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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Advanced or Metastatic Solid Tumors

Treatments: Drug: MK-6598; Biological: Pembrolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05594043

6598-001

MK-6598-001 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 90 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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90 participants in 2 patient groups

MK-6598

Experimental group

Description:

Participants will receive MK-6598 daily (QD) at escalating dose levels from 50-500 mg for up to a total of 35 cycles (up to approximately 24 months).

Treatment:

Drug: MK-6598

MK-6598 + Pembrolizumab

Experimental group

Description:

Participants will receive MK-6598 QD at escalating dose levels from 50-500, plus pembrolizumab 200 mg once every 21-day cycle for up to 35 cycles (up to approximately 24 months).

Treatment:

Biological: Pembrolizumab

Drug: MK-6598