In this study, participants with stage IV Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) colorectal carcinoma (CRC) will be randomly assigned to receive either pembrolizumab or the Investigator's choice of 1 of 6 standard of care (SOC) chemotherapy regimens for the treatment of advanced colorectal carcinoma. The primary study hypothesis is that pembrolizumab will prolong progression-free survival (PFS) or overall survival (OS) compared to current SOC chemotherapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
307
Regimen consists of oxaliplatin 85 mg/m\^2 IV on Day 1, leucovorin 400 mg/m\^2 or levoleucovorin 200 mg/m\^2 IV on Day 1, 5-fluorouracil (5-FU) 400 mg/m\^2 IV bolus on Day 1 and then 1200 mg/m\^2/day IV over 2 days for total dose of 2400 mg/m\^2 in each 2-week cycle
Regimen consists of irinotecan 180 mg/m\^2 IV on Day 1, leucovorin 400 mg/m\^2 or levoleucovorin 200 mg/m\^2 IV on Day 1, 5-FU 400 mg/m\^2 IV bolus on Day 1 and then 1200 mg/m\^2/day IV over 2 days for total dose of 2400 mg/m\^2 in each 2-week cycle
IV infusion
IV infusion
IV infusion
Progression-Free Survival (PFS) Per RECIST1.1 As Assessed by Central Imaging Vendor
PFS was defined as the time from randomization to the first documented disease progression (PD) per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Hazards ratio (HR) and associated 95% confidence intervals (CIs) from a Cox proportional hazard model with Efron's method of tie handling and with a single treatment covariate was presented for the first course study treatment per protocol.
Time frame: Up to approximately 59 months
Overall Survival (OS)
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of analysis were censored at the date of last known contact. HR and associated 95% CIs from a Cox proportional hazard model with Efron's method of tie handling and with a single treatment covariate was presented for the first course study treatment per protocol.
Time frame: Up to approximately 59 months
Overall Response Rate (ORR) Per RECIST1.1 as Assessed by Central Imaging Vendor
ORR was defined as the percentage of the participants who experienced a Complete Response (CR; disappearance of all target lesions) or a Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 as assessed by the central imaging vendor. The percentage of participants who experienced a CR or PR was presented for the first course of study treatment per protocol.
Time frame: Up to approximately 59 months
Number of Participants Who Experienced an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change infrequency and/or intensity) of a preexisting condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE was presented for the first course study treatment per protocol.
Time frame: Up to approximately 59 months
Number of Participants Who Discontinued Study Treatment Due to an AE
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change infrequency and/or intensity) of a preexisting condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE was presented for the first course study treatment per protocol.
Time frame: Up to approximately 59 months
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