Home › Trials › NCT06948448

Two-dose ONO-4578 with Opdivo plus mFOLFOX6 and bevacizumab versus standard treatment for advanced PD-L1–positive 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

Phase 2 Interventional Ono Pharmaceutical Co., Ltd. · NCT06948448

This trial tests whether adding one of two doses of ONO-4578 to Opdivo, standard chemotherapy (mFOLFOX6), and bevacizumab helps people with PD-L1–positive, non-MSI-H advanced colorectal cancer as their first-line treatment.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment144 (estimated)
Ages18 Years and up
SexAll
SponsorOno Pharmaceutical Co., Ltd. Industry-sponsored
Drugs / interventionsbevacizumab
Locations28 sites (Phoenix, Arizona and 27 other locations)
Trial IDNCT06948448 on ClinicalTrials.gov

What this trial studies

Eligible participants with PD-L1–positive, non-MSI-H/dMMR advanced colorectal cancer are randomized 1:1:1 to receive one of two dose levels of ONO-4578 plus Opdivo with mFOLFOX6 and bevacizumab or to receive the current standard-of-care regimen. Treatments are given in 28-day cycles and continued until disease progression, intolerable toxicity, investigator decision, withdrawal of consent, or sponsor termination. Key entry requirements include ECOG 0–1, no prior systemic therapy for advanced disease, PD-L1 positivity confirmed at a central lab, and exclusion of MSI-High/dMMR or BRAF V600E mutated tumors. Safety and anti-tumor activity endpoints will compare the combination arms against standard care to determine whether the addition of ONO-4578 improves outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically confirmed advanced (unresectable or metastatic) colorectal cancer that is PD-L1–positive, non-MSI-H/dMMR, ECOG 0–1, and who have not received prior systemic treatment for advanced disease.

Not a fit: Patients with MSI-High/dMMR tumors, BRAF V600E mutations, prior checkpoint inhibitor therapy, active autoimmune disease, or poor performance status are unlikely to be eligible or to benefit from this regimen.

Why it matters

Potential benefit: If successful, the combination could increase response rates or prolong survival compared with current first-line therapy for PD-L1–positive, non-MSI-H advanced colorectal cancer.

How similar studies have performed: Checkpoint inhibitors alone have not shown consistent benefit in non-MSI-H colorectal cancer, so combining a novel agent like ONO-4578 with PD-1 blockade and chemotherapy is a relatively novel approach with uncertain but potentially meaningful outcomes.

Eligibility criteria

Show full inclusion / exclusion 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

Where this trial is running

Phoenix, Arizona and 27 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Colorectal Cancer
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.