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

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Investigational drug late phase More information Active drug More information Moderate burden on patient More information

Trial Details

Sponsor: Ono Pharmaceutical Co. Ltd (industry)

Phase: 2

Start date: Nov. 18, 2025

Planned enrollment: 144

Trial ID: NCT06948448
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More trial details at ClinicalTrials.gov More info

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Investigational Drug AI Analysis

chevron Show for: ONO-4578 (BMS-986310)

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Goal: Evaluate whether adding either of two doses of ONO-4578 plus nivolumab to first-line mFOLFOX6 and bevacizumab improves outcomes in advanced colorectal cancer, while assessing safety.

Patients: Adults with unresectable locally advanced or metastatic colorectal cancer, centrally confirmed PD-L1-positive tumors, ECOG performance status 0–1, and no prior systemic therapy for advanced disease. MSI-high/dMMR tumors and BRAF V600E mutations are excluded, as are prior immune-checkpoint therapy and certain autoimmune or pulmonary conditions.

Design: Randomized, open-label, multicenter study assigning participants 1:1:1 to two investigational regimens or an active-control regimen. Treatment is given in 28-day cycles until progression, unacceptable toxicity, investigator decision, consent withdrawal, or study termination.

Treatments: The two investigational arms add different doses of ONO-4578 and nivolumab to mFOLFOX6 plus bevacizumab; the control arm receives mFOLFOX6 plus bevacizumab. ONO-4578 is an oral antagonist of the prostaglandin E2 receptor EP4, intended to reduce immunosuppressive signaling and complement PD-1 blockade by nivolumab. In a separate phase 2 trial in gastric or gastroesophageal junction cancer, adding ONO-4578 to nivolumab and chemotherapy yielded median progression-free survival of 9.0 versus 6.9 months and response rates of 62.0% versus 48.7%; these results do not establish benefit in colorectal cancer. mFOLFOX6 combines oxaliplatin, fluorouracil, and leucovorin, with bevacizumab as the standard-of-care comparator regimen.

Outcomes: Primary measures are confirmed objective response rate by blinded independent central review under RECIST 1.1 and the numbers of participants with adverse events and serious adverse events. Secondary measures include investigator-assessed response, overall and progression-free survival, duration and timing of response, disease control, tumor-size change, and progression-free survival through subsequent therapy. Efficacy assessments extend up to 39 months; adverse events are collected through 28 days after the last dose.

Burden on patient: Likely moderate relative to standard first-line chemotherapy. All participants receive a multidrug infusion regimen and undergo response imaging and safety monitoring; investigational-arm participants also take oral ONO-4578 and receive nivolumab, potentially increasing treatment time, monitoring, and toxicity-related visits. Central PD-L1 testing is required, but the provided information does not specify extra biopsies, intensive pharmacokinetic sampling, or a scan schedule.

Last updated: Sep 2026

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Sites (28)

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Princess Margaret Cancer Centre- University Health Network

Toronto, Ontario, M5G 2M9, Canada

No email / No phone

Status: Recruiting

CHU Besançon - Hôpital Jean Minjoz

Besançon, Doubs, France

No email / No phone

Status: Recruiting

CHU Bordeaux - Hôpital Haut-Lévêque

Pessac, Gironde, France

No email / No phone

Status: Recruiting

Chru De Nantes Hotel-Dieu

Nantes, Loire Atlantique, France

No email / No phone

Status: Recruiting

Hôpital de la Timone

Marseille, Marseille, France

No email / No phone

Status: Recruiting

Hôpital Européen Georges Pompidou

Paris, Paris, France

No email / No phone

Status: Recruiting

Hôpital Saint-Antoine

Paris, Paris, France

No email / No phone

Status: Recruiting

Centre Leon Berard

Lyon, Rhone, France

No email / No phone

Status: Recruiting

CHU Poitiers - Hôpital la Milétrie

Poitiers, Vienne, France

No email / No phone

Status: Recruiting

Istituto Clinico Humanitas

Milan, Italy, Italy

No email / No phone

Status: Recruiting

Istituto Europeo di Oncologia

Milan, Italy, Italy

No email / No phone

Status: Recruiting

Kobe City Medical Center General Hospital

Hyōgo, Kobe-shi, Japan

No email / No phone

Status: Recruiting

National Hospital Organization Osaka National Hospital

Osaka, Osaka-shi, Japan

No email / No phone

Status: Recruiting

Osaka General Medical Center

Osaka, Osaka-shi, Japan

No email / No phone

Status: Recruiting

Osaka International Cancer Institute

Osaka, Osaka-shi, Japan

No email / No phone

Status: Recruiting

Hospital Universitario Reina Sofia

Córdoba, Córdoba, Spain

No email / No phone

Status: Recruiting

Hospital Universitario 12 de Octubre

Madrid, Madrid, Spain

No email / No phone

Status: Recruiting

Hospital Universitario Virgen del Rocio

Seville, Sevilla, Spain

No email / No phone

Status: Recruiting

Hospital General Universitario de Valencia

Valencia, Valencia, Spain

No email / No phone

Status: Recruiting

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

No email / No phone

Status: Recruiting

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

No email / No phone

Status: Recruiting

Rocky Mountain Cancer Centers, LLP

Lone Tree, Colorado, 80124, United States

No email / No phone

Status: Recruiting

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

No email / No phone

Status: Recruiting

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43221, United States

No email / No phone

Status: Recruiting

Thomas Jefferson University, Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania, 19107, United States

No email / No phone

Status: Recruiting

Baylor Scott & White Medical Center

Temple, Texas, 76508, United States

No email / No phone

Status: Recruiting

Blue Ridge Cancer Care

Salem, Virginia, 24153, United States

No email / No phone

Status: Recruiting

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

No email / No phone

Status: Recruiting

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