A Study of MK-1088 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors (MK-1088-002)

A Phase 1/Phase 2 Study to Evaluate the Safety and Tolerability of MK-1088 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors

The study will evaluate the safety, tolerability, and pharmacokinetics (PK) of MK-1088 in monotherapy and in combination with pembrolizumab in participants with advanced solid tumors who have not responded to conventional therapy. The effect of MK-1088 on tumor size will also be examined.

Study Overview

• Status: Terminated
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: MK-1088; Biological: Pembrolizumab

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1J 1Z4
    • Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0201)
• Denmark
  • Hovedstaden
    • Copenhagen, Hovedstaden, Denmark, 2100
      • Rigshospitalet ( Site 0500)
    • Copenhagen, Hovedstaden, Denmark, 2730
      • Herlev and Gentofte Hospital ( Site 0501)
  • Syddanmark
    • Odense, Syddanmark, Denmark, 5000
      • Odense Universitetshospital ( Site 0502)
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus-Oncology Division ( Site 0300)
  • Jerusalem, Israel, 9112001
    • Hadassah Medical Center ( Site 0302)
• Switzerland
  • Grisons
    • Chur, Grisons, Switzerland, 7000
      • Kantonsspital Graubünden-Medizin ( Site 0402)
  • Sankt Gallen
    • st.Gallen, Sankt Gallen, Switzerland, 9007
      • Cantonal Hospital St.Gallen ( Site 0403)
  • Ticino
    • Bellinzona, Ticino, Switzerland, 6500
      • Ospedale Regionale Bellinzona e Valli ( Site 0400)
• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Hospital and Clinics, Sylvester Cancer Center ( Site 0103)
  • New York
    • New York, New York, United States, 10016
      • Laura and Isaac Perlmutter Cancer Center ( Site 0102)
  • Texas
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics (START) ( Site 0101)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

• Has a histologically- or cytologically-confirmed diagnosis of advanced/metastatic solid tumor by pathology report and have received, have been intolerant to, or have been ineligible for treatment known to confer clinical benefit
• For metastatic castrate-resistant prostate cancer (mCRPC) only: (1) Must have previously received docetaxel, prior treatment with one other chemotherapy is allowed as well as up to 2 second-generation hormonal manipulations and (2) have prostate cancer progression within 6 months before screening, as determined by the investigator
• If human immunodeficiency virus (HIV) positive, has well-controlled HIV on anti-retroviral therapy (ART)

Exclusion Criteria:

• Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) before the first dose of study intervention
• Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
• Has clinically active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has an active infection requiring therapy
• Has a history of interstitial lung disease
• Has a history of (noninfectious) pneumonitis that required steroids or current pneumonitis
• Has an active autoimmune disease that has required systemic treatment in the past 2 years
• Has concurrent active Hepatitis B and Hepatitis C virus infection
• Has HIV with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• Has not fully recovered from any effects of major surgery without significant detectable infection
• Has a history or current evidence of a gastrointestinal (GI) condition or impaired liver function or diseases that in the opinion of the investigator may significantly alter the absorption or metabolism of oral medications
• Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Health Association (NYHA) Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability
• Has a corrected QT interval using Fridericia's Correction Formula (QTcF) >470 msec
• Has history of an allogeneic stem cell transplant or a solid organ transplant.
• Has received prior systemic anticancer therapy including investigational agents within 4 weeks before allocation
• Has received prior radiotherapy within 2 weeks of start of study intervention, or had radiation-related toxicities requiring corticosteroids
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
• Has a "superscan" bone scan

