Gastrointestinal Stromal Tumors
Conditions
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).
Interventions
DRUGRipretinib
50 mg tablets
DRUGbinimetinib
15 mg tablets
Sponsors
Deciphera Pharmaceuticals, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients ≥18 years of age with advanced GIST (unresectable or metastatic). 2. Must have at least progressed on imatinib or have documented intolerance to imatinib. 3. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. 4. Patients must have a histologic diagnosis of GIST. 5. If a female of childbearing potential, must have a negative pregnancy test. 6. Adequate organ function and bone marrow function
Exclusion criteria
1. Received prior anticancer therapy within 14 days or 5× the half-life whichever is longer) prior to the first dose. 2. Ongoing or prior participation in the DCC-2618-03-002 study. 3. Prior therapy with ripretinib. 4. Prior therapy with MEK inhibitor. 5. History of certain ocular disorders. 6. History of clinically significant hepatobiliary disease. 7. Known active central nervous system metastases. 8. History or presence of clinically relevant cardiovascular abnormalities. 9. Systemic arterial or venous thrombotic or embolic events within 6 months of first dose. 10. History of acute or chronic pancreatitis 11. History of chronic inflammatory bowel disease or Crohn's disease requiring intervention within 12 months of first dose. 12. Gastrointestinal abnormalities including but not limited to: * inability to take oral medication, * malabsorption syndromes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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 | Approximately 36 months | Measure ORR |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 progression-free survival (PFS) of ripretinib in combination with binimetinib | Approximately 36 months | Measure PFS |
| 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 |
| Evaluate the duration of response (DOR) of ripretinib in combination with binimetinib | Approximately 36 months | Measure DOR |
| 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 |
| Evaluate the overall survival (OS) of ripretinib in combination with binimetinib | Approximately 36 months | Measure OS |
| 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 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 |
Outcome results
None listed