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NCT06948448PHASE2Recruiting

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 Pharmaceutical Co., Ltd.

Start Date

11/18/2025

Completion Date

10/1/2028

Summary

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.

Detailed 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.

Eligibility Criteria

Age Range: 18 years to No maximum

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

Interventions

DRUG

ONO-4578

DRUG

Opdivo®

DRUG

Oxaliplatin

DRUG

5-Fluorouracil

DRUG

Bevacizumab

DRUG

Leucovorin

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Conditions

Colorectal Cancer

Locations

Mayo Clinic Arizona

Phoenix, Arizona 85054

United States

USC Norris Comprehensive Cancer Center

Los Angeles, California 90033

United States

Rocky Mountain Cancer Centers, LLP

Lone Tree, Colorado 80124

United States

Mayo Clinic Florida

Jacksonville, Florida 32224

United States

Advent Health

Orlando, Florida 32803

United States

May Clinic Rochester

Rochester, Minnesota 55905

United States

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio 43221

United States

Thomas Jefferson University, Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania 19107

United States

Baylor Scott & White Medical Center

Temple, Texas 76508

United States

Virginia Oncology Associates

Norfolk, Virginia 23502

United States

Blue Ridge Cancer Care

Salem, Virginia 24153

United States

The Ottawa Hospital Cancer Centre

Ottawa, Ontario

Canada

Princess Margaret Cancer Centre- University Health Network

Toronto, Ontario M5G 2M9

Canada

Jewish General Hospital

Montreal, Quebec

Canada

CHU Besançon - Hôpital Jean Minjoz

Besançon, Doubs

France

CHU Bordeaux - Hôpital Haut-Lévêque

Pessac, Gironde

France

Chru De Nantes Hotel-Dieu

Nantes, Loire Atlantique

France

Hôpital de la Timone

Marseille, Marseille

France

Hôpital Européen Georges Pompidou

Paris, Paris

France

Hôpital Saint-Antoine

Paris, Paris

France

Centre Leon Berard

Lyon, Rhone

France

CHU Poitiers - Hôpital la Milétrie

Poitiers, Vienne

France

Azienda Socio Sanitaria Territoriale Niguarda

Milan, Italy

Italy

Istituto Clinico Humanitas

Milan, Italy

Italy

Istituto Europeo di Oncologia

Milan, Italy

Italy

AOU Uni degli Studi Della Campania Lugi Vanvitelli

Naples, Napoli

Italy

Istituto Nazionale Tumori Fondazione G. Pascale

Naples, Napoli

Italy

IOV-Istituto Oncologico

Padova, Padova

Italy

Kobe City Medical Center General Hospital

Hyōgo, Kobe-shi

Japan

National Hospital Organization Osaka National Hospital

Osaka, Osaka-shi

Japan

Osaka General Medical Center

Osaka, Osaka-shi

Japan

Osaka International Cancer Institute

Osaka, Osaka-shi

Japan

Institut Catala d'Oncologia (H. Germans Trias I Pujol, ICO-Barcelona)

Badalona, Barcelona

Spain

Hosptial Universitari Vall d'Hebron

Barcelona, Barcelona

Spain

Hospital Universitario Reina Sofia

Córdoba, Córdoba

Spain

Hospital Universitario 12 de Octubre

Madrid, Madrid

Spain

Hospital Universitario Virgen del Rocio

Seville, Sevilla

Spain

Hospital Regional Universitario de Malaga

Málaga, Spain

Spain

Hospital General Universitario de Valencia

Valencia, Valencia

Spain