This is an open-label, Phase 1, dose escalation study of oral ARQ 736 administered to subjects with advanced solid tumors harboring the mutation. The study is designed to explore the safety, tolerability, pharmacokinetics and pharmacodynamics of ARQ 736 and to define a recommended Phase 2 dose of ARQ 736.
Treatment will be initiated at a dose level of 450 mg twice daily (900 mg/daily). All cycles/cohorts of therapy will consist of the oral administration of ARQ 736 twice or four times a day, one hour prior to or two hours after the meal for 28 days continuously. Tumor assessments (CT scan or MRI) will be performed at Baseline, and every two cycles (every eight weeks) thereafter or as otherwise clinically indicated. For early assessment of evidence of biological activity of the tumor PET scan may be performed at Baseline and four weeks from the administration of the first dose of ARQ 736 (approximately Cycle 2 Day1).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Subjects in this study will receive ARQ 736 orally at dose levels specified for their respective dose cohorts. Dosing will begin at 900 mg/day (first cohort) and escalate until the recommended Phase 2 dose or maximum tolerated dose is determined. Cycles will be repeated in four-week (28-day) intervals until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. In the case of toxicity, dose adjustment will be permitted.
Unnamed facility
Los Angeles, California, United States
Unnamed facility
New Haven, Connecticut, United States
Unnamed facility
New Brunswick, New Jersey, United States
Unnamed facility
Rozzano, Italy
Assess safety and tolerability of study drug in subjects with advanced solid tumors who have BRAF and/or NRAS mutations
Time frame: Up to treatment discontinuation + 30 days with an estimated treatment duration of 24 weeks
Assess pharmacokinetic profile
Time frame: During first cycle of treatment (28 days)
Assess pharmacodynamic activity
Time frame: During first cycle of treatment (28 days) plus Day 1 of each consecutive cycle with an estimated treatment duration of 24 weeks
Determine preliminary evidence of activity
Time frame: Up to treatment discontinuation with an estimated treatment duration of 24 weeks
Determine recommended Phase 2 dose
Time frame: Up to treatment discontinuation with an estimated treatment duration of 24 weeks
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