Clinical trial NCT06460961: A Study of MK-6837 as a Monotherapy and Combination Therapy in Participants With Advanced/Metastatic Solid Tumors (MK-6837-001)
Official title: A Phase 1 Open-label, Multicenter Study of MK-6837 as Monotherapy and Combination Therapy in Participants With Advanced/Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Neoplasm Metastasis
Keywords: Programmed Cell Death-1 (PD1, PD-1)
Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1)
Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2024-06-14
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Number of participants who experience one or more dose-limiting toxicities (DLTs)
timeFrame: Cycle 1 (Up to approximately 21 days); each cycle is 21 days.
measure: Number of participants who experience one or more adverse events (AEs)
timeFrame: Up to approximately 59 months
measure: Number of participants who discontinue study intervention due to an AE
timeFrame: Up to approximately 59 months
Secondary outcomes:
measure: Maximum concentration (Cmax) of MK-6837 in plasma
timeFrame: 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
measure: Minimum concentration (Ctrough) of MK-6837 in plasma
timeFrame: 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
measure: Area Under the Concentration-Time Curve (AUC) of MK-6837 in plasma
timeFrame: 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
Other outcomes:
Locations:
city: Morristown
country: United States
facility: Atlantic Health System Morristown Medical Center ( Site 4001)
state: New Jersey
city: Portland
country: United States
facility: Providence Portland Medical Center ( Site 4002)
state: Oregon
city: Westmead
country: Australia
facility: Westmead Hospital ( Site 1002)
state: New South Wales
city: Melbourne
country: Australia
facility: The Alfred Hospital ( Site 1001)
state: Victoria
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre ( Site 2001)
state: Ontario
city: Ramat Gan
country: Israel
facility: Sheba Medical Center-ONCOLOGY ( Site 3001)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: