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

NCT06948448 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: ONO-4578-10
• Study Type: interventional
• Target: 144
• Locations: 6 countries
• Sites: 28

Brief 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.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (3)

• Overall Response Rate (ORR) per Blinded Independent Central Review (BICR)

  ORR (assessed by BICR per RECIST v1.1) is defined as the proportion of participants with a BOR of confirmed CR or PR. The ORR will be estimated as the number of participants achieving BOR of CR or PR assessed by BICR per RECIST v1.1 divided by the total number of participants.

  From randomization to the end of treatment (Up to 39 months)

• Number of participants with Adverse Events (AEs)

  An AE is any untoward medical occurrence in a patient or clinical study patient, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.

  From first dose to 28 days post last dose

• Number of participants with Serious Adverse Events (SAEs)

  SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in significant disability/incapacity.

  From first dose to 28 days post last dose

Secondary Outcomes (15)

• Overall Response Rate (ORR) per Investigator assessment

  From randomization to the end of treatment (Up to 39 months)

• Overall Survival (OS)

  From randomization to the end of treatment (Up to 39 months)

• Progression-Free Survival (PFS) by BICR

  From randomization to the end of treatment (Up to 39 months)

• Progression-Free Survival (PFS) by Investigator assessment

  From randomization to the end of treatment (Up to 39 months)

• Best overall response (BOR) by BICR

  From randomization to the end of treatment (Up to 39 months)

Study Arms (3)

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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

Arm C SOC (mFOLFOX6+bevacizumab)

ACTIVE COMPARATOR

Drug: Oxaliplatin; Drug: 5-Fluorouracil; Drug: Bevacizumab; Drug: Leucovorin

Interventions

Oxaliplatin DRUG

Specified dose on specified days

Arm A ONO-4578 dose 1 + Opdivo® + SOC (mFOLFOX6 + bevacizumab); Arm B ONO-4578 dose 2 + Opdivo® + SOC (mFOLFOX6 + bevacizumab); Arm C SOC (mFOLFOX6+bevacizumab)

5-Fluorouracil DRUG

Specified dose on specified days

Arm A ONO-4578 dose 1 + Opdivo® + SOC (mFOLFOX6 + bevacizumab); Arm B ONO-4578 dose 2 + Opdivo® + SOC (mFOLFOX6 + bevacizumab); Arm C SOC (mFOLFOX6+bevacizumab)

Bevacizumab DRUG

Specified dose on specified days

Arm A ONO-4578 dose 1 + Opdivo® + SOC (mFOLFOX6 + bevacizumab); Arm B ONO-4578 dose 2 + Opdivo® + SOC (mFOLFOX6 + bevacizumab); Arm C SOC (mFOLFOX6+bevacizumab)

Leucovorin DRUG

Specified dose on specified days

Arm A ONO-4578 dose 1 + Opdivo® + SOC (mFOLFOX6 + bevacizumab); Arm B ONO-4578 dose 2 + Opdivo® + SOC (mFOLFOX6 + bevacizumab); Arm C SOC (mFOLFOX6+bevacizumab)

ONO-4578 DRUG

ONO-4578 tablets once a day

Arm A ONO-4578 dose 1 + Opdivo® + SOC (mFOLFOX6 + bevacizumab); Arm B ONO-4578 dose 2 + Opdivo® + SOC (mFOLFOX6 + bevacizumab)

Opdivo® DRUG

Specified dose on specified days

Also known as: Nivolumab

Arm A ONO-4578 dose 1 + Opdivo® + SOC (mFOLFOX6 + bevacizumab); Arm B ONO-4578 dose 2 + Opdivo® + SOC (mFOLFOX6 + bevacizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ono Pharmaceutical Co. Ltd: lead

Study Sites (28)

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

RECRUITING

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

RECRUITING

Rocky Mountain Cancer Centers, LLP

Lone Tree, Colorado, 80124, United States

RECRUITING

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

RECRUITING

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43221, United States

RECRUITING

Thomas Jefferson University, Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Baylor Scott & White Medical Center

Temple, Texas, 76508, United States

RECRUITING

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

RECRUITING

Blue Ridge Cancer Care

Salem, Virginia, 24153, United States

RECRUITING

Princess Margaret Cancer Centre- University Health Network

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

CHU Besançon - Hôpital Jean Minjoz

Besançon, Doubs, France

RECRUITING

CHU Bordeaux - Hôpital Haut-Lévêque

Pessac, Gironde, France

RECRUITING

Chru De Nantes Hotel-Dieu

Nantes, Loire Atlantique, France

RECRUITING

Hôpital de la Timone

Marseille, Marseille, France

RECRUITING

Hôpital Européen Georges Pompidou

Paris, Paris, France

RECRUITING

Hôpital Saint-Antoine

Paris, Paris, France

RECRUITING

Centre Leon Berard

Lyon, Rhone, France

RECRUITING

CHU Poitiers - Hôpital la Milétrie

Poitiers, Vienne, France

RECRUITING

Istituto Clinico Humanitas

Milan, Italy, Italy

RECRUITING

Istituto Europeo di Oncologia

Milan, Italy, Italy

RECRUITING

Kobe City Medical Center General Hospital

Hyōgo, Kobe-shi, Japan

RECRUITING

National Hospital Organization Osaka National Hospital

Osaka, Osaka-shi, Japan

RECRUITING

Osaka General Medical Center

Osaka, Osaka-shi, Japan

RECRUITING

Osaka International Cancer Institute

Osaka, Osaka-shi, Japan

RECRUITING

Hospital Universitario Reina Sofia

Córdoba, Córdoba, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, Madrid, Spain

RECRUITING

Hospital Universitario Virgen del Rocio

Seville, Sevilla, Spain

RECRUITING

Hospital General Universitario de Valencia

Valencia, Valencia, Spain

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Nivolumab; Oxaliplatin; Fluorouracil; Bevacizumab; Leucovorin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Project Leader

  Ono Pharmaceutical Co. Ltd

  STUDY DIRECTOR

Central Study Contacts

North America Clinical Trial Support Desk

CONTACT

+18665877745(Toll-Free); clinical_trial@ono-pharma.com

International Clinical Trial Support Desk

CONTACT

+17162141777(Standard); clinical_trial@ono-pharma.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2025
• First Posted: April 29, 2025
• Study Start: November 18, 2025
• Primary Completion (Estimated): February 15, 2028
• Study Completion (Estimated): October 1, 2028
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

JP (4); IT (2); ES (4); CA (1); FR (8); US (9)