Lymphoma, Solid Tumor
Conditions
Brief summary
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.
Detailed description
Arm 3 did not enroll any participants. Data for the pembrolizumab Cmin outcome measure were not collected.
Interventions
DRUGMK-2118 (IT)
IT injection
DRUGMK-2118 (SC)
SC injection
BIOLOGICALPembrolizumab
IV infusion
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Arms 1 and 2 Participants: * Has any histologically or cytologically confirmed advanced/metastatic solid tumor by pathology report and has received, or have been intolerant to all treatment known to confer clinical benefit. Solid tumors and lymphomas of any type are eligible for enrollment. For cutaneous T-cell lymphoma (CTCL), histopathological diagnosis should be confirmed in a skin biopsy representative of disease. * Has Stage III or Stage IV disease that is not surgically resectable. Stage IIB (T3N0M0B0-1) CTCL participants are eligible. Arm 3 Participants: \- Has metastatic liver and/or liver lesion involvement that does not exceed one third of the total liver volume in participants to be treated by liver IT injection. Hepatocellular carcinoma participants are excluded from eligibility of IT liver injection. All Participants: * Has Stage III or Stage IV disease that is not surgically resectable. * Has ≥1 injectable lesion that is amenable to injection and biopsy via visual inspection for a cutaneous lesion, or via ultrasound guidance for a subcutaneous lesion. * Has ≥1 discrete, distant noninjected lesion that is amenable to biopsy via visual inspection or amenable to biopsy via image guidance. * Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. * Demonstrates adequate organ function. * A male participant is eligible to participate if he agrees to the following during the intervention period and for at least 120 days after the last dose of study intervetnion: 1. Refrain from donating sperm. 2. Be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent OR must agree to use contraception unless confirmed to be azoospermic. * A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: 1. Is not a woman of childbearing potential (WOCBP). 2. Is a WOCBP and using a contraceptive method that is highly effective with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), during the intervention period and for at least 120 days after the last dose of study intervention, AND agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. * Human Immunodeficiency Virus (HIV)-infected participants must meet these additional criteria: 1. Has HIV-1 infection documented by laboratory test. 2. Has well-controlled HIV on antiretroviral therapy (ART), defined as: 1) must have a CD4+ T-cell count \>350 cells/mm\^3 at time of screening; 2) must have achieved and maintained virologic suppression defined as confirmed HIV ribonucleic acid (RNA) level \<50 or below the lower limit of quantification (LLOQ) using the locally available assay at the time of screening and for ≥12 weeks prior to screening; and 3) must have been on a stable regimen, without changes in drugs or dose modification, for ≥4 weeks prior to study entry (Day 1).
Exclusion criteria
* Has history of a second malignancy, unless potentially curative treatment has been completed, with no evidence of malignancy for 2 years (except for successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, or in situ cervical cancer). * Has clinically active central nervous system metastases and/or carcinomatous meningitis. * Has severe hypersensitivity reaction to treatment with a monoclonal antibody (mAb). * Has active autoimmune disease that has required systemic treatment in the past 2 years. * Has history of vasculitis. * Has active infection requiring therapy. * Has history of (noninfectious) pneumonitis that required steroids or current pneumonitis. * Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years. * Has known Hepatitis B or C infection. * Has known psychiatric or substance abuse disorders that would interfere in cooperation with the requirements of the trial. * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study. * Is not fully recovered from any effects of major surgery, and is free of significant detectable infection. * HIV-infected participants with history of Kaposi's sarcoma and/or multicentric Castleman's disease. * HIV-infected participants who have had an HIV-related opportunistic infection within 6 months. * Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to the first dose of study treatment, or has not recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 from the AEs due to cancer therapeutics administered \>4 weeks earlier. * Has been treated within 2 weeks of Cycle 1 Day1 with any of the following: strong/moderate Cytochrome P450 2C9 (CYP2C9) inhibitors, such as: amiodarone, felbamate, fluconazole, miconazole, piperine, oxandrolone, fluorouracil and its derivatives (combination drug tegafur/gimeracil/oteracil \[TS-1\], Uftoral \[UFT\], tegafur, carmofur, doxifluridine, capecitabine), sulfaphenazole, cyclosporine, bucurol, tienilic acid; UGT1A3 inhibitors (including ritonavir, quinidine, probenecid, and valproic acid); or strong carbonyl reductase (CBR) inhibitors (including quercetin, menadione, glycyrrhetinic acid, and flufenamic acid). * Is currently participating and receiving study therapy or has participated in a study of an investigational agent and has received study therapy or has used an investigational device within 28 days of administration of MK-2118. * Is expected to require any other form of antineoplastic therapy while on study. * Is on chronic systemic steroid therapy in excess of replacement doses (prednisone ≤10 mg/day is acceptable), or on any other form of immunosuppressive medication. For CTCL, continued use of either prednisone ≤10 mg/day or continued use of topical steroids is acceptable. * Has received a live vaccine within 28 days prior to first dose. * Has been treated with a stimulator of interferon genes (STING) agonist (eg, MK-1454, ADU-S100 \[synthetic cyclic dinucleotide (CDN)\]). * Has a history of re-irradiation for head and neck squamous cell carcinoma (HNSCC) at the projected injection site. * Has a tumor(s) in direct contact or encases a major blood vessel and has ulceration and/or fungation onto the skin surface at the projected injection site.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | Up to ~35 days | 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. |
