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
90
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 the investigator to be clearly 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; Gr 4 anemia regardless of duration; Nonhematologic AE Gr ≥3 in severity, with exceptions; Any Gr 3 or 4 nonhematologic lab abnormality if clinically significant medical intervention is required, or if leads to hospitalization, persists for \>72 hours or results in drug-induced liver injury with exceptions; Gr 3 or 4 febrile neutropenia; Prolonged delay (\>2 weeks) in initiating Cycle 2 due to treatment-related toxicity; Treatment-related toxicity resulting in study treatment discontinuation during Cycle 1 (C1); Missing \>25% of MK-6598 doses as a result of treatment-related AE during C1; Gr 5 toxicity.
Time frame: Up to approximately 21 days
Number of Participants Who Experience 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 27 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 (AUC) of MK-6598
Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine AUC.
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; Day 1 of Cycles 2, 5, 10, 15, 20, 25, 30, and 35: 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
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; Day 1 of Cycles 2, 5, 10, 15, 20, 25, 30, and 35: 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.
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; Day 1 of Cycles 2, 5, 10, 15, 20, 25, 30, and 35: predose
Tumor Phenylpyruvate Concentrations
Blood samples pre-dose and at multiple timepoints post-dose will be used to determine tumor phenylpyruvate concentrations.
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; Day 1 of Cycles 2, 5, 10, 15, 20, 25, 30, and 35: predose