Colorectal Neoplasms
Conditions
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
Brief summary
In this study, Chinese participants with MSI-H or dMMR advanced colorectal cancer will be assigned to receive either pembrolizumab or the Investigator's choice of 1 of 6 standard of care (SOC) chemotherapy regimens for treatment. There is no hypothesis testing for this study.
Interventions
BIOLOGICALPembrolizumab
Intravenous (IV) infusion
DRUGOxaliplatin
85 mg/m\^2 given as an intravenous infusion (IV) on Day 1 in each 14-day cycle (Q2W) as part of the mFOLFOX6 regimen
DRUGLeucovorin
400 mg/m\^2 given as an IV on Day 1 Q2W as part of the mFOLFOX6 and FOLFIRI regimens
DRUG5-fluorouracil
400 mg/m\^2 given as an IV bolus on Day 1 and then 1200 mg/m\^2/day IV over 2 days for a total dose of 2400 mg/m\^2 Q2W as part of the mFOLFOX6 and FOLFIRI regimens
DRUGIrinotecan
180 mg/m\^2 IV on Day 1 Q2W as part of the FOLFIRI regimen
BIOLOGICALBevacizumab
IV infusion
BIOLOGICALCetuximab
IV infusion
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The main inclusion and
Exclusion criteria
include but are not limited to the following: Inclusion Criteria: Inclusion Criteria include, but are not limited to: * Has a histologically confirmed diagnosis of colorectal adenocarcinoma that is at stage IV (as defined by American Joint Committee on Cancer eighth edition) \[National Comprehensive Cancer Network 2018\] * Has centrally confirmed Microsatellite Instability-High/Mismatch Repair Deficient (MSI-H/dMMR) status * Has centrally confirmed RAS and BRAF mutation status * A woman of child-bearing potential (WOCBP) must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours for urine or within 72 hours for serum before the first dose of study intervention. * Has measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 as assessed by the local site investigator/radiology * Must provide an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. * Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 3 days before randomization * Has a life expectancy of at least 3 months * Has received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable hepatitis B virus (HBV) viral load prior to randomization if hepatitis B surface antigen (HBsAg) positive * Has an undetectable Hepatitis C Virus (HCV) viral load if HCV infected * Has well controlled Human Immunodeficiency Virus (HIV) on antiretroviral therapy (ART) if HIV infected
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) For All Participants | Up to approximately 77 months | PFS is defined as the time from randomization to the first documented disease progression (PD) per RECIST 1.1 or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more lesions and the unequivocal progression of non-target lesions is also considered PD. The PFS per RECIST 1.1 as assessed by BICR will be reported for all participants. |
| Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) For RAS Wild-type Participants | Up to approximately 77 months | PFS is defined as the time from randomization to the first documented disease progression (PD) per RECIST 1.1 or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more lesions and the unequivocal progression of non-target lesions is also considered PD. The PFS per RECIST 1.1 as assessed by BICR will be reported for RAS wild-type participants . |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) For All Participants | Up to approximately 77 months | OS is defined as the time from randomization to death due to any cause. The OS will be reported for all participants. |
| Overall Survival (OS) For RAS Wild-type Participants | Up to approximately 77 months | OS is defined as the time from randomization to death due to any cause. The OS will be reported for RAS wild-type participants. |
| Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) For All Participants | Up to approximately 77 months | ORR is defined as the percentage of participants who have a best response of confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage for all participants who experience CR or PR as assessed by BICR will be presented. |
| Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) For RAS Wild-type Participants | Up to approximately 77 months | ORR is defined as the percentage of participants who have a best response of confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage for RAS wild-type participants who experience CR or PR as assessed by BICR will be presented. |
| Number of Participants Who Experience at Least One Adverse Event (AE) | Up to approximately 77 months | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experience an AE will be reported. |
| Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) | Up to approximately 77 months | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be reported. |
Countries
China
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed