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

Advanced Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05394350
• Other study ID #: 1088-002
• Secondary ID: MK-1088-0022021-
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: July 7, 2022
• Est. completion date: September 7, 2023

Study information

• Verified date: September 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 27
• Est. completion date: September 7, 2023
• Est. primary completion date: September 7, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 NYHA Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability

• Has a 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

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• MK-1088
Oral Tablet

Biological:
• Pembrolizumab
IV Infusion

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Canada,  Denmark,  Israel,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number 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). Number of participants who experience a DLT will be reported.	Up to 21 days
Primary	Number 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. The number of participants who experienced an AE will be reported.	Up to ~27 months
Primary	Number 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. The number of participants who discontinued study treatment due to an AE will be reported.	Up to ~24 months
Secondary	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 will be reported.	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 ~27 months. Each cycle = 21 days
Secondary	Maximum plasma concentration (Cmax) of MK-1088	Cmax of MK-1088 determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.	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 ~27 months. Each cycle = 21 days
Secondary	Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (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. The percentage of participants who experience a CR or PR as assessed by the investigator based on RECIST 1.1 will be reported.	Up to ~3 years
Secondary	ORR per 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 PCWG-modified RECIST 1.1. The percentage of participants who experience a CR or PR as assessed by the investigator based on PCWG-modified RECIST 1.1 will be reported.	Up to ~3 years

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary