Multicenter, open-label Phase 1b/2 study of ripretinib in combination with binimetinib in patients with gastrointestinal stromal tumor (GIST). There will be 2 distinct parts in this study: Dose Escalation (Phase 1) and Expansion (Phase 2).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
50 mg tablets
15 mg tablets
Safety/tolerability of oral ripretinib in combination with binimetinib: incidence of adverse events
Adverse events \[TEAEs, SAEs, AESIs\], dose reduction, dose interruption, or discontinuation, vital signs (heart rate \[beats/min\], and changes in laboratory parameters (chemistry, hematology, urinalysis, coagulation).
Time frame: Approximately 12 months
Determination of the Maximum Tolerated Dose and the Recommended Phase 2 Dose
Time frame: Approximately 12 months
Expansion Phase Only: Evaluate the objective response rate (ORR) of ripretinib in combination with binimetinib by modified RECIST
Measure ORR
Time frame: Approximately 36 months
Determine the time to maximum observed concentration (tmax) profile of oral ripretinib in combination with binimetinib
Measure Tmax
Time frame: Cycle 1 Day 1, and Cycle 1 Day15 (pre-dose and at multiple time points [up to 8 hours] post-dose). Each cycle is 28 days
Determine the maximum observed concentration (Cmax) profile of oral ripretinib in combination with binimetinib
Measure Cmax
Time frame: Cycle 1 Day 1, and Cycle 1 Day15 (pre-dose and at multiple time points [up to 8 hours] post-dose). Each cycle is 28 days
Determine the minimum observed concentration (Cmin) profile of oral ripretinib in combination with binimetinib
Measure Cmin
Time frame: Cycle 1 Day 1, and Cycle 1 Day15 (pre-dose and at multiple time points [up to 8 hours] post-dose). Each cycle is 28 days
Determine the area under the concentration-time curve (AUC) profile of oral ripretinib in combination with binimetinib
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Measure AUC
Time frame: Cycle 1 Day 1, and Cycle 1 Day15 (pre-dose and at multiple time points [up to 8 hours] post-dose). Each cycle is 28 days
Evaluate the objective response rate (ORR) of ripretinib in combination with binimetinib by modified RECIST (escalation phase only) and Choi criteria (escalation and expansion phases)
Measure ORR
Time frame: Approximately 36 months
Evaluate the progression-free survival (PFS) of ripretinib in combination with binimetinib
Measure PFS
Time frame: Approximately 36 months
Evaluate the overall survival (OS) of ripretinib in combination with binimetinib
Measure OS
Time frame: Approximately 36 months
Evaluate the duration of response (DOR) of ripretinib in combination with binimetinib
Measure DOR
Time frame: Approximately 36 months
Evaluate the clinical benefit rate (CBR) of ripretinib in combination with binimetinib
Measure CBR
Time frame: Approximately 36 months
Evaluate the time to response (TTR) of ripretinib in combination with binimetinib
Measure TTR
Time frame: Approximately 36 months