In Cycle 1, participants received MK-8242 60 mg administered orally (PO) twice a day (BID) on Days 1-6 and PO once daily (QD) in the morning on Day 7 of the 21-day cycle to accommodate pharmacokinetic (PK) sampling. In Cycle 2 and subsequent cycles, participants received MK-8242 60 mg PO BID on Days 1-7 of each 21-day cycle.

In Cycle 1, participants received MK-8242 120 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling. In Cycle 2 and subsequent cycles, participants received MK-8242 120 mg PO BID on Days 1-7 of each 21-day cycle.

In Cycle 1, participants received MK-8242 170 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling. In Cycle 2 and subsequent cycles, participants received MK-8242 170 mg PO BID on Days 1-7 of each 21-day cycle.

In Cycle 1, participants received MK-8242 250 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling. In Cycle 2 and subsequent cycles, participants received MK-8242 250 mg PO BID on Days 1-7 of each 21-day cycle.

In Cycle 1, participants received MK-8242 300 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling. In Cycle 2 and subsequent cycles, participants received MK-8242 300 mg PO BID on Days 1-7 of each 21-day cycle.

In Cycle 1, participants received MK-8242 350 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling. In Cycle 2 and subsequent cycles, participants received MK-8242 350 mg PO BID on Days 1-7 of each 21-day cycle.

In Cycle 1, participants received MK-8242 400 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling. In Cycle 2 and subsequent cycles, participants received MK-8242 400 mg PO BID on Days 1-7 of each 21-day cycle.

In Cycle 1, participants received MK-8242 500 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling. In Cycle 2 and subsequent cycles, participants received MK-8242 500 mg PO BID on Days 1-7 of each 21-day cycle.

MK-8242

Medical Director

This study is being done to evaluate the safety and pharmacokinetic profile of MK-8242 and its active metabolite (M16) in participants with advanced solid tumors. In Part 1 of the study, the study drug dose will be escalated to determine the maximum tolerated dose (MTD). In Part 2 of the study, the MTD will be confirmed and the recommended Phase 2 dose (RPTD) established; the effect of MK-8242 on liposarcoma and other tumor types will also be evaluated.

Participants are considered to have completed the study after Cycle 12. Amendment 4 (14 April 2015) was done to allow participants on active treatment at the time the study was closed to enrollment to continue study treatment beyond Cycle 12 if deriving clinical benefit, at the Investigator's discretion.

Study of Safety and Pharmacokinetics of MK-8242 in Participants With Advanced Solid Tumors (P07650)

A Phase I Study to Evaluate the Safety and Tolerability and Pharmacokinetic/Pharmacodynamics of MK-8242 in Patients With Advanced Solid Tumors

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

DLT was defined as: any drug-related hematologic toxicity ≥ Grade 3 lasting ≥1 week, ≥ Grade 3 thrombocytopenia with bleeding, ≥ Grade 3 neutropenia with infection OR non-hematologic DLTs that were any Grade 3, 4, or 5 toxicity with the following exceptions/clarifications: 1) Grade 3 nausea, vomiting, diarrhea, and dehydration were excluded from the determination of DLT if, in the opinion of the investigator and sponsor, they occurred in a setting of inadequate treatment, 2) Grade 3 nausea, vomiting, diarrhea, and dehydration were each considered a DLT if they persisted despite 72 hours of maximal supportive care measures or 3) Any abnormal non-hematological laboratory value ≥ Grade 3 (that is not attributable to any other causes) was considered a DLT only if medical intervention was required to treat the participant, the abnormality led to hospitalization, or the abnormality persisted for ≥1 week.

PK plasma samples were to be collected at the following time points: 0, 0.5, 1, 2, 4, 6, 8,and 12 hours after the first dose on Day 1; and 0, 0.5, 1, 2, 4, 6, 8, 12, 24 (Day 8) and 48 (Day 9) hours post-dose on Day 7.

PK plasma samples were to be collected at the following time points: 0, 0.5, 1, 2, 4, 6, 8 and 12 hours after the first dose on Day 1; and 0, 0.5, 1, 2, 4, 6, 8, 12, 24 (Day 8) and 48 (Day 9) hours post-dose on Day 7.

Merck Sharp & Dohme LLC

The All Participants as Treated (APaT) population consisted of all participants who received at least one dose of study drug.

In Cycle 1, participants received MK-8242 60 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling. In Cycle 2 and subsequent cycles, participants received MK-8242 60 mg PO BID on Days 1-7 of each 21-day cycle.

MK-8242 60 mg BID

MK-8242 120 mg BID

MK-8242 170 mg BID

MK-8242 250 mg BID

MK-8242 300 mg BID

MK-8242 350 mg BID

MK-8242 400 mg BID

MK-8242 500 mg BID

Total

Age, Continuous

Sex: Female, Male

Senior Vice President, Global Clinical Development

The DLT-evaluable population consisted of participants who received at least one dose of MK-8242 and completed Cycle 1 of Part 1 (dose escalation) or the dose confirmation portion of Part 2, or discontinued due to toxicity.

Number of Participants With Dose Limiting Toxicities (DLTs)

Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6)

Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3)

Maximum Observed Plasma Concentration (Cmax) of MK-8242

The APaT population consisted of all participants who received at least one dose of study drug.

Spots Global Cancer Trial Database for Study of Safety and Pharmacokinetics of MK-8242 in Participants With Advanced Solid Tumors (P07650)

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