This trial will evaluate the safety and efficacy of vicriviroc (MK-7690) at 2 dose levels in combination with pembrolizumab (MK-3475) in participants with advanced/metastatic microsatellite stable (MSS) colorectal cancer (CRC).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
41
Vicriviroc tablets administered orally, QD at dose level 1 or 2.
Pembrolizumab administered by IV infusion at 200 mg every 3 weeks (Q3W), given on cycle day 1.
Honor Health ( Site 0103)
Scottsdale, Arizona, United States
California Cancer Associates for Research & Excellence ( Site 0100)
Encinitas, California, United States
California Cancer Associates for Research & Excellence ( Site 0102)
Fresno, California, United States
Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1)
Objective response rate (ORR) was defined as the percentage of 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 Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by the investigator. ORR was estimated and analyzed using Clopper-Pearson interval.
Time frame: Up to ~32 months
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
DLTs were assessed during the first cycle (21 days) \& were defined as: Grade (Gr) 4 nonhematologic toxicity; Gr 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia, Gr 4 thrombocytopenia of any duration, Gr 3 thrombocytopenia associated with bleeding; nonhematologic adverse event (AE) ≥ Gr 3 (with exceptions); Gr 3 or 4 nonhematologic lab abnormality (if medical intervention was required, lead to hospitalization, or persisted for \>72 hours); Gr 3 or 4 febrile neutropenia; inability to receive ≥75% of the planned vicriviroc dose because of drug-related tolerability; drug-related toxicity that caused a \>2 week delay in Cycle 2 initiation; elevated aspartate aminotransferase or alanine aminotransferase lab value that is \>3× upper limit of normal (ULN) \& an elevated total bilirubin value \>2× ULN \& an alkaline phosphatase value \<2× ULN, in which no alternative reasons were found.
Time frame: Up to Day 21 of Cycle 1 (each cycle is 21 days)
Number of Participants Who Experienced an Adverse Event (AE)
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 with at least one AE was assessed.
Time frame: Up to ~28 months
Number of Participants Who Discontinued Study Treatment Due to an AE
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Florida Cancer Specialists (South Region) - Research Office ( Site 7001)
Fort Myers, Florida, United States
Tennessee Oncology, PLLC/The Sarah Cannon Research Institute ( Site 7000)
Nashville, Tennessee, United States
Baylor Scott & White Medical Center - Temple ( Site 0104)
Temple, Texas, United States
Cross Cancer Institute ( Site 0201)
Edmonton, Alberta, Canada
CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0204)
Montreal, Quebec, Canada
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 discontinued treatment due to an AE was assessed
Time frame: Up to ~25 months
Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria in Solid Tumors 1.1 for Immune-based Therapeutics (iRECIST)
An objective response rate was defined as the percentage of participants who experienced an immune-based complete response (iCR: disappearance of all target lesions) or immune-based partial response (iPR: at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experienced an iCR or iPR using immune-based therapeutics Response Evaluation Criteria in Solid Tumors (iRECIST) per investigator was presented. ORR was estimated and analyzed using Clopper-Pearson interval.
Time frame: Up to ~32 months
Progression-Free Survival (PFS) Based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1)
PFS was defined as the time from the first dose of study treatment to the date of the first documentation of disease progression, as determined by investigator per RECIST 1.1 or death due to any cause (whichever occurred first). Disease progression was defined as at least 20 percent (%) increase (including an absolute increase of at least 5 millimeter \[mm\]) in the sum of diameter of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method.
Time frame: Up to ~32 months
PFS Based on Modified Response Evaluation Criteria in Solid Tumors 1.1 for Immune-based Therapeutics (iRECIST)
PFS was defined as the time from the first dose of study treatment to the date of the first documentation of disease progression, as determined by investigator per modified iRECIST or death due to any cause (whichever occurred first). Disease progression was defined as at least 20 percent (%) increase (including an absolute increase of at least 5 millimeter \[mm\]) in the sum of diameter of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method.
Time frame: Up to ~32 months
Overall Survival (OS)
OS is defined as the time from the first dose of study treatment until death from any cause.
Time frame: Up to ~32 months
Plasma Area Under the Concentration Time-Curve From 0 to 8 Hours (AUC 0-8hrs) of Vicriviroc
Plasma vicriviroc concentration was quantified for each arm to determine AUC 0-8hrs, defined as the area under the concentration vs. time curve for vicriviroc from 0 to 8 hours.
Time frame: Pre-dose, 1, 2, 4, and 8 hours after vicriviroc administration on Cycle 1 (each cycle= 21-days) Day 1, Cycle 2 Day 1.
Maximum Observed Plasma Concentration (Cmax) of Vicriviroc
Plasma vicriviroc concentration was quantified for each arm to determine Cmax, defined as the maximum observed concentration of vicriviroc in plasma.
Time frame: Pre-dose, 1, 2, 4, and 8 hours after vicriviroc administration on Cycle 1 (each cycle= 21-days) Day 1, Cycle 2 Day 1.
Trough Plasma Concentration (Ctrough) of Vicriviroc
Plasma vicriviroc concentration was quantified for each arm to determine Ctrough, defined as the minimum plasma concentration of vicriviroc observed after administration and just before the subsequent dose.
Time frame: Pre-dose, and 1, 2, 4, and 8 hours after vicriviroc administration on Cycle 1 (each cycle= 21-days) Day 1; Cycle 3 Day 21.