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

Ono Pharmaceuticals

Status and phase: Begins enrollment in 2 months; Phase 2

Conditions: Colorectal Cancer

Treatments: Drug: 5-Fluorouracil; Drug: Opdivo®; Drug: Bevacizumab; Drug: Leucovorin; Drug: Oxaliplatin; Drug: ONO-4578

Study type: Interventional

Funder types: Industry

Identifiers

NCT06948448

ONO-4578-10

Details and patient eligibility

About

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.

Full 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.

Enrollment: 144 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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144 participants in 3 patient groups

Arm A ONO-4578 dose 1 + Opdivo® + SOC (mFOLFOX6 + bevacizumab)

Experimental group

Treatment:

Drug: Oxaliplatin

Drug: ONO-4578

Drug: Leucovorin

Drug: Bevacizumab

Drug: Opdivo®

Drug: 5-Fluorouracil

Arm B ONO-4578 dose 2 + Opdivo® + SOC (mFOLFOX6 + bevacizumab)

Experimental group

Treatment:

Drug: Oxaliplatin

Drug: ONO-4578

Drug: Leucovorin

Drug: Bevacizumab

Drug: Opdivo®

Drug: 5-Fluorouracil

Arm C SOC (mFOLFOX6+bevacizumab)

Active Comparator group

Treatment:

Drug: Oxaliplatin

Drug: Leucovorin

Drug: Bevacizumab

Drug: 5-Fluorouracil