Study of MK-2118 Administered as Intratumoral Injection as Monotherapy and in Combination With Pembrolizumab (MK-3475) or by Subcutaneous Injection in Combination With Pembrolizumab in the Treatment of Adults With Advanced/Metastatic Solid Tumors or Lymphomas (MK-2118-001)

A Phase 1 Open-label, Multicenter Study of MK-2118 Administered by Intratumoral Injection as Monotherapy and in Combination With Pembrolizumab or by Subcutaneous Injection in Combination With Pembrolizumab for Patients With Advanced/Metastatic Solid Tumors or Lymphomas

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.

Study Overview

• Status: Terminated
• Conditions: Lymphoma; Solid Tumor
• Intervention / Treatment: Biological: Pembrolizumab; Drug: MK-2118 (IT); Drug: MK-2118 (SC)

Detailed Description

Arm 3 did not enroll any participants.

Data for the pembrolizumab Cmin outcome measure were not collected.

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 1

Contacts and Locations

Study Locations

• Israel
  • Ramat-Gan, Israel, 5265601
    • Sheba Medical Center ( Site 0301)
• United States
  • California
    • La Jolla, California, United States, 92093
      • University of California San Diego Moores Cancer Center ( Site 0004)
    • Los Angeles, California, United States, 90095
      • UCLA ( Site 0003)
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago ( Site 0002)
  • New York
    • New York, New York, United States, 10032
      • New York Presbyterian Hospital/Columbia University ( Site 0001)
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Centers ( Site 0007)
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research Center ( Site 0005)
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Centr. ( Site 0006)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

