4-[4-CYANO-2-[[(1'R,4S)-6-(PROPAN-2-YLCARBAMOYL)SPIRO[2,3-DIHYDROCHROMENE-4,2'-CYCLOPROPANE]-1'-CARBONYL]AMINO]PHENYL]BUTANOIC ACID for Advanced colorectal cancer (non‑MSI‑H/dMMR, PD‑L1 positive)

Inclusion criteria

• {"criterion_text":"- Participant must be ≥18 years at the time of signing informed consent.\n- Able and willing to give informed consent.\n- Willing to participate and comply with the requirements of the entire trial.\n- Histologically confirmed advanced (locally advanced or metastatic) colorectal cancer not amenable to curative resection.\n- ECOG Performance Status of 0-1.\n- Available local test results for microsatellite stability or mismatch repair (MMR) status.\n- Available local test results for tumor BRAF mutation status.\n- No prior systemic treatment for advanced local or metastatic colorectal cancer (mCRC).\n- 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.\n- Adequate newly obtained or archival tumor tissue not previously irradiated is available for assessment of PD-L1 status by central laboratory.\n- Participants whose tumor is positive for PD-L1 expression (defined as Combined Positive Score (CPS) ≥ 1) as determined at a central laboratory.\n- Participants with adequate bone marrow, renal, and hepatic function as defined in the protocol.\n- Female and male participants who agrees to use a highly effective contraceptive method as defined in the protocol."}

Exclusion criteria

• {"criterion_text":"- Participants with high microsatellite instability (MSI-High), or mismatch repair deficient (dMMR) tumor.\n- Participants with BRAF V600E mutation.\n- Active brain metastases or leptomeningeal metastases.\n- 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.\n- Prior bone marrow or solid organ transplant.\n- Gastrointestinal, Respiratory and Cardiovascular conditions as defined in the protocol.\n- Gastrointestinal, Respiratory and Cardiovascular conditions as defined in the protocol.\n- History of medical conditions with treatments used in the study, as defined in the protocol.\n- Other medical conditions as defined in the protocol.\n- Other exclusion criteria as defined in the protocol."}

Primary endpoints

• {"endpoint_text":"- Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) - Dose interruptions, dose reductions, and drug discontinuations due to treatment-emergent AEs","definition_or_measurement_approach":"Safety endpoints measured as incidence and severity of AEs and SAEs; includes measurement of dose interruptions, dose reductions, and drug discontinuations due to treatment-emergent AEs (as reported in safety assessments)."}
• {"endpoint_text":"- Overall response rate (ORR) by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1","definition_or_measurement_approach":"Efficacy measured as ORR assessed by Blinded Independent Central Review per RECIST v1.1."}

Secondary endpoints

• {"endpoint_text":"- Changes in physical examination findings - Changes in laboratory parameters (hematology, clinical chemistry, coagulation, and urinalysis) - Changes in 12-lead electrocardiogram (ECG) findings","definition_or_measurement_approach":"Safety and tolerability measures including changes from baseline in physical exam findings, laboratory parameters (hematology, clinical chemistry, coagulation, urinalysis), and 12-lead ECG findings."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Efficacy endpoints including ORR by site investigator (RECIST v1.1), overall survival, PFS by BICR and investigator (RECIST v1.1), BOR by BICR and investigator, and DOR by BICR and investigator."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Tumor-response related endpoints assessed by BICR and investigator per RECIST v1.1: DCR, TTR, and maximum % change in sum of diameters of target lesions."}
• {"endpoint_text":"- Progression-free survival of second line therapy (PFS2) by site Investigator assessment per RECIST v1.1","definition_or_measurement_approach":"PFS2 assessed by site investigator per RECIST v1.1 (time-to-event measurement for second-line therapy progression-free survival)."}

France

Earliest CTIS Part Ii Submission Date

27-06-2025

Latest Decision Or Authorization Date

18-02-2026

Processing Time Days

236

Number Of Sites

9

Number Of Participants

28

Italy

Earliest CTIS Part Ii Submission Date

04-08-2025

Latest Decision Or Authorization Date

23-02-2026

Processing Time Days

203

Number Of Sites

6

Number Of Participants

24

Spain

Earliest CTIS Part Ii Submission Date

17-07-2025

Latest Decision Or Authorization Date

20-02-2026

Processing Time Days

218

Number Of Sites

7

Number Of Participants

24

Primary sponsor

Full Name

Ono Pharmaceutical Co. Ltd.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Japan

Contract research organisations

Name

IQVIA Limited

Responsibilities

Multiple study support functions (codes 1,2,3,5-15; eCOA (QOLs and eDiary), Cenduit (IRT))

Name

PPD Development LP

Responsibilities

code 4

Name

Bioclinica Inc.

Responsibilities

code 15 (Imaging Services)

Name

Labcorp Central Laboratory Services LP

Responsibilities

code 4

Name

Labcorp Central Laboratory Services SARL

Responsibilities

code 4

Name

Cmic Inc.

Responsibilities

code 4

Third parties

• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"code 15 (Imaging Services)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"codes 1,12,13,14,15 (eCOA (QOLs and eDiary), Cenduit (IRT)),2,3,5,6,7,8,9","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"code 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Cmic Inc.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Catalent Germany Schorndorf GmbH","duties_or_roles":"code 14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Agilent Technologies, Inc.","duties_or_roles":"code 15 (IVDR (PD-L1))","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"code 15 (Global Patient Travel and Reimbursement)","organisation_type":"Non-Pharmaceutical company"}