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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

RecruitingPhase 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

Who can join

Ages 18 and older · All sexes

Full eligibility criteria
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

About the study

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.

What is being tested

Sponsor: Ono Pharmaceutical Co., Ltd. · Participants: 144 · Started: Nov 18, 2025

Contact the study team

Official record on ClinicalTrials.gov — NCT06948448

Locations in the U.S.

ArizonaMayo Clinic Arizona, Phoenix
CaliforniaUSC Norris Comprehensive Cancer Center, Los Angeles
ColoradoRocky Mountain Cancer Centers, LLP, Lone Tree
FloridaMayo Clinic Florida, Jacksonville
Advent Health, Orlando
MinnesotaMay Clinic Rochester, Rochester
OhioThe Ohio State University Comprehensive Cancer Center, Columbus
PennsylvaniaThomas Jefferson University, Sidney Kimmel Cancer Center, Philadelphia
TexasBaylor Scott & White Medical Center, Temple
VirginiaVirginia Oncology Associates, Norfolk
Blue Ridge Cancer Care, Salem

Conditions

From ClinicalTrials.gov, data retrieved Sep 29, 2026. Each study sets its own eligibility; the study team decides who can join.