RecruitingInterventionalPhase 2

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

NCT ID: NCT06948448Sponsor: Ono Pharmaceutical Co., Ltd.Last updated: 2026-06-15

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.

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.

Arms & interventions

DrugONO-4578
ONO-4578 tablets once a day
DrugOpdivo®
Specified dose on specified days
DrugOxaliplatin
Specified dose on specified days
Drug5-Fluorouracil
Specified dose on specified days
DrugBevacizumab
Specified dose on specified days
DrugLeucovorin
Specified dose on specified days

Outcome measures

Primary

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.
Time frame: From randomization to the end of treatment (Up to 39 months)
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.
Time frame: From first dose to 28 days post last dose
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.
Time frame: From first dose to 28 days post last dose

Secondary

Overall Response Rate (ORR) per Investigator assessment
Time frame: 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)
Progression-Free Survival (PFS) by BICR
Time frame: 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)
Best overall response (BOR) by BICR
Time frame: 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)
Duration of response (DOR) by BICR
Time frame: 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)
Disease Control Rate (DCR) by BICR
Time frame: 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)
Time to Response (TTR) by BICR
Time frame: 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)
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)
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)
Progression-Free Survival of second line therapy (PFS2) by Investigator assessment
Time frame: From randomization to the end of treatment (Up to 39 months)

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

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 locations (11)

Mayo Clinic Arizona

Phoenix, Arizona, 85054

Recruiting

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033

Recruiting

Rocky Mountain Cancer Centers, LLP

Lone Tree, Colorado, 80124

Recruiting

Mayo Clinic Florida

Jacksonville, Florida, 32224

Recruiting

Advent Health

Orlando, Florida, 32803

Recruiting

May Clinic Rochester

Rochester, Minnesota, 55905

Recruiting

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43221

Recruiting

Thomas Jefferson University, Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania, 19107

Recruiting

Baylor Scott & White Medical Center

Temple, Texas, 76508

Recruiting

Virginia Oncology Associates

Norfolk, Virginia, 23502

Recruiting

Blue Ridge Cancer Care

Salem, Virginia, 24153

Recruiting