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

NCT05080621 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: DCC-2618-01-008
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Gastrointestinal Stromal Tumors

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (10)

• 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

• 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

• 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

• 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

• 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

Study Arms (2)

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

Drug: Ripretinib; Drug: binimetinib

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

Drug: Ripretinib; Drug: binimetinib

Interventions

Ripretinib DRUG

50 mg tablets

Also known as: DCC-2618, QINLOCK

Escalation; Expansion

binimetinib DRUG

15 mg tablets

Also known as: Mektovi

Escalation; Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• inability to take oral medication,
• malabsorption syndromes

Sponsors & Collaborators

• Deciphera Pharmaceuticals, LLC: lead

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

ripretinib; binimetinib

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2021
• First Posted: October 18, 2021
• Study Start: November 1, 2021
• Primary Completion: November 1, 2025
• Study Completion (Estimated): May 1, 2027
• Last Updated: January 5, 2022

Record last verified: 2021-12