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MK-1088 100 mg; Participants received MK-1088 daily (QD) orally at 100 mg on days 1-21 of each 21-day cycle for up to 35 cycles (up to ~24 months).	Drug: MK-1088; Oral Tablet
Experimental: MK-1088 200 mg; Participants received MK-1088 (QD) orally at 200 mg on days 1-21 of each 21-day cycle for up to 35 cycles (up to ~24 months)	Drug: MK-1088; Oral Tablet
Experimental: MK-1088 400 mg; Participants received MK-1088 (QD) orally at 400 mg on days 1-21 of each 21-day cycle for up to 35 cycles (up to ~24 months)	Drug: MK-1088; Oral Tablet
Experimental: MK-1088 600 mg; Participants received MK-1088 (QD) orally at 600 mg on days 1-21 of each 21-day cycle for up to 35 cycles (up to ~24 months)	Drug: MK-1088; Oral Tablet
Experimental: MK-1088 100 mg + Pembrolizumab; Participants received MK-1088 daily (QD) orally at 100 mg on days 1-21 of each 21-day cycle plus pembrolizumab at 200 mg intravenous (IV) infusion every 3 weeks (Q3W), on Day 1 of each 21-day cycle for up to 35 cycles (up to ~24 months)	Drug: MK-1088; Oral Tablet; Biological: Pembrolizumab; IV Infusion; Other Names: MK-3475; KEYTRUDA®
Experimental: MK-1088 200 mg + Pembrolizumab; Participants received MK-1088 daily (QD) orally at 200 mg on days 1-21 of each 21-day cycle plus pembrolizumab at 200 mg intravenous (IV) infusion every 3 weeks (Q3W), on Day 1 of each 21-day cycle for up to 35 cycles (up to ~24 months)	Drug: MK-1088; Oral Tablet; Biological: Pembrolizumab; IV Infusion; Other Names: MK-3475; KEYTRUDA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Experiencing a Dose-limiting Toxicity (DLT)	A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0). Per protocol participants who switched over from MK-1088 monotherapy into MK-1088 100 mg + Pembrolizumab combination therapy completed the DLT evaluation period in the monotherapy arm assigned. Percentage of participants who experienced a DLT are presented.	Up to 21 days
Percentage of Participants Experiencing an Adverse Event (AE)	An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. Safety data from participants who experienced disease progression in the monotherapy arm and crossed over into the combination arm are summarized in their initial monotherapy dose group until the time of cross over and are summarized separately thereafter. The percentage of participants who experienced an AE are presented.	Up to ~13 months
Percentage of Participants Discontinuing Study Treatment Due to an AE	An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. Safety data from participants who experienced disease progression in the monotherapy arm and crossed over into the combination arm are summarized in their initial monotherapy dose group until the time of cross over and are summarized separately thereafter. The percentage of participants who discontinued study treatment due to an AE is presented.	Up to ~10 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-time Curve (AUC) of MK-1088	AUC of MK-1088 determined by blood samples collected pre-dose and at designated timepoints post-dose are presented.	Pre-dose and 1, 2, 4, and 8 hours post-dose on Cycle 1 Day 1 and Cycle 2 Day 1; Pre-dose on Cycle 1 Day 2 and Cycle 2 Day 2; Pre-dose on Cycle 3, Cycle 4 and every 4 cycles up to ~3.5 months. Each cycle = 21 days
Maximum Plasma Concentration (Cmax) of MK-1088	Cmax of MK-1088 determined by blood samples collected pre-dose and at designated timepoints post-dose are presented.	Pre-dose and 1, 2, 4, and 8 hours post-dose on Cycle 1 Day 1 and Cycle 2 Day 1; Pre-dose on Cycle 1 Day 2 and Cycle 2 Day 2; Pre-dose on Cycle 3, Cycle 4 and every 4 cycles up to ~3.5 months. Each cycle = 21 days
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) or Prostate Cancer Working Group (PCWG)-Modified RECIST 1.1 as Assessed by Investigator	ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 or Prostate Cancer Working Group (PCWG)-modified RECIST 1.1 as assessed by investigator. Efficacy data from participants who experienced disease progression in the monotherapy arm and crossed over into the combination arm will be summarized in their initial monotherapy dose group until the time of cross over and will be summarized separately thereafter. The percentage of participants who experience a CR or PR as assessed by the investigator based on RECIST 1.1 is presented.	Up to ~13 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2022
• Primary Completion (Actual): September 7, 2023
• Study Completion (Actual): September 7, 2023

Study Registration Dates

• First Submitted: May 23, 2022
• First Submitted That Met QC Criteria: May 23, 2022
• First Posted (Actual): May 27, 2022

Study Record Updates

• Last Update Posted (Estimated): November 8, 2024
• Last Update Submitted That Met QC Criteria: November 7, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pembrolizumab
• Other Study ID Numbers: 1088-002; MK-1088-002 (Other Identifier: Merck); 2021-006712-93 (EudraCT Number); 2022-502288-40-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No