
        • Tohoku University Hospital
    • Okayama-ken
      • Kurashiki-shi, Okayama-ken, Japan
        • Kurashiki Central Hospital
    • Osaka
      • Chuo-ku, Osaka, Japan
        • Osaka International Cancer Institute
      • Hirakata-shi, Osaka, Japan
        • Kansai Medical University Hospital
      • Osaka, Osaka, Japan
        • Osaka Metropolitan University Hospital
      • Sayama-shi, Osaka, Japan
        • Kindai University Hospital
      • Sumiyoshi-ku, Osaka, Japan
        • Osaka General Medical Center
      • Takatsuki-shi, Osaka, Japan
        • Osaka Medical and Pharmaceutical University Hospital
    • Saitama
      • Ina-machi, Kitaadati-gun, Saitama, Japan
        • Saitama Cancer Center
    • Shizuoka
      • Nagaizumi-cho, Sunto-gun, Shizuoka, Japan
        • Shizuoka Cancer Center
    • Tokyo
      • Koto-ku, Tokyo, Japan
        • Cancer Institute Hospital of JFCR
      • Minato-Ku, Tokyo, Japan
        • IMSUT Hospital, The Institute of Medical Science, The University of Tokyo
      • Shinjuku-ku, Tokyo, Japan
        • Keio University Hospital
  • South Korea
      • Busan, South Korea
        • Dong-A University Hospital
      • Daegu, South Korea
        • Kyungpook National University Chilgok Hospital
      • Daegu, South Korea
        • Keimyung University Dongsan Hospital
      • Daegu, South Korea
        • Yeungnam University Hospital
      • Incheon, South Korea
        • Gachon University Gil Medical Center
      • Incheon, South Korea
        • Inha University Hospital
      • Seoul, South Korea
        • Asan Medical Center
      • Seoul, South Korea
        • Kangbuk Samsung Hospital
      • Seoul, South Korea
        • Korea University Guro Hospital
      • Seoul, South Korea
        • Samsung Medical Center
      • Seoul, South Korea
        • Severance Hospital, Yonsei University Health System
      • Seoul, South Korea
        • The Catholic University of Korea, Eunpyeong St. Mary's Hospital
      • Seoul, South Korea
        • Kyung Hee University Hospital
      • Ulsan, South Korea
        • Ulsan University Hospital
    • Gangwon-do
      • Busan, Gangwon-do, South Korea
        • Kosin University Gospel Hospital
    • Gyeonggi-do
      • Anyang-si, Gyeonggi-do, South Korea
        • Hallym University Sacred Heart Hospital
      • Goyang-si, Gyeonggi-do, South Korea
        • National Cancer Center
      • Seongnam-si, Gyeonggi-do, South Korea
        • Seoul National University Bundang Hospital
      • Seongnam-si, Gyeonggi-do, South Korea
        • CHA Bundang Medical Center, CHA University
      • Suwon, Gyeonggi-do, South Korea
        • Ajou University Hospital
      • Suwon, Gyeonggi-do, South Korea
        • The Catholic University of Korea, St. Vincent's Hospital
    • Gyeongsangnam-do
      • Yangsan, Gyeongsangnam-do, South Korea
        • Pusan National University Yangsan Hospital
    • Jeollabuk-do
      • Jeonju, Jeollabuk-do, South Korea
        • Jeonbuk National University Hospital
    • Jeollanam-do
      • Hwasun-gun, Jeollanam-do, South Korea
        • Chonnam National University Hwasun Hospital
    • North Chungcheong
      • Cheongju-si, North Chungcheong, South Korea
        • Chungbuk National University Hospital
  • Taiwan
      • Kaohsiung City, Taiwan
        • Kaohsiung Medical University Chung-Ho Memorial Hospital
      • Taichung, Taiwan
        • China Medical University Hospital
      • Tainan, Taiwan
        • National Cheng Kung University Hospital
      • Tainan, Taiwan
        • Chi Mei Hospital, Liouying
      • Taipei, Taiwan
        • National Taiwan University Hospital
      • Taoyuan District, Taiwan
        • Chang Gung Memorial Hospital, Linkou

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with gastric or esophagogastric junction cancer histologically diagnosed as adenocarcinoma
  • Patients have not been treated with systemic chemotherapy as first-line therapy
  • Patients who can provide tumor tissue samples

Exclusion Criteria:

  • Patients unable to take oral medicines
  • Patients with HER2-positive
  • Patients with contraindications to nivolumab, oxaliplatin, S-1, or capecitabine
  • Patients who have a history of severe drug-related adverse reactions caused by non- steroidal anti-inflammatory drugs (NSAIDs) or who have complications caused by NSAIDs requiring treatment
  • Patients with concurrent autoimmune disease or a history of chronic or recurrent autoimmune disease, such as rheumatoid arthritis
  • Patients with headache and/or nausea associated with brain metastasis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ONO-4578+Nivolumab+chemotherapy
Drug: Nivolumab
Specified dose on specified days
Other Names:
  • Opdivo
Drug: Oxaliplatin
Specified dose on specified days
Drug: Capecitabine
Specified dose on specified days
Drug: S-1
Specified dose on specified days
Other Names:
  • Tegafur-gimeracil-oteracil potassium
Drug: ONO-4578
Specified dose, once daily
Placebo Comparator: placebo+Nivolumab+chemotherapy
Drug: Nivolumab
Specified dose on specified days
Other Names:
  • Opdivo
Drug: Oxaliplatin
Specified dose on specified days
Drug: Capecitabine
Specified dose on specified days
Drug: S-1
Specified dose on specified days
Other Names:
  • Tegafur-gimeracil-oteracil potassium
Drug: Placebo
Specified dose, once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Progression-free survival (PFS) (site investigator assessment)
Time Frame: up to 2years
up to 2years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: up to 2years
up to 2years
Objective response rate (ORR) (site investigator assessment)
Time Frame: up to 2years
up to 2years
Best overall response (BOR) (site investigator assessment)
Time Frame: up to 2years
up to 2years
Duration of response (DOR) (site investigator assessment)
Time Frame: up to 2years
up to 2years
Disease control rate (DCR) (site investigator assessment)
Time Frame: up to 2years
up to 2years
Time to response (TTR) (site investigator assessment)
Time Frame: up to 2years
up to 2years
Maximum percent change in the sum diameters of the target lesions (site investigator assessment)
Time Frame: up to 2years
up to 2years
Progression-free survival after the next line of therapy (PFS2) (site investigator assessment)
Time Frame: up to 2years
up to 2years
Adverse event (AE)
Time Frame: Up to 30 days after the last dose
Number of participants with treatment-emergent adverse events (TEAEs) as assessed by CTCAE v5.0
Up to 30 days after the last dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ono Pharmaceutical Co. Ltd

Investigators

  • Study Director: Project Leader, Ono Pharmaceutical Co. Ltd

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 10, 2024

Primary Completion (Actual)

October 9, 2025

Study Completion (Estimated)

July 31, 2027

Study Registration Dates

First Submitted

January 23, 2024

First Submitted That Met QC Criteria

February 4, 2024

First Posted (Actual)

February 13, 2024

Study Record Updates

Last Update Posted (Actual)

March 13, 2026

Last Update Submitted That Met QC Criteria

March 11, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ONO-4578-08

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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