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

Merck Sharp & Dohme (MSD)

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Advanced Solid Tumors

Treatments: Biological: Pembrolizumab; Drug: MK-1088

Study type: Interventional

Funder types: Industry

Identifiers

NCT05394350

2021-006712-93 (EudraCT Number)

MK-1088-002 (Other Identifier)

1088-002

2022-502288-40-00 (Registry Identifier)

Details and patient eligibility

About

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.

Enrollment: 27 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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27 participants in 6 patient groups

MK-1088 100 mg

Experimental group

Description:

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).

Treatment:

Drug: MK-1088

MK-1088 200 mg

Experimental group

Description:

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)

Treatment:

Drug: MK-1088

MK-1088 400 mg

Experimental group

Description:

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)

Treatment:

Drug: MK-1088

MK-1088 600 mg

Experimental group

Description:

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)

Treatment:

Drug: MK-1088

MK-1088 100 mg + Pembrolizumab

Experimental group

Description:

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)

Treatment:

Drug: MK-1088

Biological: Pembrolizumab

MK-1088 200 mg + Pembrolizumab

Experimental group

Description:

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)

Treatment:

Drug: MK-1088

Biological: Pembrolizumab