| Number of Participants Who Experience One or More Adverse Events (AEs) | Up to ~65 months | 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. |
| Number of Participants Who Discontinue Study Treatment Due to an AE | Up to ~27 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MK-2118 Minimum Plasma Concentration (Cmin) | 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) | 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. |
| Pembrolizumab Minimum Plasma Concentration (Cmin) | 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) | 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. |
| MK-2118 Maximum Plasma Concentration (Cmax) | 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) | 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. |
| MK-2118 Area Under the Concentration-time Curve From 0 to 24 Hours (AUC 0-24 Hours) | 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) | 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. |
Countries
Israel, United States
Participant flow
Pre-assignment details
Arm 3 did not enroll any participants. Per protocol, pharmacokinetic (PK) outcome measures were not analyzed separately for the switch-over treatment arms.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 MK-2118 100 μg Intra-tumoral (IT) Monotherapy Participants received MK-2118 100 μg via IT injection once weekly (Q1W) on Days 1, 8 and 15 of Cycles 1-3 followed by once every 3 weeks (Q3W) on Day 1 of Cycle 4 and beyond, for a total of up to \
35 cycles (up to \
2 years). Each cycle is 3 weeks long. | 1 |
| Arm 1 MK-2118 300 μg IT Monotherapy Participants received MK-2118 300 μg via IT injection Q1W on Days 1, 8 and 15 of Cycles 1-3 followed by Q3W on Day 1 of Cycle 4 and beyond, for a total of up to \
35 cycles (up to \
2 years). Each cycle is 3 weeks long. | 1 |
| Arm 1 MK-2118 900 μg IT Monotherapy Participants received MK-2118 900 μg via IT injection Q1W on Days 1, 8 and 15 of Cycles 1-3 followed by Q3W on Day 1 of Cycle 4 and beyond, for a total of up to \
35 cycles (up to \
2 years). Each cycle is 3 weeks long. | 1 |
| Arm 1 MK-2118 2700 μg IT Monotherapy Participants received MK-2118 2700 μg via IT injection Q1W on Days 1, 8 and 15 of Cycles 1-3 followed by Q3W on Day 1 of Cycle 4 and beyond, for a total of up to \
35 cycles (up to \
2 years). Each cycle is 3 weeks long. | 2 |
| Arm 1 MK-2118 5400 μg IT Monotherapy Participants received MK-2118 5400 μg via IT injection Q1W on Days 1, 8 and 15 of Cycles 1-3 followed by Q3W on Day 1 of Cycle 4 and beyond, for a total of up to \
35 cycles (up to \
2 years). Each cycle is 3 weeks long. | 3 |
| Arm 1 MK-2118 7700 μg IT Monotherapy Participants received MK-2118 7700 μg via IT injection Q1W on Days 1, 8 and 15 of Cycles 1-3 followed by Q3W on Day 1 of Cycle 4 and beyond, for a total of up to \
35 cycles (up to \
2 years). Each cycle is 3 weeks long. | 3 |
| Arm 1 MK-2118 10000 μg IT Monotherapy Participants received MK-2118 10000 μg via IT injection Q1W on Days 1, 8 and 15 of Cycles 1-3 followed by Q3W on Day 1 of Cycle 4 and beyond, for a total of up to \
35 cycles (up to \
2 years). Each cycle is 3 weeks long. | 6 |
| Arm 1 MK-2118 15000 μg IT Monotherapy Participants received MK-2118 15000 μg via IT injection Q1W on Days 1, 8 and 15 of Cycles 1-3 followed by Q3W on Day 1 of Cycle 4 and beyond, for a total of up to \
35 cycles (up to \
2 years). Each cycle is 3 weeks long. | 4 |
| Arm 1 MK-2118 20000 μg IT Monotherapy Participants received MK-2118 20000 μg via IT injection Q1W on Days 1, 8 and 15 of Cycles 1-3 followed by Q3W on Day 1 of Cycle 4 and beyond, for a total of up to \
35 cycles (up to \
2 years). Each cycle is 3 weeks long. | 6 |
| Arm 2 MK-2118 2700 μg IT + Pembrolizumab 200 mg IV Combination Therapy Participants received MK-2118 2700 μg via IT injection Q1W on Days 1, 8 and 15 of Cycles 1-3 followed by Q3W on Day 1 of Cycle 4 and beyond, for a total of up to \
35 cycles (up to \
2 years) and received pembrolizumab 200 mg via IV infusion on Day 1 of each cycle for a total of up to \
35 cycles (up to \
2 years). Each cycle is 3 weeks long. | 2 |
| Arm 2 MK-2118 5400 μg IT + Pembrolizumab 200 mg IV Combination Therapy Participants received MK-2118 5400 μg via IT injection Q1W on Days 1, 8 and 15 of Cycles 1-3 followed by Q3W on Day 1 of Cycle 4 and beyond, for a total of up to \
35 cycles (up to \
2 years) and received pembrolizumab 200 mg via IV infusion on Day 1 of each cycle for a total of up to \
35 cycles (up to \
2 years). Each cycle is 3 weeks long. | 13 |
| Arm 2 MK-2118 7700 μg IT + Pembrolizumab 200 mg IV Combination Therapy Participants received MK-2118 7700 μg via IT injection Q1W on Days 1, 8 and 15 of Cycles 1-3 followed by Q3W on Day 1 of Cycle 4 and beyond, for a total of up to \
35 cycles (up to \
2 years) and received pembrolizumab 200 mg via IV infusion on Day 1 of each cycle for a total of up to \
35 cycles (up to \
2 years). Each cycle is 3 weeks long. | 11 |
| Arm 2 MK-2118 10000 μg IT + Pembrolizumab 200 mg IV Combination Therapy Participants received MK-2118 10000 μg via IT injection Q1W on Days 1, 8 and 15 of Cycles 1-3 followed by Q3W on Day 1 of Cycle 4 and beyond, for a total of up to \
35 cycles (up to \
2 years) and received pembrolizumab 200 mg via IV infusion on Day 1 of each cycle for a total of up to \
35 cycles (up to \
2 years). Each cycle is 3 weeks long. | 18 |
| Arm 2 MK-2118 15000 μg IT + Pembrolizumab 200 mg IV Combination Therapy Participants received MK-2118 15000 μg via IT injection Q1W on Days 1, 8 and 15 of Cycles 1-3 followed by Q3W on Day 1 of Cycle 4 and beyond, for a total of up to \
35 cycles (up to \
2 years) and received pembrolizumab 200 mg via IV infusion on Day 1 of each cycle for a total of up to \
35 cycles (up to \
2 years). Each cycle is 3 weeks long. | 13 |
| Arm 4: MK-2118 5000 μg Subcutaneous (SC) + Pembrolizumab 200 mg IV Combination Therapy Participants received MK-2118 5000 μg via SC injection Q1W on Days 1 and 8 of Cycle 1 followed by Q1W on Days 1, 8 and 15 of Cycles 2-4, followed by Q3W on Day 1 of Cycle 5 and beyond, for a total of up to 36 cycles (up to \
