A Study to Evaluate the Safety and Efficacy of Two Dose Levels of ONO-4578 With Opdivo®, in Combination With mFOLFOX6 and Bevacizumab Versus Standard of Care in Participants With Non-MSI-H/dMMR, PD-L1 Positive Advanced Colorectal Cancer

July 15, 2026 updated by: Ono Pharmaceutical Co., Ltd.

A Randomized, Open Label, Multicenter, Phase 2 Study to Evaluate the Safety and Efficacy of Two Dose Levels of ONO-4578 With Opdivo® in Combination With mFOLFOX6 and Bevacizumab Versus Standard of Care for First-line Treatment of Non-MSI-H/dMMR, PD-L1 Positive Advanced Colorectal Cancer

The purpose of this study is to evaluate the safety and efficacy of two dose levels of ONO-4578 with Opdivo® when added to mFOLFOX6 and bevacizumab versus SOC as first-line treatment for advanced CRC.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
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.

Detailed Description

Potential participants will be consented and screened for study eligibility. Eligible participants will be randomized in a 1:1:1 ratio to one of the three study intervention arms. Study intervention will be administered in 28-day treatment cycles and continued until disease progression, intolerable toxicity, Investigator decision or withdrawal of consent by the participant, or termination of the study by the Sponsor.

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 (Estimated)

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.
144

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 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 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 Contact Backup

Study Locations

  • Canada
    • Ontario
      • Ottawa, Ontario, Canada
        • Recruiting
        • The Ottawa Hospital Cancer Centre
      • Toronto, Ontario, Canada, M5G 2M9
        • Recruiting
        • Princess Margaret Cancer Centre- University Health Network
    • Quebec
      • Montreal, Quebec, Canada
        • Recruiting
        • Jewish General Hospital
  • France
    • Doubs
      • Besançon, Doubs, France
        • Recruiting
        • CHU Besançon - Hôpital Jean Minjoz
    • Gironde
      • Pessac, Gironde, France
        • Recruiting
        • CHU Bordeaux - Hôpital Haut-Lévêque
    • Loire Atlantique
      • Nantes, Loire Atlantique, France
        • Recruiting
        • Chru De Nantes Hotel-Dieu
    • Marseille
      • Marseille, Marseille, France
        • Recruiting
        • Hôpital de la Timone
    • Paris
      • Paris, Paris, France
        • Recruiting
        • Hôpital Europeén Georges Pompidou
      • Paris, Paris, France
        • Recruiting
        • Hôpital Saint-Antoine
    • Rhone
      • Lyon, Rhone, France
        • Recruiting
        • Centre Léon Bérard
    • Vienne
      • Poitiers, Vienne, France
        • Recruiting
        • CHU Poitiers - Hôpital la Milétrie
  • Italy
    • Italy
      • Milan, Italy, Italy
        • Recruiting
        • Istituto Europeo di Oncologia
      • Milan, Italy, Italy
        • Recruiting
        • Istituto Clinico Humanitas
      • Milan, Italy, Italy
        • Recruiting
        • Azienda Socio Sanitaria Territoriale Niguarda
    • Napoli
      • Naples, Napoli, Italy
        • Recruiting
        • Istituto Nazionale Tumori Fondazione G. Pascale
      • Naples, Napoli, Italy
        • Recruiting
        • AOU Uni degli Studi Della Campania Lugi Vanvitelli
    • Padova
      • Padova, Padova, Italy
        • Recruiting
        • IOV-Istituto Oncologico
  • Japan
    • Kobe-shi
      • Hyōgo, Kobe-shi, Japan
        • Recruiting
        • Kobe City Medical Center General Hospital
    • Osaka-shi
      • Osaka, Osaka-shi, Japan
        • Recruiting
        • National Hospital Organization Osaka National Hospital
      • Osaka, Osaka-shi, Japan
        • Recruiting
        • Osaka General Medical Center
      • Osaka, Osaka-shi, Japan
        • Recruiting
        • Osaka International Cancer Institute
  • Spain
    • Barcelona
      • Badalona, Barcelona, Spain
        • Recruiting
        • Institut Catala d'Oncologia (H. Germans Trias I Pujol, ICO-Barcelona)
      • Barcelona, Barcelona, Spain
        • Recruiting
        • Hosptial Universitari Vall d'Hebron
    • Córdoba
      • Córdoba, Córdoba, Spain
        • Recruiting
        • Hospital Universitario Reina Sofia
    • Madrid
      • Madrid, Madrid, Spain
        • Recruiting
        • Hospital Universitario 12 de Octubre
    • Sevilla
      • Seville, Sevilla, Spain
        • Recruiting
        • Hospital Universitario Virgen del Rocío
    • Spain
      • Málaga, Spain, Spain
        • Recruiting
        • Hospital Regional Universitario de Málaga
    • Valencia
      • Valencia, Valencia, Spain
        • Recruiting
        • Hospital General Universitario de Valencia
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Recruiting
        • Mayo Clinic Arizona
    • California
      • Los Angeles, California, United States, 90033
        • Recruiting
        • USC Norris Comprehensive Cancer Center
    • Colorado
      • Lone Tree, Colorado, United States, 80124
        • Recruiting
        • Rocky Mountain Cancer Centers, LLP
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Mayo Clinic Florida
      • Orlando, Florida, United States, 32803
        • Recruiting
        • Advent Health
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • May Clinic Rochester
    • Ohio
      • Columbus, Ohio, United States, 43221
        • Recruiting
        • The Ohio State University Comprehensive Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Thomas Jefferson University, Sidney Kimmel Cancer Center
    • Texas
      • Temple, Texas, United States, 76508
        • Recruiting
        • Baylor Scott & White Medical Center
    • Virginia
      • Norfolk, Virginia, United States, 23502
        • Recruiting
        • Virginia Oncology Associates
      • Salem, Virginia, United States, 24153
        • Recruiting
        • Blue Ridge Cancer Care

