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AzTrials

Colorectal CancerPhase 2NCT06948448

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

A Phase 2 study testing ONO-4578, Opdivo® and Oxaliplatin in people with Colorectal Cancer, run by Ono Pharmaceutical Co., Ltd. at 39 sites in 6 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Cancer
What is being tested?
ONO-4578, Opdivo® and Oxaliplatin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
144 participants
Where
39 sitesin 6 countries
Study dates
18 Nov 2025to 1 Oct 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

39 sites in 6 countries. Contact the study team or a site near you to ask about taking part.

North America Clinical Trial Support Desk contact

+18665877745(Toll-Free)

clinical_trial@ono-pharma.com

International Clinical Trial Support Desk contact

+17162141777(Standard)

clinical_trial@ono-pharma.com

39 sites in 6 countries

United States11 sites, 11 recruiting

  • The Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43221

    Recruiting

  • Mayo Clinic Florida

    Jacksonville, Florida, 32224

    Recruiting

  • Rocky Mountain Cancer Centers, LLP

    Lone Tree, Colorado, 80124

    Recruiting

  • USC Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

    Recruiting

  • Virginia Oncology Associates

    Norfolk, Virginia, 23502

    Recruiting

  • Advent Health

    Orlando, Florida, 32803

    Recruiting

  • Thomas Jefferson University, Sidney Kimmel Cancer Center

    Philadelphia, Pennsylvania, 19107

    Recruiting

  • Mayo Clinic Arizona

    Phoenix, Arizona, 85054

    Recruiting

  • May Clinic Rochester

    Rochester, Minnesota, 55905

    Recruiting

  • Blue Ridge Cancer Care

    Salem, Virginia, 24153

    Recruiting

  • Baylor Scott & White Medical Center

    Temple, Texas, 76508

    Recruiting

Other trials in United States

France8 sites, 8 recruiting

  • CHU Besançon - Hôpital Jean Minjoz

    Besançon, Doubs

    Recruiting

  • Centre Leon Berard

    Lyon, Rhone

    Recruiting

  • Hôpital de la Timone

    Marseille, Marseille

    Recruiting

  • Chru De Nantes Hotel-Dieu

    Nantes, Loire Atlantique

    Recruiting

  • Hôpital Européen Georges Pompidou

    Paris, Paris

    Recruiting

  • Hôpital Saint-Antoine

    Paris, Paris

    Recruiting

  • CHU Bordeaux - Hôpital Haut-Lévêque

    Pessac, Gironde

    Recruiting

  • CHU Poitiers - Hôpital la Milétrie

    Poitiers, Vienne

    Recruiting

Other trials in France

Spain7 sites, 7 recruiting

  • Institut Catala d'Oncologia (H. Germans Trias I Pujol, ICO-Barcelona)

    Badalona, Barcelona

    Recruiting

  • Hosptial Universitari Vall d'Hebron

    Barcelona, Barcelona

    Recruiting

  • Hospital Universitario Reina Sofia

    Córdoba, Córdoba

    Recruiting

  • Hospital Universitario 12 de Octubre

    Madrid, Madrid

    Recruiting

  • Hospital Regional Universitario de Malaga

    Málaga, Spain

    Recruiting

  • Hospital Universitario Virgen del Rocio

    Seville, Sevilla

    Recruiting

  • Hospital General Universitario de Valencia

    Valencia, Valencia

    Recruiting

Other trials in Spain

Italy6 sites, 6 recruiting

  • Azienda Socio Sanitaria Territoriale Niguarda

    Milan, Italy

    Recruiting

  • Istituto Clinico Humanitas

    Milan, Italy

    Recruiting

  • Istituto Europeo di Oncologia

    Milan, Italy

    Recruiting

  • AOU Uni degli Studi Della Campania Lugi Vanvitelli

    Naples, Napoli

    Recruiting

  • Istituto Nazionale Tumori Fondazione G. Pascale

    Naples, Napoli

    Recruiting

  • IOV-Istituto Oncologico

    Padova, Padova

    Recruiting

Other trials in Italy

Japan4 sites, 4 recruiting

  • Kobe City Medical Center General Hospital

    Hyōgo, Kobe-shi

    Recruiting

  • National Hospital Organization Osaka National Hospital

    Osaka, Osaka-shi

    Recruiting

  • Osaka General Medical Center

    Osaka, Osaka-shi

    Recruiting

  • Osaka International Cancer Institute

    Osaka, Osaka-shi

    Recruiting

Other trials in Japan

Canada3 sites, 3 recruiting

  • Jewish General Hospital

    Montreal, Quebec

    Recruiting

  • The Ottawa Hospital Cancer Centre

    Ottawa, Ontario

    Recruiting

  • Princess Margaret Cancer Centre- University Health Network

    Toronto, Ontario, M5G 2M9

    Recruiting

Other trials in Canada

About this study

Official title: 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.

Read the 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.