2 years) and received pembrolizumab 200 mg via IV infusion on Day 1 of Cycle 2 and beyond for a total of up to 36 cycles (up to \
2 years). Cycle 1 is 2 weeks long and Cycles 2 to 36 are 3 weeks long. | 4 |
| Arm 4: MK-2118 10000 μg SC + Pembrolizumab 200 mg IV Combination Therapy Participants received MK-2118 10000 μg via SC injection Q1W on Days 1 and 8 of Cycle 1 followed by Q1W on Days 1, 8 and 15 of Cycles 2-4, followed by Q3W on Day 1 of Cycle 5 and beyond, for a total of up to 36 cycles (up to \
2 years) and received pembrolizumab 200 mg via IV infusion on Day 1 of Cycle 2 and beyond for a total of up to 36 cycles (up to \
2 years). Cycle 1 is 2 weeks long and Cycles 2 to 36 are 3 weeks long. | 8 |
| Arm 4: MK-2118 15000 μg SC + Pembrolizumab 200 mg IV Combination Therapy Participants received MK-2118 15000 μg via SC injection Q1W on Days 1 and 8 of Cycle 1 followed by Q1W on Days 1, 8 and 15 of Cycles 2-4, followed by Q3W on Day 1 of Cycle 5 and beyond, for a total of up to 36 cycles (up to \
2 years) and received pembrolizumab 200 mg via IV infusion on Day 1 of Cycle 2 and beyond for a total of up to 36 cycles (up to \
2 years). Cycle 1 is 2 weeks long and Cycles 2 to 36 are 3 weeks long. | 14 |
| Arm 4: MK-2118 20000 μg SC + Pembrolizumab 200 mg IV Combination Therapy Participants received MK-2118 20000 μg via SC injection Q1W on Days 1 and 8 of Cycle 1 followed by Q1W on Days 1, 8 and 15 of Cycles 2-4, followed by Q3W on Day 1 of Cycle 5 and beyond, for a total of up to 36 cycles (up to \
2 years) and received pembrolizumab 200 mg via IV infusion on Day 1 of Cycle 2 and beyond for a total of up to 36 cycles (up to \
2 years). Cycle 1 is 2 weeks long and Cycles 2 to 36 are 3 weeks long. | 7 |
| Arm 4: MK-2118 30000 μg SC + Pembrolizumab 200 mg IV Combination Therapy Participants received MK-2118 30000 μg via SC injection Q1W on Days 1 and 8 of Cycle 1 followed by Q1W on Days 1, 8 and 15 of Cycles 2-4, followed by Q3W on Day 1 of Cycle 5 and beyond, for a total of up to 36 cycles (up to \
2 years) and received pembrolizumab 200 mg via IV infusion on Day 1 of Cycle 2 and beyond for a total of up to 36 cycles (up to \
2 years). Cycle 1 is 2 weeks long and Cycles 2 to 36 are 3 weeks long. | 6 |
| Arm 4: MK-2118 45000 μg SC + Pembrolizumab 200 mg IV Combination Therapy Participants received MK-2118 45000 μg via SC injection Q1W on Days 1 and 8 of Cycle 1 followed by Q1W on Days 1, 8 and 15 of Cycles 2-4, followed by Q3W on Day 1 of Cycle 5 and beyond, for a total of up to 36 cycles (up to \
2 years) and received pembrolizumab 200 mg via IV infusion on Day 1 of Cycle 2 and beyond for a total of up to 36 cycles (up to \
2 years). Cycle 1 is 2 weeks long and Cycles 2 to 36 are 3 weeks long. | 3 |
| Arm 4: MK-2118 60000 μg SC + Pembrolizumab 200 mg IV Combination Therapy Participants received MK-2118 60000 μg via SC injection Q1W on Days 1 and 8 of Cycle 1 followed by Q1W on Days 1, 8 and 15 of Cycles 2-4, followed by Q3W on Day 1 of Cycle 5 and beyond, for a total of up to 36 cycles (up to \
2 years) and received pembrolizumab 200 mg via IV infusion on Day 1 of Cycle 2 and beyond for a total of up to 36 cycles (up to \
2 years). Cycle 1 is 2 weeks long and Cycles 2 to 36 are 3 weeks long. | 3 |
| Arm 4: MK-2118 90000 μg SC + Pembrolizumab 200 mg IV Combination Therapy Participants received MK-2118 90000 μg via SC injection Q1W on Days 1 and 8 of Cycle 1 followed by Q1W on Days 1, 8 and 15 of Cycles 2-4, followed by Q3W on Day 1 of Cycle 5 and beyond, for a total of up to 36 cycles (up to \
2 years) and received pembrolizumab 200 mg via IV infusion on Day 1 of Cycle 2 and beyond for a total of up to 36 cycles (up to \
2 years). Cycle 1 is 2 weeks long and Cycles 2 to 36 are 3 weeks long. | 3 |
| Arm 4: MK-2118 120000 μg SC + Pembrolizumab 200 mg IV Combination Therapy Participants received MK-2118 120000 μg via SC injection Q1W on Days 1 and 8 of Cycle 1 followed by Q1W on Days 1, 8 and 15 of Cycles 2-4, followed by Q3W on Day 1 of Cycle 5 and beyond, for a total of up to 36 cycles (up to \
2 years) and received pembrolizumab 200 mg via IV infusion on Day 1 of Cycle 2 and beyond for a total of up to 36 cycles (up to \
2 years). Cycle 1 is 2 weeks long and Cycles 2 to 36 are 3 weeks long. | 4 |
| Arm 4: MK-2118 150000 μg SC + Pembrolizumab 200 mg IV Combination Therapy Participants received MK-2118 150000 μg via SC injection Q1W on Days 1 and 8 of Cycle 1 followed by Q1W on Days 1, 8 and 15 of Cycles 2-4, followed by Q3W on Day 1 of Cycle 5 and beyond, for a total of up to 36 cycles (up to \
2 years) and received pembrolizumab 200 mg via IV infusion on Day 1 of Cycle 2 and beyond for a total of up to 36 cycles (up to \
2 years). Cycle 1 is 2 weeks long and Cycles 2 to 36 are 3 weeks long. | 4 |
| Total | 140 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 | FG019 | FG020 | FG021 | FG022 | FG023 | FG024 | FG025 | FG026 | FG027 | FG028 | FG029 | FG030 | FG031 | FG032 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arms 1, 2, and 4 | Death | 1 | 1 | 0 | 2 | 3 | 2 | 2 | 4 | 2 | 1 | 7 | 7 | 12 | 7 | 0 | 4 | 4 | 12 | 6 | 4 | 2 | 3 | 1 | 1 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Arms 1, 2, and 4 | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Arms 1, 2, and 4 | Sponsor Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 1 | 1 | 3 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Arms 1, 2, and 4 | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 1 | 4 | 0 | 2 | 1 | 4 | 3 | 5 | 3 | 0 | 0 | 3 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Switch Over Period | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Switch Over Period | Progressive Disease | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 2 | 1 | 0 | 1 |
