Study of MK-0472 in Participants With Advanced/Metastatic Solid Tumors (MK-0472-001)
Study Details
Study Description
Brief Summary
The purpose of this study is to assess the efficacy, safety, and tolerability of MK-0472 administered as monotherapy and in combination with pembrolizumab (MK-3475) in participants with histologically or cytologically confirmed diagnosis of advanced/metastatic solid tumors.
There is no primary hypothesis to be tested for this study.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: MK-0472 Participants receive MK-0472 capsule up to 300 mg orally once daily (QD) until disease progression or withdrawal/discontinuation. |
Drug: MK-0472
Oral Administration
|
| Experimental: MK-0472+Pembrolizumab Participants receive MK-0472 capsule up to 300 mg orally QD until disease progression or withdrawal/discontinuation plus Pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years). |
Drug: MK-0472
Oral Administration
Biological: Pembrolizumab
IV infusion
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants Who Experience a Dose Limiting Toxicity (DLT) as Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 [At the end of Cycle 1 (each cycle is 21 days)]
DLT will be defined as any drug-related AE observed during the DLT evaluation period (e.g. Cycle 1) that results in a change to a given dose or a delay in initiating the next cycle.
- Number of Participants Who Experience One or More Adverse Events (AEs) [Up to approximately 56 months]
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who experience one or more AE's will be reported.
- Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) [Up to approximately 56 months]
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who discontinue study treatment due to an AE will be reported.
Secondary Outcome Measures
- Area Under the Concentration Time-curve From Time 0 to the Last Quantifiable Concentration (AUC0-t) of MK-0472 [Cycle 1 Day 1; Cycle 2 Day 1: Predose and 1, 2, 4, and 8 hours postdose; Cycles 1, 2: Days 2, 15: Predose (Each cycle length = 21 days)]
Blood samples will be collected at specified intervals for the determination of AUC0-t. AUC0-t is defined as the area under concentration-time curve from 0 to last quantifiable concentration.
- Lowest Plasma Concentration (Ctrough) of MK-0472 [Cycles 2-6, and every third cycle up to Cycle 81: Day 1: Predose (Each cycle length = 21 days)]
Blood samples will be collected at specified intervals for the determination of Ctrough. Ctrough is defined as the lowest concentration of MK-0472 reached before the next dose is administered.
- Maximum Serum Concentration (Cmax) of MK-0472 [Cycle 1 Day 1; Cycle 2 Day 1: 1, 2, 4, and 8 hours postdose (Each cycle length = 21 days)]
Blood samples will be collected at specified intervals for the determination of Cmax. Cmax is defined as the maximum concentration of MK-0472 reached.
Eligibility Criteria
Criteria
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
- Histologically or cytologically confirmed unresectable advanced/metastatic solid tumor by pathology report with oncogenically activated receptor tyrosine kinase (RTK) confirmed by a historical report or local testing and have received, or been intolerant to, all available treatment known to confer clinical benefit
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
-
Has not recovered to common terminology criteria for adverse events (CTCAE) Grade 1 or better from any adverse events that were due to cancer therapeutics administered more than 4 weeks earlier. Participants receiving ongoing replacement hormone therapy for endocrine immune-related AEs will not be excluded from participation in this study
-
Has history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
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History of hyperparathyroidism or hypercalcemia
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Has one or more of the following ophthalmological findings/conditions: a) Intraocular pressure >21 mm Hg and/or any diagnosis of glaucoma b) Diagnosis of central serous retinopathy, retinal vein occlusion, or retinal artery occlusion and c) Diagnosis of retinal degenerative disease
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Has clinically significant cardiovascular disease
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Bullous exfoliative skin disorders of any grade
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Known hypersensitivity to MK-0472 or pembrolizumab, or any of their excipients
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Received therapy with a proton-pump inhibitor or an H2 histamine blocker receptor antagonist within 7 days before the first scheduled day of study dosing
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Has discontinued prior therapy with an anti-programmed cell death-1 (PD-1), anti-programmed death-ligand 1 (PD-L1), or anti-programmed death-ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor due to an adverse event
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Received prior systemic anticancer therapy including investigational agents within 4 weeks before first dose
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Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
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Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
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Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication
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Has known additional malignancy that is progressing or has required active treatment within the past 2 years
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Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable for at least 4 weeks as confirmed by repeat imaging performed during the study screening, are clinically stable and have not required steroid treatment for at least 14 days before the first dose of study intervention
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Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy
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Has history of pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
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Has active infection requiring systemic therapy
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Has history of human immunodeficiency virus (HIV) infection
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Has known history of Hepatitis B or known active Hepatitis C virus infection
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Has history of allogeneic tissue/solid organ transplant
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Have not adequately recovered from major surgery or have ongoing surgical complications
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 0472-001
- MK-0472-001