Being tested
ONO-4578, Opdivo®, Oxaliplatin, 5-Fluorouracil, Bevacizumab
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ONO-4578Drug

    ONO-4578 tablets once a day

  • Opdivo®Drug

    Also called Nivolumab

    Specified dose on specified days

  • OxaliplatinDrug

    Specified dose on specified days

  • 5-FluorouracilDrug

    Specified dose on specified days

  • BevacizumabDrug

    Specified dose on specified days

  • LeucovorinDrug

    Specified dose on specified days

Study groups in NCT06948448
Study groupRoleWhat they receive
Arm A ONO-4578 dose 1 + Opdivo® + SOC (mFOLFOX6 + bevacizumab)ExperimentalNot described
Receives: Drug: ONO-4578; Drug: Opdivo®; Drug: Oxaliplatin; Drug: 5-Fluorouracil; Drug: Bevacizumab; Drug: Leucovorin
Arm B ONO-4578 dose 2 + Opdivo® + SOC (mFOLFOX6 + bevacizumab)ExperimentalNot described
Receives: Drug: ONO-4578; Drug: Opdivo®; Drug: Oxaliplatin; Drug: 5-Fluorouracil; Drug: Bevacizumab; Drug: Leucovorin
Arm C SOC (mFOLFOX6+bevacizumab)Active comparatorNot described
Receives: Drug: Oxaliplatin; Drug: 5-Fluorouracil; Drug: Bevacizumab; Drug: Leucovorin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate (ORR) per Blinded Independent Central Review (BICR)

    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.

    Measured: From randomization to the end of treatment (Up to 39 months)

  2. Number of participants with Adverse Events (AEs)

    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.

    Measured: From first dose to 28 days post last dose

  3. Number of participants with Serious Adverse Events (SAEs)

    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.

    Measured: From first dose to 28 days post last dose

Secondary outcomes (15)

  1. Overall Response Rate (ORR) per Investigator assessment

    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.

    Measured: From randomization to the end of treatment (Up to 39 months)

  2. Overall Survival (OS)

    OS is defined as the time between the date of randomization and the date of death due to any cause.

    Measured: From randomization to the end of treatment (Up to 39 months)

  3. Progression-Free Survival (PFS) by BICR

    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.

    Measured: From randomization to the end of treatment (Up to 39 months)

  4. Progression-Free Survival (PFS) by Investigator assessment

    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.

    Measured: From randomization to the end of treatment (Up to 39 months)

  5. Best overall response (BOR) by BICR

    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.

    Measured: From randomization to the end of treatment (Up to 39 months)

  6. Best overall response (BOR) by Investigator assessment

    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.

    Measured: From randomization to the end of treatment (Up to 39 months)

  7. Duration of response (DOR) by BICR

    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.

    Measured: From randomization to the end of treatment (Up to 39 months)

  8. Duration of response (DOR) by Investigator assessment

    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.

    Measured: From randomization to the end of treatment (Up to 39 months)

  9. Disease Control Rate (DCR) by BICR

    DCR is defined as the percentage of participants whose BOR is determined to be CR, PR, or stable disease (SD).

    Measured: From randomization to the end of treatment (Up to 39 months)

  10. Disease Control Rate (DCR) by Investigator assessment

    DCR is defined as the percentage of participants whose BOR is determined to be CR, PR, or stable disease (SD).

    Measured: From randomization to the end of treatment (Up to 39 months)

  11. Time to Response (TTR) by BICR

    TTR is defined as the time from the date of randomization to the date of first confirmed CR or PR.

    Measured: From randomization to the end of treatment (Up to 39 months)

  12. Time to Response (TTR) by Investigator assessment

    TTR is defined as the time from the date of randomization to the date of first confirmed CR or PR.

    Measured: From randomization to the end of treatment (Up to 39 months)

  13. Maximum percent change in the sum of the diameters of the target lesions by BICR

    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.

    Measured: From randomization to the end of treatment (Up to 39 months)

  14. Maximum percent change in the sum of the diameters of the target lesions by Investigator assessment

    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.

    Measured: From randomization to the end of treatment (Up to 39 months)

  15. Progression-Free Survival of second line therapy (PFS2) by Investigator assessment

    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.

    Measured: From randomization to the end of treatment (Up to 39 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Apr 2025
  2. Study start18 Nov 2025
  3. Primary completion15 Feb 2028 (estimated)
  4. Study completion1 Oct 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
144 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06948448
Sponsor's protocol ID
ONO-4578-10
Other IDs
jRCT2051250119
Status last verified
Jul 2026
First submitted
21 Apr 2025
Last updated
16 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ONO-4578, Opdivo® and Oxaliplatin in people with Colorectal Cancer, run by Ono Pharmaceutical Co., Ltd. at 39 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 16 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 39 sites in United States, France, Spain, Italy, Japan and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact North America Clinical Trial Support Desk (+18665877745(Toll-Free), clinical_trial@ono-pharma.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) per Blinded Independent Central Review (BICR) (time frame: From randomization to the end of treatment (Up to 39 months)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06948448.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2026.

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