Clinical trial NCT05594043: A Study of MK-6598 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Advanced Solid Tumors (MK-6598-001)
Official title: A Phase 1, Open-label, Multicenter Study to Assess Safety, Tolerability, PK, and Efficacy of MK-6598 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced or Metastatic Solid Tumors
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: 2022-10-26
Enrollment: 90
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 assess the efficacy and safety and establish a preliminary recommended Phase 2 dose (RP2D) of MK-6598 administered as monotherapy and in combination with pembrolizumab (MK-3475) in adult participants with advanced or metastatic solid tumors.


Eligibility criteria: Inclusion Criteria:

* Has a histologically- or cytologically-confirmed advanced/metastatic solid tumor by pathology report and has received, or been intolerant to, all treatment known to confer clinical benefit.
* Has measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by the local site investigator/radiology.
* Has one or more discrete malignant lesions that are amenable to a minimum of 2 separate biopsies.
* Has a baseline tumor sample that can be submitted for analysis.
* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART).
* A participant assigned male sex at birth who receives MK-6598 must agree to use contraception and should refrain from donating sperm during the specified period(s) of at least 102 days after study interventions.
* A participant assigned female sex at birth is eligible to participate if not pregnant or breastfeeding and at least 1 of the following: not a participant of childbearing potential (POCBP) or a POCBP who agrees to follow the contraceptive guidance during the treatment period and for up to 120 days after study intervention.

Exclusion Criteria:

* Received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention or has not recovered to CTCAE Version 5.0 Grade 1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier (this includes participants with previous immunomodulatory therapy with residual immune-related AEs).
* Known additional malignancy that is progressing or has required active treatment within 2 years.
* Clinically active central nervous system (CNS) metastases and/or carcinomatous meningitis.
* A severe hypersensitivity (≥Grade 3) reaction to treatment with a monoclonal antibody/components of the study intervention.
* Active infection requiring therapy.
* History of interstitial lung disease.
* History of (noninfectious) pneumonitis that required steroids or current pneumonitis.
* Active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed.
* Has known hepatitis B or C infections or known to be positive for hepatitis B surface antigen (HBsAg)/hepatitis B virus (HBV) deoxyribonucleic acid (DNA) or hepatitis C antibody or ribonucleic acid (RNA).
* Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
* Received prior radiotherapy within 2 weeks of start of study intervention, has radiation-related toxicities requiring corticosteroids, or had a history of radiation pneumonitis.
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 \[CTLA-4\], OX 40, CD137), and was discontinued from that treatment due to a ≥Grade 3 immune-related AE (irAE).
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the start of study treatment.
* Has had an allogeneic tissue/solid organ transplant in the last 5 years or has evidence of graft-versus-host disease.

Primary outcomes:
measure: Number of Participants with a Dose-Limiting Toxicity (DLT) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events (AEs) Version 5.0
timeFrame: Up to approximately 21 days
measure: Number of Participants Who Experience At Least One AE
timeFrame: Up to approximately 27 months
measure: Number of Participants Who Discontinue Study Treatment Due to an AE
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Area Under the Curve (AUC) of MK-6598
timeFrame: Days 1, 8, and 15 of Cycle 1: predose, postdose at 30 minutes (min), 45 min, 60 min, 2 hours (hrs), 6 hrs; Days 2 and 9 of Cycle 1: predose; Day 1 of Cycles 2, 5, 10, 15, 20, 25, 30, and 35: predose
measure: Minimum Serum Concentration (Cmin) of MK-6598
timeFrame: Days 1, 8, and 15 of Cycle 1: predose, postdose at 30 min, 45 min, 60 min, 2 hrs, 6 hrs; Days 2 and 9 of Cycle 1: predose; Day 1 of Cycles 2, 5, 10, 15, 20, 25, 30, and 35: predose
measure: Maximum Serum Concentration (Cmax) of MK-6598
timeFrame: Days 1, 8, and 15 of Cycle 1: predose, postdose at 30 min, 45 min, 60 min, 2 hrs, 6 hrs; Days 2 and 9 of Cycle 1: predose; Day 1 of Cycles 2, 5, 10, 15, 20, 25, 30, and 35: predose
measure: Tumor Phenylpyruvate Concentrations
timeFrame: Days 1, 8, and 15 of Cycle 1: predose, postdose at 30 min, 45 min, 60 min, 2 hrs, 6 hrs; Days 2 and 9 of Cycle 1: predose; Day 1 of Cycles 2, 5, 10, 15, 20, 25, 30, and 35: predose
Other outcomes:
Locations:
city: Sioux Falls
country: United States
facility: Sanford Cancer Center ( Site 0300)
state: South Dakota
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre ( Site 0101)
state: Ontario
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal-Unit for Innovative Therapies ( Site 0100)
state: Quebec
city: Genève
country: Switzerland
facility: Hôpitaux Universitaires de Genève (HUG) ( Site 0202)
state: Geneve
city: Bellinzona
country: Switzerland
facility: Ospedale Regionale Bellinzona e Valli ( Site 0200)
state: Ticino
city: Sankt Gallen
country: Switzerland
facility: Cantonal Hospital St.Gallen ( Site 0203)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: