A Study of MK-6598 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Advanced Solid Tumors (MK-6598-001)

Advanced or Metastatic Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05594043
• Other study ID #: 6598-001
• Secondary ID: MK-6598-001
• Status: Recruiting
• Phase: Phase 1
• Start date: December 21, 2022
• Est. completion date: December 13, 2027

Study information

• Verified date: August 2023
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: December 13, 2027
• Est. primary completion date: December 13, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced or Metastatic Solid Tumors
• Neoplasms

Intervention

Drug:
• MK-6598
Oral tablet

Biological:
• Pembrolizumab
Intravenous (IV) infusion

Locations

Country	Name	City	State
Canada	Centre Hospitalier de l'Université de Montréal-Unit for Innovative Therapies ( Site 0100)	Montréal	Quebec
Canada	Princess Margaret Cancer Centre ( Site 0101)	Toronto	Ontario
Switzerland	Ospedale Regionale Bellinzona e Valli ( Site 0200)	Bellinzona	Ticino
Switzerland	Hôpitaux Universitaires de Genève (HUG) ( Site 0202)	Genève	Geneve
Switzerland	Cantonal Hospital St.Gallen ( Site 0203)	Sankt Gallen
United States	Sanford Cancer Center ( Site 0300)	Sioux Falls	South Dakota

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Canada,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with a Dose-Limiting Toxicity (DLT) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events (AEs) Version 5.0	DLT is defined as any of the following toxicities, unless assessed by the investigator to be clearly due to the underlying disease or extraneous causes: Grade (Gr) 4 nonhematologic toxicity (not laboratory); Gr 4 hematologic toxicity lasting =7 days, except thrombocytopenia; Gr 4 thrombocytopenia of any duration; Gr 3 thrombocytopenia associated with clinically significant bleeding; Gr 4 anemia regardless of duration; Nonhematologic AE Gr =3 in severity, with exceptions; Any Gr 3 or 4 nonhematologic lab abnormality if clinically significant medical intervention is required, or if leads to hospitalization, persists for >72 hours or results in drug-induced liver injury with exceptions; Gr 3 or 4 febrile neutropenia; Prolonged delay (>2 weeks) in initiating Cycle 2 due to treatment-related toxicity; Treatment-related toxicity resulting in study treatment discontinuation during Cycle 1 (C1); Missing >25% of MK-6598 doses as a result of treatment-related AE during C1; Gr 5 toxicity.	Up to approximately 21 days
Primary	Number of Participants Who Experience At Least One AE	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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE will be reported.	Up to approximately 27 months
Primary	Number of Participants Who Discontinue Study Treatment Due to an AE	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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued study treatment due to an AE will be reported.	Up to approximately 24 months
Secondary	Area Under the Curve (AUC) of MK-6598	Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine AUC.	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
Secondary	Minimum Serum Concentration (Cmin) of MK-6598	Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmin	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
Secondary	Maximum Serum Concentration (Cmax) of MK-6598	Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmax.	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
Secondary	Tumor Phenylpyruvate Concentrations	Blood samples pre-dose and at multiple timepoints post-dose will be used to determine tumor phenylpyruvate concentrations.	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

External Links

•   Merck Clinical Trials Information