The purpose of this study is to assess the efficacy and safety and establish a preliminary recommended Phase 2 dose (RP2D) of MK-6598 administered as monotherapy and in combination with pembrolizumab (MK-3475) in adult participants with advanced or metastatic solid tumors.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
39
Oral tablet
Intravenous (IV) infusion
Sanford Cancer Center ( Site 0300)
Sioux Falls, South Dakota, United States
Princess Margaret Cancer Centre ( Site 0101)
Toronto, Ontario, Canada
Centre Hospitalier de l'Université de Montréal-Unit for Innovative Therapies ( Site 0100)
Montreal, Quebec, Canada
Hôpitaux Universitaires de Genève (HUG) ( Site 0202)
Geneva, Canton of Geneva, Switzerland
Number of Participants With a Dose-Limiting Toxicity (DLT) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events (AEs) Version 5.0
DLT is defined as any of the following toxicities, unless assessed by investigator as due to the underlying disease or extraneous causes: Grade (Gr) 4 nonhematologic toxicity (not laboratory); Gr 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia; Gr 4 thrombocytopenia of any duration; Gr 3 thrombocytopenia associated with clinically significant bleeding lasting ≥7 days; Gr 4 anemia of any duration; Nonhematologic AE Gr ≥3 in severity, with exceptions; Any Gr 3/4 nonhematologic lab abnormality if it requires clinically significant medical intervention, leads to hospitalization, persists for \>72 hours, or results in certain drug-induced liver injuries, with some exceptions; Gr 3 or 4 febrile neutropenia; \>2 week delay in initiating Cycle 2 due to treatment-related toxicity; Treatment-related toxicity resulting in study treatment discontinuation during Cycle 1 (C1), 1 cycle = 21 days; Missing \>25% of MK-6598 doses due to treatment-related AE during C1; Gr 5 toxicity.
Time frame: Up to approximately 21 days
Number of Participants Who Experienced At Least One 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 who experienced an AE will be reported.
Time frame: Up to approximately 24 months
Number of Participants Who Discontinue Study Treatment 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. The number of participants who discontinued study treatment due to an AE will be reported.
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Ospedale Regionale Bellinzona e Valli ( Site 0200)
Bellinzona, Canton Ticino, Switzerland
Cantonal Hospital St.Gallen ( Site 0203)
Sankt Gallen, Switzerland
Time frame: Up to approximately 24 months
Area Under the Curve From Time 0 to Last Quantifiable Sample (AUC0-last) of MK-6598
Blood samples were collected at pre-specified time points to determine the AUC0-last of MK-6598 in participant's plasma. AUC0-last of MK-6598 was defined as the area under the concentration-time curve from time 0 to the time of the last quantifiable (above lower limit of quantitation) concentration. AUC0-last was calculated using noncompartmental analysis. Geometric coefficient of variation is calculated in the natural log-scale with the equation:100 x sqrt(exp(σ\^2) - 1), where σ\^2 is the observed variance on the natural log scale.
Time frame: Days 1, 8, and 15 of Cycle 1: predose, postdose at 30 minutes (min), 45 min, 60 min, 2 hours (hrs), 6 hrs. Days 2 and 9 of Cycle 1: predose.
Minimum Serum Concentration (Cmin) of MK-6598
Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmin. Geometric coefficient of variation is calculated in the natural log-scale with the equation:100 x sqrt(exp(σ\^2) - 1), where σ\^2 is the observed variance on the natural log scale.
Time frame: Days 8 and 15 of Cycle 1: predose, postdose at 30 min, 45 min, 60 min, 2 hrs, 6 hrs. Days 2 and 9 of Cycle 1: predose.
Maximum Serum Concentration (Cmax) of MK-6598
Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmax. Geometric coefficient of variation is calculated in the natural log-scale with the equation:100 x sqrt(exp(σ\^2) - 1), where σ\^2 is the observed variance on the natural log scale.
Time frame: Days 1, 8, and 15 of Cycle 1: predose, postdose at 30 min, 45 min, 60 min, 2 hrs, 6 hrs. Days 2 and 9 of Cycle 1: predose.
Tumor Phenylpyruvate Concentration
Tumor core biopsy sample collected during screening period and cycle 2 (21 day cycles) day 1 to determine tumor phenylpyruvate concentration (pmol/mg).
Time frame: Approximately Day 22
Time to Maximum Concentration (Tmax) of MK-6598
Tmax was defined as the time to maximum concentration of MK-6598 observed in plasma. Blood samples were collected pre-dose and post-dose at designated timepoints to determine Tmax of MK-6598.
Time frame: Days 1, 8, and 15 of Cycle 1: predose, postdose at 30 min, 45 min, 60 min, 2 hrs, 6 hrs. Days 2 and 9 of Cycle 1: predose.