Ripretinib in Combination With Binimetinib in Patients With Gastrointestinal Stromal Tumor (GIST)

Gastrointestinal Stromal Tumors Clinical Trial

Official title:

A Phase 1b/2, Open-label, Multicenter Study to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of Ripretinib in Combination With Binimetinib in Patients With Gastrointestinal Stromal Tumor (GIST)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05080621
• Other study ID #: DCC-2618-01-008
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: November 2021
• Est. completion date: May 2027

Study information

• Verified date: December 2021
• Source: Deciphera Pharmaceuticals LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: May 2027
• Est. primary completion date: November 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Gastrointestinal Stromal Tumors

Intervention

Drug:
• Ripretinib
50 mg tablets
• binimetinib
15 mg tablets

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Deciphera Pharmaceuticals LLC

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Determination of the Maximum Tolerated Dose and the Recommended Phase 2 Dose		Approximately 12 months
Primary	Expansion Phase Only: Evaluate the objective response rate (ORR) of ripretinib in combination with binimetinib by modified RECIST	Measure ORR	Approximately 36 months
Secondary	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
Secondary	Determine the maximum observed concentration (Cmax) profile of oral ripretinib in combination with binimetinib	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Evaluate the progression-free survival (PFS) of ripretinib in combination with binimetinib	Measure PFS	Approximately 36 months
Secondary	Evaluate the overall survival (OS) of ripretinib in combination with binimetinib	Measure OS	Approximately 36 months
Secondary	Evaluate the duration of response (DOR) of ripretinib in combination with binimetinib	Measure DOR	Approximately 36 months
Secondary	Evaluate the clinical benefit rate (CBR) of ripretinib in combination with binimetinib	Measure CBR	Approximately 36 months
Secondary	Evaluate the time to response (TTR) of ripretinib in combination with binimetinib	Measure TTR	Approximately 36 months