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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 · Ono Pharmaceutical Co., Ltd.
In plain English
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Official title
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
About this study
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
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
Study design
Enrollment target: 144 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2025-11-18
Estimated completion: 2028-10-01
Last updated: 2026-03-27
Interventions
Drug: ONO-4578Drug: Opdivo®Drug: OxaliplatinDrug: 5-FluorouracilDrug: BevacizumabDrug: Leucovorin
Primary outcomes
- • Overall Response Rate (ORR) per Blinded Independent Central Review (BICR) (From randomization to the end of treatment (Up to 39 months))
- • Number of participants with Adverse Events (AEs) (From first dose to 28 days post last dose)
- • Number of participants with Serious Adverse Events (SAEs) (From first dose to 28 days post last dose)
Sponsor
Ono Pharmaceutical Co., Ltd. · industry
Contacts & investigators
ContactNorth America Clinical Trial Support Desk · contact · clinical_trial@ono-pharma.com · +18665877745(Toll-Free)
ContactInternational Clinical Trial Support Desk · contact · clinical_trial@ono-pharma.com · +17162141777(Standard)
InvestigatorProject Leader · study_director, Ono Pharmaceutical Co., Ltd.
All locations (28)
Mayo Clinic ArizonaRecruiting
Phoenix, Arizona, United States
USC Norris Comprehensive Cancer CenterRecruiting
Los Angeles, California, United States
Rocky Mountain Cancer Centers, LLPRecruiting
Lone Tree, Colorado, United States
Mayo Clinic FloridaRecruiting
Jacksonville, Florida, United States
The Ohio State University Comprehensive Cancer CenterRecruiting
Columbus, Ohio, United States
Thomas Jefferson University, Sidney Kimmel Cancer CenterRecruiting
Philadelphia, Pennsylvania, United States
Baylor Scott & White Medical CenterRecruiting
Temple, Texas, United States
Virginia Oncology AssociatesRecruiting
Norfolk, Virginia, United States
Blue Ridge Cancer CareRecruiting
Salem, Virginia, United States
Princess Margaret Cancer Centre- University Health NetworkRecruiting
Toronto, Ontario, Canada
CHU Besançon - Hôpital Jean MinjozRecruiting
Besançon, Doubs, France
CHU Bordeaux - Hôpital Haut-LévêqueRecruiting
Pessac, Gironde, France
Chru De Nantes Hotel-DieuRecruiting
Nantes, Loire Atlantique, France
Hôpital de la TimoneRecruiting
Marseille, Marseille, France
Hôpital Européen Georges PompidouRecruiting
Paris, Paris, France
Hôpital Saint-AntoineRecruiting
Paris, Paris, France
Centre Leon BerardRecruiting
Lyon, Rhone, France
CHU Poitiers - Hôpital la MilétrieRecruiting
Poitiers, Vienne, France
Istituto Clinico HumanitasRecruiting
Milan, Italy, Italy
Istituto Europeo di OncologiaRecruiting
Milan, Italy, Italy
Kobe City Medical Center General HospitalRecruiting
Hyōgo, Kobe-shi, Japan
National Hospital Organization Osaka National HospitalRecruiting
Osaka, Osaka-shi, Japan
Osaka General Medical CenterRecruiting
Osaka, Osaka-shi, Japan
Osaka International Cancer InstituteRecruiting
Osaka, Osaka-shi, Japan
Hospital Universitario Reina SofiaRecruiting
Córdoba, Córdoba, Spain
Hospital Universitario 12 de OctubreRecruiting
Madrid, Madrid, Spain
Hospital Universitario Virgen del RocioRecruiting
Seville, Sevilla, Spain
Hospital General Universitario de ValenciaRecruiting
Valencia, Valencia, Spain