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

NCT05394350 | Terminated Phase 1 Results FDA Drug

• 4 other identifiers: 1088-002MK-1088-0022022-502288-40-002021-006712-93
• Study Type: interventional
• Target: 27
• Locations: 5 countries
• Sites: 13

Brief Summary

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.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (3)

• Area Under the Plasma Concentration-time Curve (AUC) of MK-1088

  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

  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

  Up to ~13 months

Study Arms (6)

MK-1088 100 mg

EXPERIMENTAL

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

MK-1088 200 mg

EXPERIMENTAL

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

MK-1088 400 mg

EXPERIMENTAL

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

MK-1088 600 mg

EXPERIMENTAL

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

MK-1088 100 mg + Pembrolizumab

EXPERIMENTAL

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; Biological: Pembrolizumab

MK-1088 200 mg + Pembrolizumab

EXPERIMENTAL

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; Biological: Pembrolizumab

Interventions

MK-1088 DRUG

Oral Tablet

MK-1088 100 mg; MK-1088 100 mg + Pembrolizumab; MK-1088 200 mg; MK-1088 200 mg + Pembrolizumab; MK-1088 400 mg; MK-1088 600 mg

Pembrolizumab BIOLOGICAL

IV Infusion

Also known as: MK-3475, KEYTRUDA®

MK-1088 100 mg + Pembrolizumab; MK-1088 200 mg + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (13)

University of Miami Hospital and Clinics, Sylvester Cancer Center ( Site 0103)

Miami, Florida, 33136, United States

Location

Laura and Isaac Perlmutter Cancer Center ( Site 0102)

New York, New York, 10016, United States

Location

South Texas Accelerated Research Therapeutics (START) ( Site 0101)

San Antonio, Texas, 78229, United States

Location

Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0201)

Toronto, Ontario, M5G 2M9, Canada

Location

Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0

Québec, Quebec, G1J 1Z4, Canada

Location

Rigshospitalet ( Site 0500)

Copenhagen, Capital Region, 2100, Denmark

Location

Herlev and Gentofte Hospital ( Site 0501)

Copenhagen, Capital Region, 2730, Denmark

Location

Odense Universitetshospital ( Site 0502)

Odense, Region Syddanmark, 5000, Denmark

Location

Rambam Health Care Campus-Oncology Division ( Site 0300)

Haifa, 3109601, Israel

Location

Hadassah Medical Center ( Site 0302)

Jerusalem, 9112001, Israel

Location

Cantonal Hospital St.Gallen ( Site 0403)

Sankt Gallen, Canton of St. Gallen, 9007, Switzerland

Location

Ospedale Regionale Bellinzona e Valli ( Site 0400)

Bellinzona, Canton Ticino, 6500, Switzerland

Location

Kantonsspital Graubünden-Medizin ( Site 0402)

Chur, Kanton Graubünden, 7000, Switzerland

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Interventions

pembrolizumab

Limitations and Caveats

The decision to close study enrollment was based on review of data from the dose escalation phase and Sponsor prioritization. The decision to stop enrollment was not due to any safety concerns, and there were no safety signals observed during the study.

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2022
• First Posted: May 27, 2022
• Study Start: July 7, 2022
• Primary Completion: September 7, 2023
• Study Completion: September 7, 2023
• Last Updated: November 8, 2024
• Results First Posted: October 4, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share

Locations

IL (2); CH (3); CA (2); DK (3); US (3)