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically confirmed advanced (locally advanced or metastatic) colorectal cancer not amenable to curative resection
  • ECOG Performance Status of 0-1
  • No prior systemic treatment for advanced local or mCRC
  • Participants whose tumor is positive for PD-L1 expression as determined at a central laboratory

Exclusion Criteria:

  • Participants with high microsatellite instability (MSI-High), or mismatch repair deficient (dMMR) tumor
  • Participants with BRAF V600E mutation
  • Unable to swallow tablets.
  • Participants with complication or history of interstitial lung disease, pneumonitis or pulmonary fibrosis
  • Participants with an active, known or suspected autoimmune disease.
  • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.

Other protocol-defined inclusion/exclusion criteria apply

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.
Experimental: Arm A ONO-4578 dose 1 + Opdivo® + SOC (mFOLFOX6 + bevacizumab)
Drug: Oxaliplatin
Specified dose on specified days
Drug: Leucovorin
Specified dose on specified days
Drug: Bevacizumab
Specified dose on specified days
Drug: ONO-4578
ONO-4578 tablets once a day
Drug: Opdivo®
Specified dose on specified days
Other Names:
  • Nivolumab
Drug: 5-Fluorouracil
Specified dose on specified days
Experimental: Arm B ONO-4578 dose 2 + Opdivo® + SOC (mFOLFOX6 + bevacizumab)
Drug: Oxaliplatin
Specified dose on specified days
Drug: Leucovorin
Specified dose on specified days
Drug: Bevacizumab
Specified dose on specified days
Drug: ONO-4578
ONO-4578 tablets once a day
Drug: Opdivo®
Specified dose on specified days
Other Names:
  • Nivolumab
Drug: 5-Fluorouracil
Specified dose on specified days
Active Comparator: Arm C SOC (mFOLFOX6+bevacizumab)
Drug: Oxaliplatin
Specified dose on specified days
Drug: Leucovorin
Specified dose on specified days
Drug: Bevacizumab
Specified dose on specified days
Drug: 5-Fluorouracil
Specified dose on specified days

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 Response Rate (ORR) per Blinded Independent Central Review (BICR)
Time Frame: From randomization to the end of treatment (Up to 39 months)
ORR (assessed by BICR per RECIST v1.1) is defined as the proportion of participants with a BOR of confirmed CR or PR. The ORR will be estimated as the number of participants achieving BOR of CR or PR assessed by BICR per RECIST v1.1 divided by the total number of participants.
From randomization to the end of treatment (Up to 39 months)
Number of participants with Adverse Events (AEs)
Time Frame: From first dose to 28 days post last dose
An AE is any untoward medical occurrence in a patient or clinical study patient, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.
From first dose to 28 days post last dose
Number of participants with Serious Adverse Events (SAEs)
Time Frame: From first dose to 28 days post last dose
SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in significant disability/incapacity.
From first dose to 28 days post last dose

