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The Sponsor decided to discontinue this study due to a corporate restructuring intended to prioritize clinical development of select programs. No patients enrolled in this study and no patients received investigational product.
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Escalation | Experimental | 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 |
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| Expansion | Experimental | 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 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ripretinib | Drug | 50 mg tablets |
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| Measure | Description | Time Frame |
|---|---|---|
| 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). | Approximately 12 months |
| Determination of the Maximum Tolerated Dose and the Recommended Phase 2 Dose | Approximately 12 months | |
| Expansion Phase Only: Evaluate the objective response rate (ORR) of ripretinib in combination with binimetinib by modified RECIST | Measure ORR | Approximately 36 months |
| Measure | Description | Time Frame |
|---|---|---|
| Determine the time to maximum observed concentration (tmax) profile of oral ripretinib in combination with binimetinib | Measure Tmax | 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 |
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Inclusion Criteria:
Exclusion Criteria:
Received prior anticancer therapy within 14 days or 5× the half-life whichever is longer) prior to the first dose.
Ongoing or prior participation in the DCC-2618-03-002 study.
Prior therapy with ripretinib.
Prior therapy with MEK inhibitor.
History of certain ocular disorders.
History of clinically significant hepatobiliary disease.
Known active central nervous system metastases.
History or presence of clinically relevant cardiovascular abnormalities.
Systemic arterial or venous thrombotic or embolic events within 6 months of first dose.
History of acute or chronic pancreatitis
History of chronic inflammatory bowel disease or Crohn's disease requiring intervention within 12 months of first dose.
Gastrointestinal abnormalities including but not limited to:
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| ID | Term |
|---|---|
| D046152 | Gastrointestinal Stromal Tumors |
| ID | Term |
|---|---|
| D009372 | Neoplasms, Connective Tissue |
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C000707850 | ripretinib |
| C581313 | binimetinib |
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| binimetinib | Drug | 15 mg tablets |
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Measure Cmax |
| 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 | 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 | Measure AUC | 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 | Approximately 36 months |
| Evaluate the progression-free survival (PFS) of ripretinib in combination with binimetinib | Measure PFS | Approximately 36 months |
| Evaluate the overall survival (OS) of ripretinib in combination with binimetinib | Measure OS | Approximately 36 months |
| Evaluate the duration of response (DOR) of ripretinib in combination with binimetinib | Measure DOR | Approximately 36 months |
| Evaluate the clinical benefit rate (CBR) of ripretinib in combination with binimetinib | Measure CBR | Approximately 36 months |
| Evaluate the time to response (TTR) of ripretinib in combination with binimetinib | Measure TTR | Approximately 36 months |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |