A Study of the Safety, Tolerability, and Efficacy of MK-8353 in Participants With Advanced Solid Tumors (MK-8353-001)

Study Overview
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Brief Summary
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This study of the safety, tolerability, and efficacy of MK-8353 (formerly SCH 900353) given as single agent oral therapy for participants with advanced solid tumors will be done into two parts. In Part 1a, there will be a dose escalation to find the preliminary maximum tolerated dose (MTD), and in Part 1b, dose confirmation to find out the recommended Phase 2 dose (RPTD) that will be used in Part 2 of the study. In Part 2 of the study, participants with certain types of metastatic melanoma or metastatic colorectal cancer will be treated to see if MK-8353 is effective as single agent therapy.

Official Title
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A Phase 1 Study to Evaluate the Safety, Tolerability and Efficacy of MK-8353 (Formerly SCH 900353) in Subjects With Advanced Solid Tumors (Protocol No. 001 (Formerly P06203))

Conditions
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Tumor, Solid

Intervention / Treatment
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* Drug: MK-8353


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically/histologically confirmed solid tumor (metastatic or locally advanced disease) that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist. Participants of childbearing potential must have negative pregnancy test; females and males must agree to use effective contraception during the course of the trial and for 90 days after stopping study drug. For Part 1b and Part 2, participant with metastatic melanoma or metastatic colorectal cancer with at least one measurable lesion Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with a life expectancy of ≥3 months. Adequate organ function. Exclusion Criteria: Unstable or progressing central nervous system (CNS) metastasis unless asymptomatic for 3 months, with no need for steroids or antiseizure medications. Active gastrointestinal disease or a disorder or a history of surgery that significantly alters gastrointestinal motility or absorption. Has not recovered from previous therapy and had any chemotherapy, biologic, or hormonal therapy within 4 weeks of study enrollment. Radiation therapy (except palliative radiation to bone lesions) within 4 weeks of study enrollment. More than 3 prior regimens of chemotherapy, biologic therapy, hormonal therapy, or investigational drugs not including adjuvant or neoadjuvant treatments. Clinically relevant cardiovascular, hepatic, neurologic, endocrine, or other major systemic diseases. Mean QTcF interval (interval on the electrocardiogram corrected for heart rate using Fridericia's correction) > 450 msec at baseline. Known Human Immunodeficiency Virus (HIV) infection, hepatitis infection, or tuberculosis infection. Current participation in any other interventional clinical study. History of significant eye disease, including glaucoma, retinopathy, or retinal vein occlusion.

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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-8353 100 mg twice daily (BID)<br>100 mg capsules administered orally twice daily for 28 days for each cycle | Drug: MK-8353<br>* Administered orally twice daily for 28 days for each cycle<br>|
| Experimental: MK-8353 200 mg BID<br>200 mg capsules administered orally twice daily for 28 days for each cycle | Drug: MK-8353<br>* Administered orally twice daily for 28 days for each cycle<br>|
| Experimental: MK-6353 300 mg BID<br>300 mg capsules administered orally twice daily for 28 days for each cycle | Drug: MK-8353<br>* Administered orally twice daily for 28 days for each cycle<br>|
| Experimental: MK-8353 350 mg BID<br>350 mg capsules administered orally twice daily for 28 days for each cycle | Drug: MK-8353<br>* Administered orally twice daily for 28 days for each cycle<br>|
| Experimental: MK-8353 400 mg BID<br>400 mg capsules administered orally twice daily for 28 days for each cycle | Drug: MK-8353<br>* Administered orally twice daily for 28 days for each cycle<br>|
| Experimental: MK-8353 800 mg BID<br>800 mg capsules administered orally twice daily for 28 days for each cycle | Drug: MK-8353<br>* Administered orally twice daily for 28 days for each cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose-Limiting Toxicities (DLTs) | DLT was derived from the toxicities observed during the first cycle (28 days) for each dose level. DLT is defined as any hematologic or non-hematologic toxicity ≥Grade 3 as pre-specified per protocol, or drug-related toxicity, regardless of Common Terminology Criteria for Adverse Events (CTCAE) grade that causes >20% of the intended total number of doses in Cycle 1 to be missed. | Cycles of 28 days, up to approximately 9 months treatment and a 30-day follow-up period for a total time of up to approximately 10 months | 
| Number of Participants With Overall Response Rate | Overall Response rate is defined as the number of participants who had a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. | Baseline, and every 8 weeks until disease progression or discontinuation from study up to approximately 10 months |