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
Overall Response Rate (ORR) per Investigator assessment
Time Frame: From randomization to the end of treatment (Up to 39 months)
ORR (assessed by site Investigator per RECIST v1.1) is defined as the proportion of participants with a BOR of confirmed CR or PR. The ORR will be estimated as the number of participants achieving BOR of CR or PR assessed by site Investigator per RECIST v1.1 divided by the total number of participants.
From randomization to the end of treatment (Up to 39 months)
Overall Survival (OS)
Time Frame: From randomization to the end of treatment (Up to 39 months)
OS is defined as the time between the date of randomization and the date of death due to any cause.
From randomization to the end of treatment (Up to 39 months)
Progression-Free Survival (PFS) by BICR
Time Frame: From randomization to the end of treatment (Up to 39 months)
PFS by BICR is defined as the time from date of randomization to the date of the first documented progressive disease (PD) as determined by BICR per RECIST version 1.1, or the date of death due to any cause, whichever occurs first.
From randomization to the end of treatment (Up to 39 months)
Progression-Free Survival (PFS) by Investigator assessment
Time Frame: From randomization to the end of treatment (Up to 39 months)
PFS by Investigator assessment is defined as the time from date of randomization to the date of the first documented progressive disease (PD) as determined by site Investigator per RECIST version 1.1, or the date of death due to any cause, whichever occurs first.
From randomization to the end of treatment (Up to 39 months)
Best overall response (BOR) by BICR
Time Frame: From randomization to the end of treatment (Up to 39 months)
BOR is defined as the best response designation, recorded between the start of the study intervention and the date of the initial objectively documented PD per RECIST v1.1 or the date of subsequent anti-cancer therapy, whichever occurs first.
From randomization to the end of treatment (Up to 39 months)
Best overall response (BOR) by Investigator assessment
Time Frame: From randomization to the end of treatment (Up to 39 months)
BOR is defined as the best response designation, recorded between the start of the study intervention and the date of the initial objectively documented PD per RECIST v1.1 or the date of subsequent anti-cancer therapy, whichever occurs first.
From randomization to the end of treatment (Up to 39 months)
Duration of response (DOR) by BICR
Time Frame: From randomization to the end of treatment (Up to 39 months)
DOR is defined as the time between the date of first confirmed CR or PR to the date of the first documented PD per RECIST v1.1 or death due to any cause, whichever occurs first.
From randomization to the end of treatment (Up to 39 months)
Duration of response (DOR) by Investigator assessment
Time Frame: From randomization to the end of treatment (Up to 39 months)
DOR is defined as the time between the date of first confirmed CR or PR to the date of the first documented PD per RECIST v1.1 or death due to any cause, whichever occurs first.
From randomization to the end of treatment (Up to 39 months)
Disease Control Rate (DCR) by BICR
Time Frame: From randomization to the end of treatment (Up to 39 months)
DCR is defined as the percentage of participants whose BOR is determined to be CR, PR, or stable disease (SD).
From randomization to the end of treatment (Up to 39 months)
Disease Control Rate (DCR) by Investigator assessment
Time Frame: From randomization to the end of treatment (Up to 39 months)
DCR is defined as the percentage of participants whose BOR is determined to be CR, PR, or stable disease (SD).
From randomization to the end of treatment (Up to 39 months)
Time to Response (TTR) by BICR
Time Frame: From randomization to the end of treatment (Up to 39 months)
TTR is defined as the time from the date of randomization to the date of first confirmed CR or PR.
From randomization to the end of treatment (Up to 39 months)
Time to Response (TTR) by Investigator assessment
Time Frame: From randomization to the end of treatment (Up to 39 months)
TTR is defined as the time from the date of randomization to the date of first confirmed CR or PR.
From randomization to the end of treatment (Up to 39 months)
Maximum percent change in the sum of the diameters of the target lesions by BICR
Time Frame: From randomization to the end of treatment (Up to 39 months)
In participants who have target lesions at baseline and at least 1 post-baseline imaging evaluation, the maximum percent change in the sum of diameters of target lesions is the percent change at the point of the minimum sum of diameters of the target lesions.
From randomization to the end of treatment (Up to 39 months)
Maximum percent change in the sum of the diameters of the target lesions by Investigator assessment
Time Frame: From randomization to the end of treatment (Up to 39 months)
In participants who have target lesions at baseline and at least 1 post-baseline imaging evaluation, the maximum percent change in the sum of diameters of target lesions is the percent change at the point of the minimum sum of diameters of the target lesions.
From randomization to the end of treatment (Up to 39 months)
Progression-Free Survival of second line therapy (PFS2) by Investigator assessment
Time Frame: From randomization to the end of treatment (Up to 39 months)
PFS2 is defined as the time from date of randomization to the date of an overall response of PD after subsequent anti-cancer therapy, initiating date of a second subsequent anti-cancer therapy, or date of death from any cause, whichever occurs first.
From randomization to the end of treatment (Up to 39 months)

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 18, 2025

Primary Completion (Estimated)

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.
February 15, 2028

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.
October 1, 2028

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).
April 21, 2025

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.
April 21, 2025

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.
April 29, 2025

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.
July 16, 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.
July 15, 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.
July 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-4578-10
  • jRCT2051250119 (Registry Identifier: jRCT)

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

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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