Clinical trial NCT06948448: 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
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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Colorectal Cancer
Lead sponsor: Ono Pharmaceutical Co. Ltd
Sponsor class: INDUSTRY
First posted: 2025-04-29
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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: 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

Primary outcomes:
measure: Overall Response Rate (ORR) per Blinded Independent Central Review (BICR)
timeFrame: From randomization to the end of treatment (Up to 39 months)
measure: Number of participants with Adverse Events (AEs)
timeFrame: From first dose to 28 days post last dose
measure: Number of participants with Serious Adverse Events (SAEs)
timeFrame: From first dose to 28 days post last dose
Secondary outcomes:
measure: Overall Response Rate (ORR) per Investigator assessment
timeFrame: From randomization to the end of treatment (Up to 39 months)
measure: Overall Survival (OS)
timeFrame: From randomization to the end of treatment (Up to 39 months)
measure: Progression-Free Survival (PFS) by BICR
timeFrame: From randomization to the end of treatment (Up to 39 months)
measure: Progression-Free Survival (PFS) by Investigator assessment
timeFrame: From randomization to the end of treatment (Up to 39 months)
measure: Best overall response (BOR) by BICR
timeFrame: From randomization to the end of treatment (Up to 39 months)
measure: Best overall response (BOR) by Investigator assessment
timeFrame: From randomization to the end of treatment (Up to 39 months)
measure: Duration of response (DOR) by BICR
timeFrame: From randomization to the end of treatment (Up to 39 months)
measure: Duration of response (DOR) by Investigator assessment
timeFrame: From randomization to the end of treatment (Up to 39 months)
measure: Disease Control Rate (DCR) by BICR
timeFrame: From randomization to the end of treatment (Up to 39 months)
measure: Disease Control Rate (DCR) by Investigator assessment
timeFrame: From randomization to the end of treatment (Up to 39 months)
measure: Time to Response (TTR) by BICR
timeFrame: From randomization to the end of treatment (Up to 39 months)
measure: Time to Response (TTR) by Investigator assessment
timeFrame: From randomization to the end of treatment (Up to 39 months)
measure: Maximum percent change in the sum of the diameters of the target lesions by BICR
timeFrame: From randomization to the end of treatment (Up to 39 months)
measure: Maximum percent change in the sum of the diameters of the target lesions by Investigator assessment
timeFrame: From randomization to the end of treatment (Up to 39 months)
measure: Progression-Free Survival of second line therapy (PFS2) by Investigator assessment
timeFrame: From randomization to the end of treatment (Up to 39 months)
Other outcomes:
Locations:
Study officials:
affiliation: Ono Pharma USA Inc
name: Project Leader
role: STUDY_DIRECTOR
References: