This study will examine the safety, pharmacokinetics, and efficacy of escalating doses of selumetinib (MK-5618) in combination with intravenous (IV) pembrolizumab (MK-3475) for participants with advanced / metastatic solid tumors.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
32
Selumetinib oral capsules administered BID at escalating dose levels. Selumetinib administered only in weeks 1\&2 of each 3-week treatment cycle.
Pembrolizumab administered by IV infusion at 200 mg Q3W, given on cycle day 1 of each 3-week treatment cycle.
City of Hope National Medical Center ( Site 0004)
Duarte, California, United States
START Midwest ( Site 0001)
Grand Rapids, Michigan, United States
John Theurer Cancer Center ( Site 0002)
Hackensack, New Jersey, United States
South Texas Accelerated Research Therapeutics, LLC (START) ( Site 0003)
San Antonio, Texas, United States
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
DLT was defined as toxicities that: 1) were possibly, probably, or definitely related to study therapy, excluding toxicities clearly not related to the drug, such as disease progression, environmental factors, unrelated trauma; and 2) met pre-defined severity criteria. For each arm, the number of participants experiencing DLTs were assessed.
Time frame: Up to 21 days
Number of Participants Who Experienced Adverse Event (AE)
An AE was any unfavorable and unintended sign, symptom, or disease (new or exacerbated) in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. For each arm, the number of participants experiencing an AE will be assessed.
Time frame: Up to ~28 months
Number of Participants Discontinuing Study Treatment Due to an Adverse Event
An AE was any unfavorable and unintended sign, symptom, or disease (new or exacerbated) in a clinical study participant, temporally associated withthe use of study treatment, whether or not considered related to the study treatment. For each arm, the number of participants discontinuing study treatment due to an AE was assessed.
Time frame: Up to ~28 months
Area Under the Concentration-Time Curve (AUC) of Selumetinib.
Plasma selumetinib concentration was quantified for each arm to determine AUC, defined as the area under the concentration-time curve for selumetinib. AUC(0-last) is area under the concentration-time curve from dosing (time 0) to the time of the last measured concentration. AUC (0-12) is area under the concentration-time curve from dosing (time 0) to 12 hours.
Time frame: Pre-dose, 1, 2, 4, 6, between 8 and 12 hours post dose on Day 1; Time 0 pre-dose at Cycle 2 Day 1, Cycle 2 Day 14, Cycle 5 Day 1 and Cycle 5 Day 14.
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Princess Margaret Cancer Centre ( Site 0014)
Toronto, Ontario, Canada
CHU de Quebec Universite de Laval ( Site 0013)
Québec, Quebec, Canada
Maximum Observed Plasma Concentration (Cmax) of Selumetinib
Plasma selumetinib concentration was quantified for each arm to determine Cmax, defined as the maximum observed concentration of selumetinib in plasma.
Time frame: Pre-dose, 1, 2, 4, 6, between 8 and 12 hours post dose on Day 1; Time 0 pre-dose at Cycle 2 Day 1, Cycle 2 Day 14, Cycle 5 Day 1 and Cycle 5 Day 14.
Minimum Observed Plasma Concentration (Cmin) of Selumetinib
Plasma selumetinib concentration was quantified for each arm to determine Cmin, defined as the minimum observed concentration of selumetinib in plasma.
Time frame: Pre-dose, 1, 2, 4, 6, between 8 and 12 hours post dose on Day 1; Time 0 pre-dose at Cycle 2 Day 1, Cycle 2 Day 14, Cycle 5 Day 1 and Cycle 5 Day 14.