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

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)

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 Overview

• Status: Withdrawn
• Conditions: Gastrointestinal Stromal Tumors
• Intervention / Treatment: Drug: Ripretinib; Drug: binimetinib

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Escalation; 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	Drug: Ripretinib; 50 mg tablets; Other Names: DCC-2618, QINLOCK; Drug: binimetinib; 15 mg tablets; Other Names: Mektovi
Experimental: Expansion; 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	Drug: Ripretinib; 50 mg tablets; Other Names: DCC-2618, QINLOCK; Drug: binimetinib; 15 mg tablets; Other Names: Mektovi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Deciphera Pharmaceuticals LLC

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2021
• Primary Completion (Anticipated): November 1, 2025
• Study Completion (Anticipated): May 1, 2027

Study Registration Dates

• First Submitted: September 20, 2021
• First Submitted That Met QC Criteria: October 4, 2021
• First Posted (Actual): October 18, 2021

Study Record Updates

• Last Update Posted (Actual): January 5, 2022
• Last Update Submitted That Met QC Criteria: December 15, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors
• Other Study ID Numbers: DCC-2618-01-008

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No