The purposes of this study are to determine the safety and tolerability of MK-7162 when administered in combination with pembrolizumab (MK-3475) and to establish a preliminary recommended Phase 2 dose (RP2D) of MK-7162 when administered in combination with pembrolizumab.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
33
oral tablets
IV infusion
UCLA Medical Center ( Site 0002)
Santa Monica, California, United States
START Midwest ( Site 0007)
Grand Rapids, Michigan, United States
Laura and Isaac Perlmutter Cancer Center ( Site 0001)
New York, New York, United States
Princess Margaret Hospital.. ( Site 0130)
Toronto, Ontario, Canada
Number of Participants Experiencing Dose-limiting Toxicities (DLTs) as Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 by the Investigator
The following events, if considered drug related by the investigator, are considered a DLT: Grade 4 nonhematologic toxicity; Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia; Grade 4 thrombocytopenia of any duration; Grade 3 thrombocytopenia associated with bleeding; Nonhematologic Adverse Events (AE) ≥Grade 3 with exceptions; Grade 3 or Grade 4 non-hematologic laboratory values if requires medical intervention, leads to hospitalization, persists for \>1 week, or results in a Drug-induced Liver Injury with exceptions; Grade 3 of 4 febrile neutropenia; Treatment-related toxicities that lead to discontinuation of study treatment during Cycles 1 or 2; Prolonged delay (\>2 weeks) in initiating Cycles 2 or 3 due to treatment-related toxicity; Missing \>25% of MK-7162 doses as a result of treatment-related AE during Cycles 1 or 2; Grade 5 toxicity.
Time frame: Cycle 1 and Cycle 2 (Up to 6 weeks)
Number of Participants Who Experienced an Adverse Event (AE)
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. 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 treatment.
Time frame: Up to Approximately 27 Months
Number of Participants Who Discontinued Study Drug Due to an 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.
Time frame: Up to Approximately 26 Months
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Chaim Sheba Medical Center. ( Site 0301)
Ramat Gan, Israel
Severance Hospital Yonsei University Health System ( Site 0103)
Seoul, South Korea
Area Under the Concentration-Time Curve (AUC) From 0-8 Hours of MK-7261 Alone and in Combination With Pembrolizumab
Blood samples were collected at designated time points for determining the AUC₀-₈ of MK-7162 in plasma when administered alone and in combination with pembrolizumab.
Time frame: Pre-dose and at 1, 2, 4, and 8 hours post-dose on Cycle 1, Days 1 & 15; and Cycle 3, Day 1
Minimum Plasma Concentration (Cmin) of MK-7162
Blood samples were obtained at designated time points to determine the Cmin of MK-7162 in plasma.
Time frame: Pre-dose and at 1, 2, 4, and 8 hours post-dose on Cycle 1, Day 14
Maximum Plasma Concentration (Cmax) of MK-7162 When Administered Alone and in Combination With Pembrolizumab
Blood samples were collected at designated time points to determine the Cmax of MK-7162 in plasma when administered alone and in combination with pembrolizumab.
Time frame: Pre-dose and at 1, 2, 4, and 8 hours post-dose on Cycle 1, Days 1 and 15 and Cycle 3, Day 1
Kynurenine (KYN) Biomarker Plasma Concentration
MK-7162 is a selective inhibitor of Indoleamine-2,3-dioxygenase-1 (IDO1) activity which, in turn, reduces the conversion of TRP to KYN. Venous blood samples were collected after an overnight fast for measurement of plasma levels of KYN as a pharmacodynamic biomarker of IDO1 inhibition.
Time frame: Cycle 1 Days 1 & 15: predose, 1, 2, 4 & 8 hours postdose; Cycle 2 Day 1: predose; Cycle 3 Day 1: predose, 1, 2, 4 & 8 hours postdose; Cycle 3 Day 15: predose
Tryptophan (TRP) Biomarker Plasma Concentration
MK-7162 is a selective inhibitor of Indoleamine-2,3-dioxygenase-1 (IDO1) activity which, in turn, reduces the conversion of TRP to KYN. Venous blood samples were collected at designated time points after an overnight fast for measurement of plasma levels of TRP as a pharmacodynamic biomarker of IDO1 inhibition.
Time frame: Cycle 1 Days 1 & 15: predose, 1, 2, 4 & 8 hours postdose; Cycle 2 Day 1: predose; Cycle 3 Day 1: predose, 1, 2, 4 & 8 hours postdose; Cycle 3 Day 15: predose
Objective Response Rate (ORR) Based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator
ORR is defined as the percentage of participants in the analysis population who have 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, taking as reference the baseline sum diameters) per RECIST 1.1 as assessed by the Investigator. The percentage of participants who experience a CR or PR based on RECIST 1.1 will be presented.
Time frame: Up to approximately 28 months
Overall Response Based on Immune Response Evaluation Criteria (iRECIST) In Solid Tumors
Participants with PD by RECIST 1.1 as determined by investigator underwent confirmatory imaging to classify the disease as confirmed progressive disease (iCPD), unconfirmed progressive disease \[iUPD\]), stable disease (iSD), partial response (iPR) or complete response (iCR). iCPD definition: Worsening of target lesions (increase in the sum of diameters of ≥5 mm); Any significant growth in non-target lesions, Appearance of new lesions, increase in new lesion sum of diameters by ≥5 mm; Visible growth of new non-target lesions; or appearance of new factor that would have triggered PD by RECIST 1.1. Responses are classified as iSD or iPR (depending on the sum of diameters of the target lesions), or iCR if all lesions resolve. iUPD overall response is defined as none of the progression-confirming factors identified in iCPD occurs AND The target lesion sum of diameters (initial target lesions) remains above the initial PD threshold (by RECIST 1.1)
Time frame: Up to approximately 28 months