The purpose of the study is to determine the safety and tolerability of pembrolizumab/vibostolimab (MK-7684A) in hematological malignancies. This study will also evaluate the overall response rate (ORR), the duration of response (DOR), and disease control rate (DCR) following administration of pembrolizumab/vibostolimab. In addition, this study will characterize pharmacokinetic (PK) profile of vibostolimab (MK-7684).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
192
Pembrolizumab 200 mg + vibostolimab 200 mg/20 mL vial IV infusion Q3W up to approximately 2 years.
Percentage of Participants With a Dose-Limiting Toxicity (DLT)
A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0). Percentage of participants who experience a DLT per CTCAE 5.0 are reported.
Time frame: Up to approximately 6 weeks
Percentage of Participants Who Experienced an Adverse Event (AE)
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. The number of participants who experience an AE are reported.
Time frame: Up to approximately 27 months
Percentage of Participants Who Discontinued Study Treatment Due to an AE
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. The number of participants discontinued from the study treatment due to an AE are reported.
Time frame: Up to approximately 24 months
Objective Response Rate (ORR) as Assessed by Lugano 2014 Classification (Cohorts A-D & F)
ORR for Cohorts A-D and F was assessed based on the Lugano 2014 Classification. ORR is defined as the percentage of the participants who had complete response (CR) or partial response (PR) and was evaluated using computed tomography (CT) and positron emission tomography (PET)-CT. CR is complete metabolic (no/minimal fluorodeoxyglucose \[FDG\] uptake) and radiologic response (target lesions regress to ≤5 cm in longest transverse diameter of a lesion) and no new lesions. PR is partial metabolic (moderate/high FDG uptake) and radiologic response (≥50% decrease in sum of product diameters for multiple lesions of up to 6 target measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by \>50% in length beyond normal). ORR for Cohorts A-D and F is presented. Cohort E is presented separately.
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City of Hope Comprehensive Cancer Center-Hematology ( Site 0024)
Duarte, California, United States
University of Colorado Anschutz Medical Campus-The Center for Cancer and Blood Disorders ( Site 0021
Aurora, Colorado, United States
University of Chicago Medical Center ( Site 0005)
Chicago, Illinois, United States
Henry Ford Hospital ( Site 0003)
Detroit, Michigan, United States
John Theurer Cancer Center at Hackensack University Medical Center ( Site 0004)
Hackensack, New Jersey, United States
Rutgers Cancer Institute of New Jersey ( Site 0023)
New Brunswick, New Jersey, United States
University of Texas MD Anderson Cancer Center ( Site 0014)
Houston, Texas, United States
Medical Oncology Associates, PS ( Site 0001)
Spokane, Washington, United States
MEDICAL COLLEGE OF WISCONSIN ( Site 0016)
Milwaukee, Wisconsin, United States
Instituto do Câncer e Transplante de Curitiba ( Site 0611)
Curitiba, Paraná, Brazil
...and 55 more locations
Time frame: Up to approximately 37 months
ORR as Assessed by the 2016 International Myeloma Working Group (IMWG) Response Criteria (Cohort E)
ORR for Cohort E was measured by 2016 IMWG Response Criteria. ORR is defined as the percentage of the participants with either a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) according to the International Myeloma Working Group (IMWG) Response Criteria. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND \<5% plasmacytomas in the bone marrow; sCR=stringent complete response, CR as above PLUS normal serum free light-chain (FLC) assay ratio and absence of clonal cells in bone marrow; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component \<100 mg/24 hr; PR = ≥50% reduction of serum Mprotein and reduction in 24-hour urinary M-protein by ≥90% or to \<200 mg/24 hours. The ORR for Cohort E is presented. Cohorts A-D and F were presented in a previous outcome measure.
Time frame: Up to approximately 37 months
Duration of Response (DOR) as Assessed by Lugano 2014 Classification (Cohorts A-D & F)
For participants who demonstrate a confirmed complete response (CR) or partial response (PR), DOR is defined as the time from CR or PR to documented disease progression or death. Participants are assessed using computed tomography (CT) and positron emission tomography (PET)- CT and response was evaluated based on the Lugano 2014 Classification (Cheson et al, Journal of Clinical Oncology, 2014). CR is complete metabolic (no/minimal fluorodeoxyglucose \[FDG\] uptake) and radiologic response (target lesions regress to ≤5 cm in longest transverse diameter of a lesion) and no new lesions. PR is partial metabolic (moderate/high FDG uptake) and radiologic response (≥50% decrease in sum of product diameters (SPD) for multiple lesions of up to 6 target measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by \>50% in length beyond normal). DOR for Cohorts A-D and F are presented. Cohort E is presented separately.
Time frame: Up to approximately 37 months
DOR as Assessed by 2016 IMWG Response Criteria (Cohort E)
DOR is defined as the time from CR or PR to documented disease progression or death. DOR for Cohort E was measured by the 2016 IMWG Response Criteria with response criteria defined as participants with either a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR). CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND \<5% plasmacytomas in the bone marrow; sCR=CR as above PLUS normal serum free light-chain (FLC) assay ratio and absence of clonal cells in bone marrow; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component \<100 mg/24 hr; PR = ≥50% reduction of serum Mprotein and reduction in 24-hour urinary M-protein by ≥90% or to \<200 mg/24 hours. The DOR for Cohort E is presented. Cohorts A-D and F were presented in a previous outcome measure.
Time frame: Up to approximately 37 months
Disease Control Rate (DCR) as Assessed by Lugano 2014 Classification (Cohorts A-D & F)
DCR is % of participants who had tumor response per response criteria or have stable disease (SD) for ≥ 12 weeks before any evidence of progressive disease (PD). CR or PR were evaluated with CT and PET-CT. CR: complete metabolic (no/minimal FDG uptake) and radiologic response (target lesions regress to ≤5 cm in longest transverse diameter of a lesion) and no new lesions. PR: partial metabolic (moderate/high FDG uptake) and radiologic response (≥50% decrease in sum of product diameters for multiple lesions of up to 6 target measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by \>50% in length beyond normal). SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. DCR for Cohorts A-D \& F are presented. Cohort E is presented in a separate outcome measure.
Time frame: Up to approximately 37 months
DCR as Assessed by 2016 IMWG Response Criteria (Cohort E)
DCR: percentage of participants who have achieved tumor response or have shown SD for at least 12 weeks before any evidence of PD per IMWG response criteria 2016. Response criteria are defined as participants with either a sCR, CR, VGPR, or PR. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND \<5% plasmacytomas in the bone marrow; sCR=CR as above PLUS normal serum FLC assay ratio and absence of clonal cells in bone marrow; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component \<100 mg/24 hr; PR = ≥50% reduction of serum Mprotein and reduction in 24-hour urinary M-protein by ≥90% or to \<200 mg/24 hours. SD = Not meeting criteria for CR, VGPR, PR, or PD. PD as defined by prespecified 2016 IMWG response criteria. DCR for Cohort E is presented. Cohorts A-D and F were presented in a previous outcome measure.
Time frame: Up to approximately 37 months
Lowest Plasma Concentration (Ctrough) of Vibostolimab
Ctrough is the lowest concentration reached by a drug before the next dose is administered. Blood samples collected predose were used to determine Ctrough of Vibostolimab.
Time frame: Predose at Cycles 1, 3, 7, 11, 15, 19, 23, 27 and 31. Cycle = 3 weeks
Maximum Concentration (Cmax) of Vibostolimab
Cmax is the maximum concentration of the drug observed in plasma. Blood samples collected post dose were used to determine Cmax of Vibostolimab.
Time frame: Postdose: after end of infusion (up to ~10 minutes) at Cycles 1 and 8. Cycle = 3 weeks