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

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
626

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: up to 3 years
(N/A)
up to 3 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ono Pharmaceutical Co., Ltd.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 5, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 20, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 6, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 1, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 3, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 25, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 23, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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