A Study of MK-6837 as a Monotherapy and Combination Therapy in Participants With Advanced/Metastatic Solid Tumors (MK-6837-001)
- Conditions
- Neoplasm Metastasis
- Interventions
- Registration Number
- NCT06460961
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of MK-6837, administered as a monotherapy and in combination with pembrolizumab (MK-3475), in participants with histologically or cytologically confirmed advanced/metastatic solid tumors that have not responded to conventional therapy. There will not be any hypothesis testing in the study.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 100
The main inclusion criteria include but are not limited to the following:
- Histologically or cytologically confirmed solid tumor by pathology report that is advanced or metastatic
- Human Immunodeficiency Virus (HIV)-infected participants must have well controlled HIV on Antiretroviral Therapy (ART)
- Participants who are Hepatitis B Surface Antigen (HBsAg) positive are eligible if they have received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load before allocation
- Participants with history of Hepatitis C Virus (HCV) infection are eligible if HCV viral load is undetectable at screening
The main exclusion criteria include but are not limited to the following:
- Has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from any Adverse Events (AEs) that were due to cancer therapeutics administered more than 4 weeks earlier
- History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
- Has clinically significant cardiovascular disease
- HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- Received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention
- Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher immune-related AE (except endocrine disorders that can be treated with replacement therapy) or was discontinued from that treatment due to Grade 2 myocarditis or recurrent Grade 2 pneumonitis
- Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
- Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed
- Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of study intervention
- Known additional malignancy that is progressing or has required active treatment within the past 2 years
- Known active Central Nervous System (CNS) metastases and/or carcinomatous meningitis
- Active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy
- History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- Active infection requiring systemic therapy
- History of allogeneic tissue/solid organ transplant
- Participants who have not adequately recovered from major surgery or have ongoing surgical complications
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1: MK-6837 Monotherapy MK-6837 Participants receive escalating doses of MK-6837 via intravenous (IV) infusion once every 3 weeks (Q3W) (Day 1 of every 21-day cycle) until progressive disease or discontinuation. Arm 2: MK-6837 + Pembrolizumab Combination Therapy MK-6837 Participants receive escalating doses of MK-6837 via IV infusion Q3W (Day 1 of every 21-day cycle) until progressive disease or discontinuation PLUS 200mg of pembrolizumab via IV infusion Q3W (Day 1 of every 21-day cycle) for up to 35 administrations (up to \~2 years). Arm 2: MK-6837 + Pembrolizumab Combination Therapy Pembrolizumab Participants receive escalating doses of MK-6837 via IV infusion Q3W (Day 1 of every 21-day cycle) until progressive disease or discontinuation PLUS 200mg of pembrolizumab via IV infusion Q3W (Day 1 of every 21-day cycle) for up to 35 administrations (up to \~2 years).
- Primary Outcome Measures
Name Time Method Number of participants who experience one or more adverse events (AEs) Up to approximately 59 months An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Number of participants who discontinue study intervention due to an AE Up to approximately 59 months An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Number of participants who experience one or more dose-limiting toxicities (DLTs) Cycle 1 (Up to approximately 21 days); each cycle is 21 days. The following events will be considered a DLT unless clearly due to underlying disease or extraneous causes: Grade 4 neutropenia lasting \>7 days; Grade 3 or higher thrombocytopenia associated with clinically significant bleeding, regardless of duration; All Grade 3 or higher nonhematologic toxicities (with exceptions); Any abnormality that results in a drug induced liver injury; Febrile neutropenia Grade 3 or 4; Prolonged delay (\>2 weeks) in initiating treatment after the first 21 days due to intervention-related toxicity; Any intervention-related toxicity that causes the participant to discontinue intervention during the first 21 days; Grade 5 toxicity. The number of participants who experience a DLT will be presented.
- Secondary Outcome Measures
Name Time Method Area Under the Concentration-Time Curve (AUC) of MK-6837 in plasma Day 1 of cycles 1 and 4: Predose, ~30 minutes, 1, 2, and 4 hours postdose and once daily on Days 2, 3, 5, 8, 11, and 15 postdose; Cycles 2, 3, 5, 6, and every 6 cycles thereafter (up to ~59 months): predose and ~30 minutes postdose; each cycle is 21 days The AUC of MK-6837 in plasma will be determined.
Maximum concentration (Cmax) of MK-6837 in plasma Day 1 of cycles 1 and 4: Predose, ~30 minutes, 1, 2, and 4 hours postdose and once daily on Days 2, 3, 5, 8, 11, and 15 postdose; Cycles 2, 3, 5, 6, and every 6 cycles thereafter (up to ~59 months): predose and ~30 minutes postdose; each cycle is 21 days The Cmax of MK-6837 in plasma will be determined.
Minimum concentration (Ctrough) of MK-6837 in plasma Day 1 of cycles 1 and 4: Predose, ~30 minutes, 1, 2, and 4 hours postdose and once daily on Days 2, 3, 5, 8, 11, and 15 postdose; Cycles 2, 3, 5, 6, and every 6 cycles thereafter (up to ~59 months): predose and ~30 minutes postdose; each cycle is 21 days The Ctrough of MK-6837 in plasma will be determined.
Trial Locations
- Locations (6)
Atlantic Health System Morristown Medical Center ( Site 4001)
🇺🇸Morristown, New Jersey, United States
Providence Portland Medical Center ( Site 4002)
🇺🇸Portland, Oregon, United States
Westmead Hospital ( Site 1002)
🇦🇺Westmead, New South Wales, Australia
The Alfred Hospital ( Site 1001)
🇦🇺Melbourne, Victoria, Australia
Princess Margaret Cancer Centre ( Site 2001)
🇨🇦Toronto, Ontario, Canada
Sheba Medical Center-ONCOLOGY ( Site 3001)
🇮🇱Ramat Gan, Israel