| Switch Over Period | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Arm 1 MK-2118 300 μg IT Monotherapy | Arm 1 MK-2118 900 μg IT Monotherapy | Arm 1 MK-2118 2700 μg IT Monotherapy | Arm 1 MK-2118 5400 μg IT Monotherapy | Arm 1 MK-2118 7700 μg IT Monotherapy | Arm 1 MK-2118 10000 μg IT Monotherapy | Arm 1 MK-2118 15000 μg IT Monotherapy | Arm 1 MK-2118 20000 μg IT Monotherapy | Arm 2 MK-2118 2700 μg IT + Pembrolizumab 200 mg IV Combination Therapy | Arm 2 MK-2118 5400 μg IT + Pembrolizumab 200 mg IV Combination Therapy | Arm 2 MK-2118 7700 μg IT + Pembrolizumab 200 mg IV Combination Therapy | Arm 2 MK-2118 10000 μg IT + Pembrolizumab 200 mg IV Combination Therapy | Arm 2 MK-2118 15000 μg IT + Pembrolizumab 200 mg IV Combination Therapy | Arm 4: MK-2118 5000 μg Subcutaneous (SC) + Pembrolizumab 200 mg IV Combination Therapy | Arm 4: MK-2118 10000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Arm 4: MK-2118 15000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Arm 4: MK-2118 20000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Arm 4: MK-2118 30000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Arm 1 MK-2118 100 μg Intra-tumoral (IT) Monotherapy | Arm 4: MK-2118 45000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Arm 4: MK-2118 60000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Arm 4: MK-2118 90000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Arm 4: MK-2118 120000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Arm 4: MK-2118 150000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 0 to 17 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 18 to 64 years | 0 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 4 Participants | 2 Participants | 4 Participants | 2 Participants | 9 Participants | 7 Participants | 9 Participants | 10 Participants | 3 Participants | 4 Participants | 13 Participants | 6 Participants | 4 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 93 Participants |
| Age, Customized 65 to 84 years | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 0 Participants | 4 Participants | 4 Participants | 8 Participants | 3 Participants | 1 Participants | 4 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 3 Participants | 44 Participants |
| Age, Customized 85 years and over | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 3 Participants | 6 Participants | 4 Participants | 6 Participants | 2 Participants | 13 Participants | 11 Participants | 18 Participants | 13 Participants | 4 Participants | 8 Participants | 14 Participants | 7 Participants | 6 Participants | 1 Participants | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 4 Participants | 140 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 3 Participants | 6 Participants | 4 Participants | 6 Participants | 2 Participants | 13 Participants | 11 Participants | 18 Participants | 13 Participants | 4 Participants | 8 Participants | 14 Participants | 7 Participants | 6 Participants | 1 Participants | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 4 Participants | 140 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants | 3 Participants | 1 Participants | 2 Participants | 1 Participants | 7 Participants | 4 Participants | 11 Participants | 7 Participants | 1 Participants | 4 Participants | 5 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 3 Participants | 61 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 3 Participants | 3 Participants | 4 Participants | 1 Participants | 6 Participants | 7 Participants | 7 Participants | 6 Participants | 3 Participants | 4 Participants | 9 Participants | 7 Participants | 5 Participants | 1 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk | EG021 affected / at risk | EG022 affected / at risk | EG023 affected / at risk | EG024 affected / at risk | EG025 affected / at risk | EG026 affected / at risk | EG027 affected / at risk | EG028 affected / at risk | EG029 affected / at risk | EG030 affected / at risk | EG031 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 1 | 1 / 1 | 0 / 1 | 2 / 2 | 3 / 3 | 2 / 3 | 5 / 6 | 4 / 4 | 4 / 6 | 2 / 2 | 8 / 13 | 9 / 11 | 13 / 18 | 9 / 13 | 4 / 4 | 6 / 8 | 12 / 14 | 6 / 7 | 4 / 6 | 2 / 3 | 3 / 3 | 1 / 3 | 1 / 4 | 4 / 4 | 1 / 1 | 1 / 1 | 1 / 1 | 0 / 1 | 1 / 2 | 1 / 1 | 0 / 1 | 1 / 1 |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 1 / 1 | 2 / 2 | 3 / 3 | 3 / 3 | 6 / 6 | 4 / 4 | 6 / 6 | 2 / 2 | 13 / 13 | 11 / 11 | 16 / 16 | 12 / 13 | 4 / 4 | 8 / 8 | 14 / 14 | 6 / 7 | 6 / 6 | 3 / 3 | 3 / 3 | 3 / 3 | 4 / 4 | 4 / 4 | 1 / 1 | 1 / 1 | 0 / 1 | 1 / 1 | 2 / 2 | 1 / 1 | 1 / 1 | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 | 0 / 1 | 0 / 1 | 0 / 2 | 2 / 3 | 0 / 3 | 3 / 6 | 1 / 4 | 1 / 6 | 1 / 2 | 4 / 13 | 6 / 11 | 13 / 16 | 6 / 13 | 0 / 4 | 2 / 8 | 2 / 14 | 1 / 7 | 3 / 6 | 2 / 3 | 0 / 3 | 0 / 3 | 3 / 4 | 3 / 4 | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 1 | 1 / 2 | 0 / 1 | 0 / 1 | 1 / 1 |
Outcome results
Primary
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
Population: All allocated participants who received ≥1 dose of study treatment. Per protocol, tolerability was analyzed separately for the switch-over treatment arms.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1 MK-2118 100 μg Intra-tumoral (IT) Monotherapy | Number of Participants Who Discontinue Study Treatment Due to an AE | 0 Participants |
| Arm 1 MK-2118 300 μg IT Monotherapy | Number of Participants Who Discontinue Study Treatment Due to an AE | 0 Participants |
| Arm 1 MK-2118 900 μg IT Monotherapy | Number of Participants Who Discontinue Study Treatment Due to an AE | 0 Participants |
| Arm 1 MK-2118 2700 μg IT Monotherapy | Number of Participants Who Discontinue Study Treatment Due to an AE | 0 Participants |
| Arm 1 MK-2118 5400 μg IT Monotherapy | Number of Participants Who Discontinue Study Treatment Due to an AE | 0 Participants |
| Arm 1 MK-2118 7700 μg IT Monotherapy | Number of Participants Who Discontinue Study Treatment Due to an AE | 0 Participants |
| Arm 1 MK-2118 10000 μg IT Monotherapy | Number of Participants Who Discontinue Study Treatment Due to an AE | 0 Participants |
| Arm 1 MK-2118 15000 μg IT Monotherapy | Number of Participants Who Discontinue Study Treatment Due to an AE | 1 Participants |
| Arm 1 MK-2118 20000 μg IT Monotherapy | Number of Participants Who Discontinue Study Treatment Due to an AE | 1 Participants |
| Arm 2 MK-2118 2700 μg IT + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Discontinue Study Treatment Due to an AE | 0 Participants |
| Arm 2 MK-2118 5400 μg IT + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Discontinue Study Treatment Due to an AE | 1 Participants |
| Arm 2 MK-2118 7700 μg IT + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Discontinue Study Treatment Due to an AE | 1 Participants |
| Arm 2 MK-2118 10000 μg IT + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Discontinue Study Treatment Due to an AE | 1 Participants |
