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 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.

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.

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