25

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 MK-2118 100 µg Intra-tumoral (IT) Monotherapy; Participants receive 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.	Drug: MK-2118 (IT); IT injection
Experimental: Arm 1 MK-2118 300 µg IT Monotherapy; Participants receive 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.	Drug: MK-2118 (IT); IT injection
Experimental: Arm 1 MK-2118 900 µg IT Monotherapy; Participants receive 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.	Drug: MK-2118 (IT); IT injection
Experimental: Arm 1 MK-2118 2700 µg IT Monotherapy; Participants receive 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.	Drug: MK-2118 (IT); IT injection
Experimental: Arm 1 MK-2118 5400 µg IT Monotherapy; Participants receive 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.	Drug: MK-2118 (IT); IT injection
Experimental: Arm 1 MK-2118 7700 µg IT Monotherapy; Participants receive 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.	Drug: MK-2118 (IT); IT injection
Experimental: Arm 1 MK-2118 10000 µg IT Monotherapy; Participants receive 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.	Drug: MK-2118 (IT); IT injection
Experimental: Arm 1 MK-2118 15000 µg IT Monotherapy; Participants receive 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.	Drug: MK-2118 (IT); IT injection
Experimental: Arm 1 MK-2118 20000 µg IT Monotherapy; Participants receive 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.	Drug: MK-2118 (IT); IT injection
Experimental: Arm 2 MK-2118 2700 µg IT + Pembrolizumab 200 mg IV Combination Therapy; Participants receive 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 receive 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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; Drug: MK-2118 (IT); IT injection
Experimental: Arm 2 MK-2118 5400 µg IT + Pembrolizumab 200 mg IV Combination Therapy; Participants receive 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 receive 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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; Drug: MK-2118 (IT); IT injection
Experimental: Arm 2 MK-2118 7700 µg IT + Pembrolizumab 200 mg IV Combination Therapy; Participants receive 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 receive 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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; Drug: MK-2118 (IT); IT injection
Experimental: Arm 2 MK-2118 10000 µg IT + Pembrolizumab 200 mg IV Combination Therapy; Participants receive 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 receive 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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; Drug: MK-2118 (IT); IT injection
Experimental: Arm 2 MK-2118 15000 µg IT + Pembrolizumab 200 mg IV Combination Therapy; Participants receive 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 receive 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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; Drug: MK-2118 (IT); IT injection
Experimental: (Not Enrolled) Arm 3 MK-2118 Visceral IT + Pembrolizumab 200 mg IV Combination Therapy; Participants receive MK-2118 via IT injection Q1W on Days 1, 8 and 15 of Cycles 1-2 followed by Q3W on Day 1 of Cycle 3 and beyond, for a total of up to ~35 cycles (up to ~2 years) and 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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; Drug: MK-2118 (IT); IT injection
Experimental: Arm 4: MK-2118 5000 µg Subcutaneous (SC) + Pembrolizumab 200 mg IV Combination Therapy; Participants receive 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 Q3W Day 1 of Cycle 5 and beyond, for a total of up to 36 cycles (up to ~2 years) and receive 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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; Drug: MK-2118 (SC); SC injection
Experimental: Arm 4: MK-2118 10000 µg SC + Pembrolizumab 200 mg IV Combination Therapy; Participants receive 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 Q3W Day 1 of Cycle 5 and beyond, for a total of up to 36 cycles (up to ~2 years) and receive 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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; Drug: MK-2118 (SC); SC injection
Experimental: Arm 4: MK-2118 15000 µg SC + Pembrolizumab 200 mg IV Combination Therapy; Participants receive 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 Q3W Day 1 of Cycle 5 and beyond, for a total of up to 36 cycles (up to ~2 years) and receive 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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; Drug: MK-2118 (SC); SC injection
Experimental: Arm 4: MK-2118 20000 µg SC + Pembrolizumab 200 mg IV Combination Therapy; Participants receive 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 Q3W Day 1 of Cycle 5 and beyond, for a total of up to 36 cycles (up to ~2 years) and receive 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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; Drug: MK-2118 (SC); SC injection
Experimental: Arm 4: MK-2118 30000 µg SC + Pembrolizumab 200 mg IV Combination Therapy; Participants receive 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 Q3W Day 1 of Cycle 5 and beyond, for a total of up to 36 cycles (up to ~2 years) and receive 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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; Drug: MK-2118 (SC); SC injection
Experimental: Arm 4: MK-2118 45000 µg SC + Pembrolizumab 200 mg IV Combination Therapy; Participants receive 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 Q3W Day 1 of Cycle 5 and beyond, for a total of up to 36 cycles (up to ~2 years) and receive 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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; Drug: MK-2118 (SC); SC injection
Experimental: Arm 4: MK-2118 60000 µg SC + Pembrolizumab 200 mg IV Combination Therapy; Participants receive 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 Q3W Day 1 of Cycle 5 and beyond, for a total of up to 36 cycles (up to ~2 years) and receive 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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; Drug: MK-2118 (SC); SC injection
Experimental: Arm 4: MK-2118 90000 µg SC + Pembrolizumab 200 mg IV Combination Therapy; Participants receive 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 Q3W Day 1 of Cycle 5 and beyond, for a total of up to 36 cycles (up to ~2 years) and receive 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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; Drug: MK-2118 (SC); SC injection
Experimental: Arm 4: MK-2118 120000 µg SC + Pembrolizumab 200 mg IV Combination Therapy; Participants receive 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 Q3W Day 1 of Cycle 5 and beyond, for a total of up to 36 cycles (up to ~2 years) and receive 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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; Drug: MK-2118 (SC); SC injection
Experimental: Arm 4: MK-2118 150000 µg SC + Pembrolizumab 200 mg IV Combination Therapy; Participants receive 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 Q3W Day 1 of Cycle 5 and beyond, for a total of up to 36 cycles (up to ~2 years) and receive 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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; Drug: MK-2118 (SC); SC injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	Up to ~27 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Luke JJ, Sweis RF, Hecht JR, Schneider R, Stein MN, Golan T, Yap TA, Khilnani A, Huang M, Zhao R, Jemielita T, Patel SP. Intratumoral or Subcutaneous MK-2118, a Noncyclic Dinucleotide STING Agonist, with or without Pembrolizumab, for Advanced or Metastatic Solid Tumors or Lymphomas. Clin Cancer Res. 2025 Apr 1;31(7):1233-1242. doi: 10.1158/1078-0432.CCR-24-2824.

Helpful Links

• Merck Oncology Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2017
• Primary Completion (Actual): February 22, 2023
• Study Completion (Actual): February 22, 2023

Study Registration Dates

• First Submitted: August 9, 2017
• First Submitted That Met QC Criteria: August 11, 2017
• First Posted (Actual): August 15, 2017

Study Record Updates

• Last Update Posted (Actual): July 24, 2025
• Last Update Submitted That Met QC Criteria: July 8, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pembrolizumab
• Other Study ID Numbers: 2118-001; MK-2118-001 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No