A Study to Evaluate the Efficacy and Safety of ONO-4538 in Combination With Ipilimumab and Chemotherapy in Chemotherapy-naïve Participants With HER2-negative Unresectable Advanced or Recurrent Gastric Cancer (Including Esophagogastric Junction Cancer)

June 23, 2026 updated by: Ono Pharmaceutical Co., Ltd.

A Randomized, Multicenter, Open-label, Phase III Study to Compare the Efficacy and Safety of ONO-4538 in Combination With Ipilimumab, Fluoropyrimidine-based and Platinum-based Chemotherapy (Hereinafter Referred to as "Chemotherapy") Versus 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 ONO-4538 in combination with ipilimumab and chemotherapy versus 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)

626

Phase

  • Phase 3

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
    • Chiba
      • Kashiwa-shi, Chiba, Japan
        • National Cancer Center Hospital East
    • Kanagawa
      • Yokohama, Kanagawa, Japan
        • Kanagawa Cancer Center
    • Miyagi
      • Osaki-shi, Miyagi, Japan
        • Osaki Citizen Hospital
    • Osaka
      • Suita-shi, Osaka, Japan
        • Osaka University Hospital
    • Saitama
      • Hidaka-shi, Saitama, Japan
        • Saitama Medical University International Medical Center
      • Ina-machi, Kitaadati-gun, Saitama, Japan
        • Saitama Cancer Center
    • Shizuoka
      • Nagaizumi-Cho, Sunto-Gun, Shizuoka, Japan
        • Shizuoka Cancer Center
    • Tokyo
      • Bunkyo-ku, Tokyo, Japan
        • University of Tokyo Hospital
      • Chuo-ku, Tokyo, Japan
        • National Cancer Center Hospital
      • Koto-ku, Tokyo, Japan
        • Cancer Institute Hospital of Jfcr
      • Minato-ku, Tokyo, Japan
        • IMSUT Hospital, The Institute of Medical Science, The University of Tokyo
      • Shinjyuku-ku, Tokyo, Japan
        • Keio University Hospital
  • South Korea
      • Busan, South Korea
        • Dong-A University Hospital
      • Busan, South Korea
        • Inje university Haeundae Paik Hospital
      • Busan, South Korea
        • Pusan National University Hospital
      • Daegu, South Korea
        • Keimyung University Dongsan Hospital
      • Daejeon, South Korea
        • Chungnam National University Hospital
      • Daejeon, South Korea
        • Konyang University Hospital
      • Incheon, South Korea
        • Gachon University Gil Medical Center
      • 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
        • Seoul National University Hospital
      • Seoul, South Korea
        • Severance Hospital, Yonsei University Health System
      • Seoul, South Korea
        • The Catholic University of Korea, Seoul St. Mary's Hospital
      • Seoul, South Korea
        • Gangnam Severance Hospital, Yonsei University Health System
      • Seoul, South Korea
        • Chung-Ang 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
    • Gyeongsangbuk-do
      • Daegu, Gyeongsangbuk-do, South Korea
        • Kyungpook National University Chilgok 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
      • Kaohsiung City, Taiwan
        • Kaohsiung Chang Gung Memorial Hospital
      • Keelung, Taiwan
        • Chang Gung Memorial Hospital, Keelung
      • New Taipei City, Taiwan
        • Far Eastern Memorial Hospital
      • New Taipei City, Taiwan
        • Taipei Medical University - Shuang Ho Hospital, Ministry of Health and Welfare
      • Taichung, Taiwan
        • China Medical University Hospital
      • Taichung, Taiwan
        • Taichung Veterans General Hospital
      • Tainan, Taiwan
        • National Cheng Kung University Hospital
      • Tainan, Taiwan
        • Chi Mei Hospital, Liouying
      • Taipei, Taiwan
        • Tri-Service General Hospital
      • Taipei, Taiwan
        • National Taiwan University Hospital
      • Taipei, Taiwan
        • Taipei Veterans General Hospital
      • Taipei, Taiwan
        • Taipei Medical University Hospital
      • Taipei, Taiwan
        • Koo Foundation Sun Yat-Sen Cancer Center
      • Taipei, Taiwan
        • Taipei Municipal Wanfang Hospital Managed by Taipei Medical University
      • Taoyuan County, 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

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Participants with unresectable advanced or recurrent gastric cancer (including esophagogastric junction cancer) that has been histologically confirmed to be predominant adenocarcinoma
  2. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score 0 or 1
  3. Participants who have a life expectancy of at least 3 months

Exclusion Criteria:

  1. Participants with a history or complications of multiple cancers
  2. Participants with a complication or history of severe hypersensitivity to any other antibody products
  3. Participants with concurrent autoimmune disease or a history of chronic or recurrent autoimmune disease.

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: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Chemotherapy
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
Experimental: ONO-4538 + ipilimumab + chemotherapy
Drug: Ipilimumab
Specified dose on specified days
Other Names:
  • BMS-734016
  • Yervoy
Drug: Oxaliplatin
Specified dose on specified days
Drug: Capecitabine
Specified dose on specified days
Drug: ONO-4538
Specified dose on specified days
Other Names:
  • Opdivo
  • Nivolumab
Drug: S-1
Specified dose on specified days
Other Names:
  • Tegafur-gimeracil-oteracil potassium

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: up to 3 years
(N/A)
up to 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS) (site investigator assessment)
Time Frame: up to 3 years
(N/A)
up to 3 years
Objective response rate (ORR) (site investigator assessment)
Time Frame: up to 3 years
(N/A)
up to 3 years
Best overall response (BOR) (site investigator assessment)
Time Frame: up to 3 years
(N/A)
up to 3 years
Duration of response (DOR) (site investigator assessment)
Time Frame: up to 3 years
(N/A)
up to 3 years
Disease control rate (DCR) (site investigator assessment)
Time Frame: up to 3 years
(N/A)
up to 3 years
Time to response (TTR) (site investigator assessment)
Time Frame: up to 3 years
(N/A)
up to 3 years
Maximum percent change in the sum diameters of the target lesions (site investigator assessment)
Time Frame: up to 3 years
(N/A)
up to 3 years
Progression-free survival after the next line of therapy (PFS2) (site investigator assessment)
Time Frame: up to 3 years
(N/A)
up to 3 years
Adverse event
Time Frame: Up to 30 days after the last dose
(N/A)
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)

November 5, 2021

Primary Completion (Actual)

October 20, 2025

Study Completion (Estimated)

May 1, 2027

Study Registration Dates

First Submitted

October 6, 2021

First Submitted That Met QC Criteria

December 1, 2021

First Posted (Actual)

December 3, 2021

Study Record Updates

Last Update Posted (Actual)

June 25, 2026

Last Update Submitted That Met QC Criteria

June 23, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ONO-4538-113

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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