The purposes of this study are to: 1) assess the safety and tolerability and 2) establish a preliminary recommended Phase 2 dose (RP2D) and/or a maximum tolerated dose (MTD) or a maximum administered dose (MAD) of MK-2118 when administered via intratumoral (IT) injection as monotherapy and in combination with pembrolizumab (MK-3475) intravenous (IV) infusion, or via subcutaneous (SC) injection in combination with pembrolizumab IV infusion in the treatment of adult participants with advanced/metastatic solid tumors or lymphomas. Participants will receive either MK-2118 monotherapy or MK-2118 in combination with pembrolizumab for up to 35 cycles for Arms 1-3 or up to 36 cycles for Arm 4 (up to approximately 2 years). All participants will undergo at least a 24-hour observation period following the first three administrations of MK-2118 (Arms 1-3: Cycle 1 Days 1, 8, and 15. Arm 4: Cycle 1 Days 1 and 8; and Cycle 2 Day 1). Qualified participants who experience radiographic or clinical progression in Arm 1 (MK-2118 Intra-tumoral \[IT\] monotherapy) may switch over to Arm 2 (MK-2118 IT + Pembrolizumab IV Combination Therapy) at an eligible dose. Pharmacokinetic (PK) outcome measures will not be analyzed separately for the switch-over treatment arms, per protocol.
Arm 3 did not enroll any participants. Data for the pembrolizumab Cmin outcome measure were not collected.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
140
University of California San Diego Moores Cancer Center ( Site 0004)
La Jolla, California, United States
UCLA ( Site 0003)
Los Angeles, California, United States
University of Chicago ( Site 0002)
Chicago, Illinois, United States
New York Presbyterian Hospital/Columbia University ( Site 0001)
New York, New York, United States
UPMC Hillman Cancer Centers ( Site 0007)
Pittsburgh, Pennsylvania, United States
Mary Crowley Cancer Research Center ( Site 0005)
Dallas, Texas, United States
MD Anderson Cancer Centr. ( Site 0006)
Houston, Texas, United States
Sheba Medical Center ( Site 0301)
Ramat Gan, Israel
Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs)
A DLT is defined as the following toxicities, if related to study treatment: Grade 4 nonhematologic toxicity; Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia (Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with significant bleeding); non-hematologic adverse event (AE) ≥Grade 3 (with exceptions); Grade 3 or Grade 4 nonhematologic abnormality; febrile neutropenia Grade 3 or 4; any toxicity causing treatment discontinuation or missing ≥1 dose; any toxicity causing a \>2 week delay initiating pembrolizumab; any elevated aspartate aminotransferase or alanine aminotransferase value that is ≥3× upper limit of normal (ULN) and an elevated total bilirubin value that is ≥2× ULN \& an alkaline phosphatase value that is \<2× ULN with no alternative explanation; any ≥Grade 2 immune-mediated uveitis; Grade 5 toxicity. Per protocol, DLTs were analyzed separately for the switch-over treatment arms. The number of participants who experienced one or more DLTs is reported.
Time frame: Up to ~35 days
Number of Participants Who Experience One or More Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Per protocol, safety was analyzed separately for the switch-over treatment arms. The number of participants who experienced one or more AEs is reported.
Time frame: Up to ~65 months
Number of Participants Who Discontinue Study Treatment Due to an AE
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Per protocol, tolerability was analyzed separately for the switch-over treatment arms. The number of participants who discontinued study treatment due to an AE is reported.
Time frame: Up to ~27 months
MK-2118 Minimum Plasma Concentration (Cmin)
Cmin of MK-2118 was defined as the minimum concentration of MK-2118 observed in plasma. Blood samples were collected pre-dose and at specified timepoints post dose for estimation of MK-2118 Cmin. Per protocol, PK outcomes were not analyzed separately for the switch-over treatment arms.
Time frame: Cycle 1 Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 12, 24 hours postdose; Cycle 2 Day 1, Cycle 3 Day 1: Predose, 0.5, 1, 2, 4, 6, 8 hours postdose (Arms 1 and 2: length of Cycle= 3 weeks, Arm 4: length of Cycle 1= 2 weeks, length of Cycles 2 and 3= 3 weeks)
MK-2118 Maximum Plasma Concentration (Cmax)
Cmax of MK-2118 was defined as the maximum concentration of MK-2118 observed in plasma. Blood samples were collected pre-dose and at specified timepoints post dose for estimation of MK-2118 Cmax. Per protocol, PK outcomes were not analyzed separately for the switch-over treatment arms.
Time frame: Cycle 1 Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 12, 24 hours postdose; Cycle 2 Day 1, Cycle 3 Day 1: Predose, 0.5, 1, 2, 4, 6, 8 hours postdose (Arms 1 and 2: length of Cycle= 3 weeks, Arm 4: length of Cycle 1= 2 weeks, length of Cycles 2 and 3= 3 weeks)
MK-2118 Area Under the Concentration-time Curve From 0 to 24 Hours (AUC 0-24 Hours)
AUC 0-24 hours of MK-2118 was defined as a measure of MK-2118 exposure that was calculated as the product of plasma drug concentration and time. Blood samples were collected pre-dose and at specified timepoints post dose for estimation of MK-2118 AUC0-24 hours. Per protocol, PK outcomes were not analyzed separately for the switch-over treatment arms.
Time frame: Cycle 1 Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 12, 24 hours postdose; Cycle 2 Day 1, Cycle 3 Day 1: Predose, 0.5, 1, 2, 4, 6, 8 hours postdose (Arms 1 and 2: length of Cycle= 3 weeks, Arm 4: length of Cycle 1= 2 weeks, length of Cycles 2 and 3= 3 weeks)
Pembrolizumab Minimum Plasma Concentration (Cmin)
Cmin of pembrolizumab was defined as the minimum concentration of pembrolizumab observed in plasma. Blood samples were to be collected at specified timepoints for estimation of pembrolizumab Cmin. Per protocol, analysis of pembrolizumab Cmin was not planned in Arm 1 (MK-2118 IT Monotherapy) or for the switch-over treatment arms. For Arm 2 (MK-2118 IT + Pembrolizumab combination) and Arm 4 (MK-2118 SC + Pembrolizumab combination), pembrolizumab Cmin data were not collected.
Time frame: Predose on Day 1 of Cycles 1, 2, 3, 4, 5 and every 4 cycles thereafter (up to ~2 years) (Arm 2: length of Cycle= 3 weeks, Arm 4: length of Cycle 1= 2 weeks, length of Cycles 2 to 36= 3 weeks)
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