| Arm 2 MK-2118 15000 μg IT + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Discontinue Study Treatment Due to an AE | 2 Participants |
| Arm 4: MK-2118 5000 μg Subcutaneous (SC) + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Discontinue Study Treatment Due to an AE | 0 Participants |
| Arm 4: MK-2118 10000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Discontinue Study Treatment Due to an AE | 1 Participants |
| Arm 4: MK-2118 15000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Discontinue Study Treatment Due to an AE | 0 Participants |
| Arm 4: MK-2118 20000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Discontinue Study Treatment Due to an AE | 1 Participants |
| Arm 4: MK-2118 30000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Discontinue Study Treatment Due to an AE | 1 Participants |
| Arm 4: MK-2118 45000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Discontinue Study Treatment Due to an AE | 0 Participants |
| Arm 4: MK-2118 60000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Discontinue Study Treatment Due to an AE | 0 Participants |
| Arm 4: MK-2118 90000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Discontinue Study Treatment Due to an AE | 0 Participants |
| Arm 4: MK-2118 120000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Discontinue Study Treatment Due to an AE | 0 Participants |
| Arm 4: MK-2118 150000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Discontinue Study Treatment Due to an AE | 0 Participants |
| Switch-over Arm 1 MK-2118 300 μg IT To Arm 2 900 μg IT + Pembrolizumab 200 mg IV | Number of Participants Who Discontinue Study Treatment Due to an AE | 1 Participants |
| Switch-over Arm 1 MK-2118 2700 μg IT To Arm 2 2700 μg IT + Pembrolizumab 200 mg IV | Number of Participants Who Discontinue Study Treatment Due to an AE | 0 Participants |
| Switch-over Arm 1 MK-2118 15000 μg IT To Arm 2 5400 μg IT + Pembrolizumab 200 mg IV | Number of Participants Who Discontinue Study Treatment Due to an AE | 0 Participants |
| Switch-over Arm 1 MK-2118 900 μg IT To Arm 2 7700 μg IT + Pembrolizumab 200 mg IV | Number of Participants Who Discontinue Study Treatment Due to an AE | 0 Participants |
| Switch-over Arm 1 MK-2118 7700 μg IT To Arm 2 7700 μg IT + Pembrolizumab 200 mg IV | Number of Participants Who Discontinue Study Treatment Due to an AE | 0 Participants |
| Switch-over Arm 1 MK-2118 15000 μg IT To Arm 2 10000 μg IT + Pembrolizumab 200 mg IV | Number of Participants Who Discontinue Study Treatment Due to an AE | 0 Participants |
| Switch-over Arm 1 MK-2118 20000 μg IT To Arm 2 10000 μg IT + Pembrolizumab 200 mg IV | Number of Participants Who Discontinue Study Treatment Due to an AE | 0 Participants |
| Switch-over Arm 1 MK-2118 20000 μg IT To Arm 2 15000 μg IT + Pembrolizumab 200 mg IV | Number of Participants Who Discontinue Study Treatment Due to an AE | 0 Participants |
Primary
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
Population: All allocated participants who received ≥1 dose of study treatment. Per protocol, safety was analyzed separately for the switch-over treatment arms.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1 MK-2118 100 μg Intra-tumoral (IT) Monotherapy | Number of Participants Who Experience One or More Adverse Events (AEs) | 1 Participants |
| Arm 1 MK-2118 300 μg IT Monotherapy | Number of Participants Who Experience One or More Adverse Events (AEs) | 1 Participants |
| Arm 1 MK-2118 900 μg IT Monotherapy | Number of Participants Who Experience One or More Adverse Events (AEs) | 1 Participants |
| Arm 1 MK-2118 2700 μg IT Monotherapy | Number of Participants Who Experience One or More Adverse Events (AEs) | 2 Participants |
| Arm 1 MK-2118 5400 μg IT Monotherapy | Number of Participants Who Experience One or More Adverse Events (AEs) | 3 Participants |
| Arm 1 MK-2118 7700 μg IT Monotherapy | Number of Participants Who Experience One or More Adverse Events (AEs) | 3 Participants |
| Arm 1 MK-2118 10000 μg IT Monotherapy | Number of Participants Who Experience One or More Adverse Events (AEs) | 6 Participants |
| Arm 1 MK-2118 15000 μg IT Monotherapy | Number of Participants Who Experience One or More Adverse Events (AEs) | 4 Participants |
| Arm 1 MK-2118 20000 μg IT Monotherapy | Number of Participants Who Experience One or More Adverse Events (AEs) | 6 Participants |
| Arm 2 MK-2118 2700 μg IT + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Adverse Events (AEs) | 2 Participants |
| Arm 2 MK-2118 5400 μg IT + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Adverse Events (AEs) | 13 Participants |
| Arm 2 MK-2118 7700 μg IT + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Adverse Events (AEs) | 11 Participants |
| Arm 2 MK-2118 10000 μg IT + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Adverse Events (AEs) | 16 Participants |
| Arm 2 MK-2118 15000 μg IT + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Adverse Events (AEs) | 12 Participants |
| Arm 4: MK-2118 5000 μg Subcutaneous (SC) + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Adverse Events (AEs) | 4 Participants |
| Arm 4: MK-2118 10000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Adverse Events (AEs) | 8 Participants |
| Arm 4: MK-2118 15000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Adverse Events (AEs) | 14 Participants |
| Arm 4: MK-2118 20000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Adverse Events (AEs) | 7 Participants |
| Arm 4: MK-2118 30000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Adverse Events (AEs) | 6 Participants |
| Arm 4: MK-2118 45000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Adverse Events (AEs) | 3 Participants |
| Arm 4: MK-2118 60000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Adverse Events (AEs) | 3 Participants |
| Arm 4: MK-2118 90000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Adverse Events (AEs) | 3 Participants |
| Arm 4: MK-2118 120000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Adverse Events (AEs) | 4 Participants |
| Arm 4: MK-2118 150000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Adverse Events (AEs) | 4 Participants |
| Switch-over Arm 1 MK-2118 300 μg IT To Arm 2 900 μg IT + Pembrolizumab 200 mg IV | Number of Participants Who Experience One or More Adverse Events (AEs) | 1 Participants |
| Switch-over Arm 1 MK-2118 2700 μg IT To Arm 2 2700 μg IT + Pembrolizumab 200 mg IV | Number of Participants Who Experience One or More Adverse Events (AEs) | 1 Participants |
| Switch-over Arm 1 MK-2118 15000 μg IT To Arm 2 5400 μg IT + Pembrolizumab 200 mg IV | Number of Participants Who Experience One or More Adverse Events (AEs) | 0 Participants |
| Switch-over Arm 1 MK-2118 900 μg IT To Arm 2 7700 μg IT + Pembrolizumab 200 mg IV | Number of Participants Who Experience One or More Adverse Events (AEs) | 1 Participants |
| Switch-over Arm 1 MK-2118 7700 μg IT To Arm 2 7700 μg IT + Pembrolizumab 200 mg IV | Number of Participants Who Experience One or More Adverse Events (AEs) | 2 Participants |
| Switch-over Arm 1 MK-2118 15000 μg IT To Arm 2 10000 μg IT + Pembrolizumab 200 mg IV | Number of Participants Who Experience One or More Adverse Events (AEs) | 1 Participants |
| Switch-over Arm 1 MK-2118 20000 μg IT To Arm 2 10000 μg IT + Pembrolizumab 200 mg IV | Number of Participants Who Experience One or More Adverse Events (AEs) | 1 Participants |
| Switch-over Arm 1 MK-2118 20000 μg IT To Arm 2 15000 μg IT + Pembrolizumab 200 mg IV | Number of Participants Who Experience One or More Adverse Events (AEs) | 1 Participants |
Primary
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
Population: All allocated participants who received ≥1 dose of study treatment, who were observed for DLTs for up to 35 days after the first dose of assigned treatment, and had data available for this outcome. Per protocol, DLTs were analyzed separately for the switch-over treatment arms.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1 MK-2118 100 μg Intra-tumoral (IT) Monotherapy | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 0 Participants |
| Arm 1 MK-2118 300 μg IT Monotherapy | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 0 Participants |
| Arm 1 MK-2118 900 μg IT Monotherapy | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 0 Participants |
| Arm 1 MK-2118 2700 μg IT Monotherapy | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 0 Participants |
| Arm 1 MK-2118 5400 μg IT Monotherapy | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 0 Participants |
| Arm 1 MK-2118 7700 μg IT Monotherapy | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 0 Participants |
| Arm 1 MK-2118 10000 μg IT Monotherapy | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 1 Participants |
| Arm 1 MK-2118 15000 μg IT Monotherapy | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 0 Participants |
| Arm 1 MK-2118 20000 μg IT Monotherapy | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 1 Participants |
| Arm 2 MK-2118 2700 μg IT + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 0 Participants |
| Arm 2 MK-2118 5400 μg IT + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 0 Participants |
| Arm 2 MK-2118 7700 μg IT + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 0 Participants |
| Arm 2 MK-2118 10000 μg IT + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 2 Participants |
| Arm 2 MK-2118 15000 μg IT + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 1 Participants |
| Arm 4: MK-2118 5000 μg Subcutaneous (SC) + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 0 Participants |
| Arm 4: MK-2118 10000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 0 Participants |
| Arm 4: MK-2118 15000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 0 Participants |
| Arm 4: MK-2118 20000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 1 Participants |
| Arm 4: MK-2118 30000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 0 Participants |
| Arm 4: MK-2118 45000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 0 Participants |
| Arm 4: MK-2118 60000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 0 Participants |
| Arm 4: MK-2118 90000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 0 Participants |
| Arm 4: MK-2118 120000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 0 Participants |
| Arm 4: MK-2118 150000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 0 Participants |
| Switch-over Arm 1 MK-2118 300 μg IT To Arm 2 900 μg IT + Pembrolizumab 200 mg IV | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 0 Participants |
| Switch-over Arm 1 MK-2118 2700 μg IT To Arm 2 2700 μg IT + Pembrolizumab 200 mg IV | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 0 Participants |
| Switch-over Arm 1 MK-2118 15000 μg IT To Arm 2 5400 μg IT + Pembrolizumab 200 mg IV | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 0 Participants |
| Switch-over Arm 1 MK-2118 900 μg IT To Arm 2 7700 μg IT + Pembrolizumab 200 mg IV | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 0 Participants |
| Switch-over Arm 1 MK-2118 7700 μg IT To Arm 2 7700 μg IT + Pembrolizumab 200 mg IV | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 0 Participants |
| Switch-over Arm 1 MK-2118 15000 μg IT To Arm 2 10000 μg IT + Pembrolizumab 200 mg IV | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 0 Participants |
| Switch-over Arm 1 MK-2118 20000 μg IT To Arm 2 10000 μg IT + Pembrolizumab 200 mg IV | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 1 Participants |
| Switch-over Arm 1 MK-2118 20000 μg IT To Arm 2 15000 μg IT + Pembrolizumab 200 mg IV | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLTs) | 0 Participants |
Secondary
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)
Population: The subset of participants who complied with the protocol and had MK-2118 AUC0-24 hours data available. Per protocol, PK outcomes were not analyzed separately for the switch-over treatment arms.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 MK-2118 100 μg Intra-tumoral (IT) Monotherapy | MK-2118 Area Under the Concentration-time Curve From 0 to 24 Hours (AUC 0-24 Hours) | 7 hour*ng/mL | — |
| Arm 1 MK-2118 300 μg IT Monotherapy | MK-2118 Area Under the Concentration-time Curve From 0 to 24 Hours (AUC 0-24 Hours) | 169 hour*ng/mL | — |
| Arm 1 MK-2118 900 μg IT Monotherapy | MK-2118 Area Under the Concentration-time Curve From 0 to 24 Hours (AUC 0-24 Hours) | 314 hour*ng/mL | — |
| Arm 1 MK-2118 2700 μg IT Monotherapy | MK-2118 Area Under the Concentration-time Curve From 0 to 24 Hours (AUC 0-24 Hours) | 420 hour*ng/mL | Geometric Coefficient of Variation 181 |
| Arm 1 MK-2118 5400 μg IT Monotherapy | MK-2118 Area Under the Concentration-time Curve From 0 to 24 Hours (AUC 0-24 Hours) | 1484 hour*ng/mL | Geometric Coefficient of Variation 36 |
| Arm 1 MK-2118 7700 μg IT Monotherapy | MK-2118 Area Under the Concentration-time Curve From 0 to 24 Hours (AUC 0-24 Hours) | 2777 hour*ng/mL | Geometric Coefficient of Variation 59 |
| Arm 1 MK-2118 10000 μg IT Monotherapy | MK-2118 Area Under the Concentration-time Curve From 0 to 24 Hours (AUC 0-24 Hours) | 2959 hour*ng/mL | Geometric Coefficient of Variation 92 |
| Arm 1 MK-2118 15000 μg IT Monotherapy | MK-2118 Area Under the Concentration-time Curve From 0 to 24 Hours (AUC 0-24 Hours) | 4478 hour*ng/mL | Geometric Coefficient of Variation 34 |
| Arm 1 MK-2118 20000 μg IT Monotherapy | MK-2118 Area Under the Concentration-time Curve From 0 to 24 Hours (AUC 0-24 Hours) | 6210 hour*ng/mL | Geometric Coefficient of Variation 47 |
| Arm 2 MK-2118 2700 μg IT + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Area Under the Concentration-time Curve From 0 to 24 Hours (AUC 0-24 Hours) | 944 hour*ng/mL | Geometric Coefficient of Variation 13 |
| Arm 2 MK-2118 5400 μg IT + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Area Under the Concentration-time Curve From 0 to 24 Hours (AUC 0-24 Hours) | 1217 hour*ng/mL | Geometric Coefficient of Variation 187 |
| Arm 2 MK-2118 7700 μg IT + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Area Under the Concentration-time Curve From 0 to 24 Hours (AUC 0-24 Hours) | 2300 hour*ng/mL | Geometric Coefficient of Variation 78 |
| Arm 2 MK-2118 10000 μg IT + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Area Under the Concentration-time Curve From 0 to 24 Hours (AUC 0-24 Hours) | 3219 hour*ng/mL | Geometric Coefficient of Variation 50 |
| Arm 2 MK-2118 15000 μg IT + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Area Under the Concentration-time Curve From 0 to 24 Hours (AUC 0-24 Hours) | 3993 hour*ng/mL | Geometric Coefficient of Variation 190 |
| Arm 4: MK-2118 5000 μg Subcutaneous (SC) + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Area Under the Concentration-time Curve From 0 to 24 Hours (AUC 0-24 Hours) | 1630 hour*ng/mL | Geometric Coefficient of Variation 18 |
| Arm 4: MK-2118 10000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Area Under the Concentration-time Curve From 0 to 24 Hours (AUC 0-24 Hours) | 3272 hour*ng/mL | Geometric Coefficient of Variation 41 |
| Arm 4: MK-2118 15000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Area Under the Concentration-time Curve From 0 to 24 Hours (AUC 0-24 Hours) | 4518 hour*ng/mL | Geometric Coefficient of Variation 74 |
| Arm 4: MK-2118 20000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Area Under the Concentration-time Curve From 0 to 24 Hours (AUC 0-24 Hours) | 7736 hour*ng/mL | Geometric Coefficient of Variation 26 |
| Arm 4: MK-2118 30000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Area Under the Concentration-time Curve From 0 to 24 Hours (AUC 0-24 Hours) | 13866 hour*ng/mL | Geometric Coefficient of Variation 31 |
| Arm 4: MK-2118 45000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Area Under the Concentration-time Curve From 0 to 24 Hours (AUC 0-24 Hours) | 19257 hour*ng/mL | Geometric Coefficient of Variation 6 |
| Arm 4: MK-2118 60000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Area Under the Concentration-time Curve From 0 to 24 Hours (AUC 0-24 Hours) | 19946 hour*ng/mL | Geometric Coefficient of Variation 19 |
| Arm 4: MK-2118 90000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Area Under the Concentration-time Curve From 0 to 24 Hours (AUC 0-24 Hours) | 29638 hour*ng/mL | Geometric Coefficient of Variation 67 |
| Arm 4: MK-2118 120000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Area Under the Concentration-time Curve From 0 to 24 Hours (AUC 0-24 Hours) | 73573 hour*ng/mL | Geometric Coefficient of Variation 51 |
| Arm 4: MK-2118 150000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Area Under the Concentration-time Curve From 0 to 24 Hours (AUC 0-24 Hours) | 75171 hour*ng/mL | Geometric Coefficient of Variation 46 |
Secondary
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)
Population: The subset of participants who complied with the protocol and had MK-2118 Cmax data available. Per protocol, PK outcomes were not analyzed separately for the switch-over treatment arms.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 MK-2118 100 μg Intra-tumoral (IT) Monotherapy | MK-2118 Maximum Plasma Concentration (Cmax) | 6 ng/mL | — |
| Arm 1 MK-2118 300 μg IT Monotherapy | MK-2118 Maximum Plasma Concentration (Cmax) | 75 ng/mL | — |
| Arm 1 MK-2118 900 μg IT Monotherapy | MK-2118 Maximum Plasma Concentration (Cmax) | 94 ng/mL | — |
| Arm 1 MK-2118 2700 μg IT Monotherapy | MK-2118 Maximum Plasma Concentration (Cmax) | 259 ng/mL | Geometric Coefficient of Variation 168 |
| Arm 1 MK-2118 5400 μg IT Monotherapy | MK-2118 Maximum Plasma Concentration (Cmax) | 685 ng/mL | Geometric Coefficient of Variation 41 |
| Arm 1 MK-2118 7700 μg IT Monotherapy | MK-2118 Maximum Plasma Concentration (Cmax) | 1303 ng/mL | Geometric Coefficient of Variation 57 |
| Arm 1 MK-2118 10000 μg IT Monotherapy | MK-2118 Maximum Plasma Concentration (Cmax) | 1142 ng/mL | Geometric Coefficient of Variation 91 |
| Arm 1 MK-2118 15000 μg IT Monotherapy | MK-2118 Maximum Plasma Concentration (Cmax) | 2329 ng/mL | Geometric Coefficient of Variation 84 |
| Arm 1 MK-2118 20000 μg IT Monotherapy | MK-2118 Maximum Plasma Concentration (Cmax) | 3170 ng/mL | Geometric Coefficient of Variation 47 |
| Arm 2 MK-2118 2700 μg IT + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Maximum Plasma Concentration (Cmax) | 442 ng/mL | Geometric Coefficient of Variation 7 |
| Arm 2 MK-2118 5400 μg IT + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Maximum Plasma Concentration (Cmax) | 348 ng/mL | Geometric Coefficient of Variation 568 |
| Arm 2 MK-2118 7700 μg IT + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Maximum Plasma Concentration (Cmax) | 1091 ng/mL | Geometric Coefficient of Variation 99 |
| Arm 2 MK-2118 10000 μg IT + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Maximum Plasma Concentration (Cmax) | 1715 ng/mL | Geometric Coefficient of Variation 60 |
| Arm 2 MK-2118 15000 μg IT + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Maximum Plasma Concentration (Cmax) | 1758 ng/mL | Geometric Coefficient of Variation 242 |
| Arm 4: MK-2118 5000 μg Subcutaneous (SC) + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Maximum Plasma Concentration (Cmax) | 790 ng/mL | Geometric Coefficient of Variation 21 |
| Arm 4: MK-2118 10000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Maximum Plasma Concentration (Cmax) | 1530 ng/mL | Geometric Coefficient of Variation 40 |
| Arm 4: MK-2118 15000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Maximum Plasma Concentration (Cmax) | 1630 ng/mL | Geometric Coefficient of Variation 112 |
| Arm 4: MK-2118 20000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Maximum Plasma Concentration (Cmax) | 3032 ng/mL | Geometric Coefficient of Variation 26 |
| Arm 4: MK-2118 30000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Maximum Plasma Concentration (Cmax) | 5441 ng/mL | Geometric Coefficient of Variation 36 |
| Arm 4: MK-2118 45000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Maximum Plasma Concentration (Cmax) | 8407 ng/mL | Geometric Coefficient of Variation 17 |
| Arm 4: MK-2118 60000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Maximum Plasma Concentration (Cmax) | 7168 ng/mL | Geometric Coefficient of Variation 117 |
| Arm 4: MK-2118 90000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Maximum Plasma Concentration (Cmax) | 10637 ng/mL | Geometric Coefficient of Variation 35 |
| Arm 4: MK-2118 120000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Maximum Plasma Concentration (Cmax) | 21763 ng/mL | Geometric Coefficient of Variation 63 |
| Arm 4: MK-2118 150000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Maximum Plasma Concentration (Cmax) | 24117 ng/mL | Geometric Coefficient of Variation 20 |
Secondary
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)
Population: The subset of participants who complied with the protocol and had MK-2118 Cmin data available. Per protocol, PK outcomes were not analyzed separately for the switch-over treatment arms.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 MK-2118 100 μg Intra-tumoral (IT) Monotherapy | MK-2118 Minimum Plasma Concentration (Cmin) | 2 ng/mL | — |
| Arm 1 MK-2118 300 μg IT Monotherapy | MK-2118 Minimum Plasma Concentration (Cmin) | 2 ng/mL | — |
| Arm 1 MK-2118 900 μg IT Monotherapy | MK-2118 Minimum Plasma Concentration (Cmin) | 3 ng/mL | — |
| Arm 1 MK-2118 2700 μg IT Monotherapy | MK-2118 Minimum Plasma Concentration (Cmin) | 3 ng/mL | Geometric Coefficient of Variation 17 |
| Arm 1 MK-2118 5400 μg IT Monotherapy | MK-2118 Minimum Plasma Concentration (Cmin) | 7 ng/mL | Geometric Coefficient of Variation 70 |
| Arm 1 MK-2118 7700 μg IT Monotherapy | MK-2118 Minimum Plasma Concentration (Cmin) | 6 ng/mL | Geometric Coefficient of Variation 104 |
| Arm 1 MK-2118 10000 μg IT Monotherapy | MK-2118 Minimum Plasma Concentration (Cmin) | 3 ng/mL | Geometric Coefficient of Variation 90 |
| Arm 1 MK-2118 15000 μg IT Monotherapy | MK-2118 Minimum Plasma Concentration (Cmin) | 8 ng/mL | Geometric Coefficient of Variation 153 |
| Arm 1 MK-2118 20000 μg IT Monotherapy | MK-2118 Minimum Plasma Concentration (Cmin) | 9 ng/mL | Geometric Coefficient of Variation 105 |
| Arm 2 MK-2118 2700 μg IT + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Minimum Plasma Concentration (Cmin) | 7 ng/mL | Geometric Coefficient of Variation 45 |
| Arm 2 MK-2118 5400 μg IT + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Minimum Plasma Concentration (Cmin) | 8 ng/mL | Geometric Coefficient of Variation 99 |
| Arm 2 MK-2118 7700 μg IT + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Minimum Plasma Concentration (Cmin) | 6 ng/mL | Geometric Coefficient of Variation 178 |
| Arm 2 MK-2118 10000 μg IT + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Minimum Plasma Concentration (Cmin) | 9 ng/mL | Geometric Coefficient of Variation 127 |
| Arm 2 MK-2118 15000 μg IT + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Minimum Plasma Concentration (Cmin) | 10 ng/mL | Geometric Coefficient of Variation 228 |
| Arm 4: MK-2118 5000 μg Subcutaneous (SC) + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Minimum Plasma Concentration (Cmin) | 7 ng/mL | Geometric Coefficient of Variation 142 |
| Arm 4: MK-2118 10000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Minimum Plasma Concentration (Cmin) | 7 ng/mL | Geometric Coefficient of Variation 127 |
| Arm 4: MK-2118 15000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Minimum Plasma Concentration (Cmin) | 8 ng/mL | Geometric Coefficient of Variation 168 |
| Arm 4: MK-2118 20000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Minimum Plasma Concentration (Cmin) | 5 ng/mL | Geometric Coefficient of Variation 107 |
| Arm 4: MK-2118 30000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Minimum Plasma Concentration (Cmin) | 7 ng/mL | Geometric Coefficient of Variation 44 |
| Arm 4: MK-2118 45000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Minimum Plasma Concentration (Cmin) | 44 ng/mL | Geometric Coefficient of Variation 3435 |
| Arm 4: MK-2118 60000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Minimum Plasma Concentration (Cmin) | 11 ng/mL | Geometric Coefficient of Variation 216 |
| Arm 4: MK-2118 90000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Minimum Plasma Concentration (Cmin) | 16 ng/mL | Geometric Coefficient of Variation 212 |
| Arm 4: MK-2118 120000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Minimum Plasma Concentration (Cmin) | 36 ng/mL | Geometric Coefficient of Variation 50 |
| Arm 4: MK-2118 150000 μg SC + Pembrolizumab 200 mg IV Combination Therapy | MK-2118 Minimum Plasma Concentration (Cmin) | 32 ng/mL | Geometric Coefficient of Variation 64 |
Secondary
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)
Population: The subset of participants who complied with the protocol and had pembrolizumab Cmin data available. Pembrolizumab Cmin analysis was not planned in Arm 1 (MK-2118 IT monotherapy) or for the switch-over treatment arms, per protocol. For Arm 2 (MK-2118 IT + Pembrolizumab combination) and Arm 4 (MK-2118 SC + Pembrolizumab combination), pembrolizumab Cmin data were not collected.