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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ono Pharmaceutical Co. Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

25 Nov 2025 → ongoing

Decision date (initial)

2025-09-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Ono Pharmaceutical Co. Ltd.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Therapy, Pharmacokinetic, Efficacy, Safety, Others

1. To evaluate the safety and tolerability of two dose levels of ONO-4578 with Opdivo plus standard of care (SOC)
2. To evaluate the efficacy of two dose levels of ONO-4578 with Opdivo plus standard of care compared to SOC

Secondary objectives 2

1. To investigate two dose levels of ONO-4578 in combination with Opdivo plus standard of care with respect to safety procedures and laboratory tests
2. To investigate two doses of ONO-4578 in combination with Opdivo plus standard of care with respect to efficacy endpoints compared to SOC

Conditions and MedDRA coding

PD-L1 positive advanced colorectal cancer

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. - Participant must be ≥18 years at the time of signing informed consent. - Able and willing to give informed consent. - Willing to participate and comply with the requirements of the entire trial.
2. - Histologically confirmed advanced (locally advanced or metastatic) colorectal cancer not amenable to curative resection. - ECOG Performance Status of 0-1. - Available local test results for microsatellite stability or mismatch repair (MMR) status. - Available local test results for tumor BRAF mutation status. - No prior systemic treatment for advanced local or metastatic colorectal cancer (mCRC). - Presence of at least one measurable lesion as defined by RECIST v1.1 on diagnostic imaging assessed per local Investigator within 28 days prior to randomization.
3. - Adequate newly obtained or archival tumor tissue not previously irradiated is available for assessment of PD-L1 status by central laboratory. - Participants whose tumor is positive for PD-L1 expression (defined as Combined Positive Score (CPS) ≥ 1) as determined at a central laboratory.
4. - Participants with adequate bone marrow, renal, and hepatic function as defined in the protocol.
5. - Female and male participants who agrees to use a highly effective contraceptive method as defined in the protocol.

Exclusion criteria 5

1. - Participants with high microsatellite instability (MSI-High), or mismatch repair deficient (dMMR) tumor. - Participants with BRAF V600E mutation. - Active brain metastases or leptomeningeal metastases.
2. - Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured and considered to be of low risk of recurrence. - Prior bone marrow or solid organ transplant.
3. - Gastrointestinal, Respiratory and Cardiovascular conditions as defined in the protocol.
4. - Gastrointestinal, Respiratory and Cardiovascular conditions as defined in the protocol. - History of medical conditions with treatments used in the study, as defined in the protocol. - Other medical conditions as defined in the protocol.
5. - Other exclusion criteria as defined in the protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. - Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) - Dose interruptions, dose reductions, and drug discontinuations due to treatment-emergent AEs
2. Overall response rate (ORR) by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Secondary endpoints 4

1. - Changes in physical examination findings - Changes in laboratory parameters (hematology, clinical chemistry, coagulation, and urinalysis) - Changes in 12-lead electrocardiogram (ECG) findings
2. - ORR site Investigator assessment per RECIST v1.1 - Overall survival (OS) - Progression-free survival (PFS) by BICR and site Investigator assessment per RECIST v1.1 - Best overall response (BOR) by BICR and site Investigator assessment per RECIST v1.1 - Duration of response (DOR) by BICR and site Investigator assessment per RECIST v1.1
3. - Disease control rate (DCR) by BICR and site Investigator assessment per RECIST v1.1 - Time to response (TTR) by BICR and site Investigator assessment per RECIST v1.1 - Maximum percent change in the sum of the diameters of the target lesions by BICR and site Investigator assessment per RECIST v1.1
4. - Progression-free survival of second line therapy (PFS2) by site Investigator assessment per RECIST v1.1

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Comparator 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ono Pharmaceutical Co. Ltd.

Sponsor organisation

Ono Pharmaceutical Co. Ltd.

Address

1-8-2 Kyutaromachi, Chuo Chuo

City

Osaka

Postcode

541-8564

Country

Japan

Scientific contact point

Organisation

Ono Pharmaceutical Co. Ltd.

Contact name

Project Leader, Study Director

Public contact point

Organisation

Ono Pharmaceutical Co. Ltd.

Contact name

Project Leader, Study Director

Third parties 10

Locations

3 EU/EEA countries · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 46 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications