Ripretinib in Combination With Binimetinib in Patients With Gastrointestinal Stromal Tumor (GIST)
- Conditions
- Gastrointestinal Stromal Tumors
- Interventions
- Registration Number
- NCT05080621
- Lead Sponsor
- Deciphera Pharmaceuticals, LLC
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- Patients ≥18 years of age with advanced GIST (unresectable or metastatic).
- Must have at least progressed on imatinib or have documented intolerance to imatinib.
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
- Patients must have a histologic diagnosis of GIST.
- If a female of childbearing potential, must have a negative pregnancy test.
- Adequate organ function and bone marrow function
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Received prior anticancer therapy within 14 days or 5× the half-life whichever is longer) prior to the first dose.
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Ongoing or prior participation in the DCC-2618-03-002 study.
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Prior therapy with ripretinib.
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Prior therapy with MEK inhibitor.
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History of certain ocular disorders.
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History of clinically significant hepatobiliary disease.
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Known active central nervous system metastases.
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History or presence of clinically relevant cardiovascular abnormalities.
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Systemic arterial or venous thrombotic or embolic events within 6 months of first dose.
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History of acute or chronic pancreatitis
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History of chronic inflammatory bowel disease or Crohn's disease requiring intervention within 12 months of first dose.
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Gastrointestinal abnormalities including but not limited to:
- inability to take oral medication,
- malabsorption syndromes
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Expansion Ripretinib Ripretinib in combination with binimetinib at the recommended Phase 2 dose (RP2D) in patients with advanced GIST who have progressed on imatinib or are intolerant to imatinib and are naïve. Participants may remain on treatment until disease progression, unacceptable toxicity, or withdrawal of consent Escalation Ripretinib Escalation Phase: Increasing doses of ripretinib in combination with increase doses of binimetinib in patients with advanced GIST who have progressed on at least imatinib or are intolerant to imatinib and are ripretinib naïve in repeated 28-day cycles. Participants may remain on treatment until disease progression, unacceptable toxicity, or withdrawal of consent Expansion binimetinib Ripretinib in combination with binimetinib at the recommended Phase 2 dose (RP2D) in patients with advanced GIST who have progressed on imatinib or are intolerant to imatinib and are naïve. Participants may remain on treatment until disease progression, unacceptable toxicity, or withdrawal of consent Escalation binimetinib Escalation Phase: Increasing doses of ripretinib in combination with increase doses of binimetinib in patients with advanced GIST who have progressed on at least imatinib or are intolerant to imatinib and are ripretinib naïve in repeated 28-day cycles. Participants may remain on treatment until disease progression, unacceptable toxicity, or withdrawal of consent
- Primary Outcome Measures
Name Time Method Determination of the Maximum Tolerated Dose and the Recommended Phase 2 Dose Approximately 12 months Safety/tolerability of oral ripretinib in combination with binimetinib: incidence of adverse events Approximately 12 months 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).
Expansion Phase Only: Evaluate the objective response rate (ORR) of ripretinib in combination with binimetinib by modified RECIST Approximately 36 months Measure ORR
- Secondary Outcome Measures
Name Time Method Determine the minimum observed concentration (Cmin) profile of oral ripretinib in combination with binimetinib 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 Measure Cmin
Evaluate the progression-free survival (PFS) of ripretinib in combination with binimetinib Approximately 36 months Measure PFS
Evaluate the duration of response (DOR) of ripretinib in combination with binimetinib Approximately 36 months Measure DOR
Determine the time to maximum observed concentration (tmax) profile of oral ripretinib in combination with binimetinib 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 Measure Tmax
Determine the maximum observed concentration (Cmax) profile of oral ripretinib in combination with binimetinib 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 Measure Cmax
Determine the area under the concentration-time curve (AUC) profile of oral ripretinib in combination with binimetinib 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 Measure AUC
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) Approximately 36 months Measure ORR
Evaluate the overall survival (OS) of ripretinib in combination with binimetinib Approximately 36 months Measure OS
Evaluate the clinical benefit rate (CBR) of ripretinib in combination with binimetinib Approximately 36 months Measure CBR
Evaluate the time to response (TTR) of ripretinib in combination with binimetinib Approximately 36 months Measure TTR