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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: MK-1088
* Biological: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-1088<br>Participants will receive MK-1088 daily (QD) orally at specified dose on days 1-21 of each 21-day cycle for up to 35 cycles (up to  24 months). | Drug: MK-1088<br>* Oral Tablet<br>|
| Experimental: MK-1088 + Pembrolizumab<br>Participants will receive MK-1088 daily (QD) orally at specified dose 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<br>* Oral Tablet<br>Biological: Pembrolizumab<br>* IV Infusion<br>* Other names: KEYTRUDA®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 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 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 | 
| 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 | 
| 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 | 
| 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 |