A Study of Pembrolizumab/Vibostolimab (MK-7684A) in Relapsed/Refractory Hematological Malignancies (MK-7684A-004, KEYVIBE-004)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Cmax is the maximum concentration of the drug observed in plasma. Blood samples collected post dose were used to determine Cmax of Vibostolimab.