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

Sponsor
Deciphera Pharmaceuticals LLC (Industry)
Overall Status
Withdrawn
CT.gov ID
NCT05080621
Collaborator
(none)
0
2
65.9

Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
0 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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)
Anticipated Study Start Date :
Nov 1, 2021
Anticipated Primary Completion Date :
Nov 1, 2025
Anticipated Study Completion Date :
May 1, 2027

Arms and Interventions

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
  • Outcome Measures

    Primary Outcome Measures

    1. 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).

    2. Determination of the Maximum Tolerated Dose and the Recommended Phase 2 Dose [Approximately 12 months]

    3. Expansion Phase Only: Evaluate the objective response rate (ORR) of ripretinib in combination with binimetinib by modified RECIST [Approximately 36 months]

      Measure ORR

    Secondary Outcome Measures

    1. 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

    2. 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

    3. 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

    4. 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

    5. 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

    6. Evaluate the progression-free survival (PFS) of ripretinib in combination with binimetinib [Approximately 36 months]

      Measure PFS

    7. Evaluate the overall survival (OS) of ripretinib in combination with binimetinib [Approximately 36 months]

      Measure OS

    8. Evaluate the duration of response (DOR) of ripretinib in combination with binimetinib [Approximately 36 months]

      Measure DOR

    9. Evaluate the clinical benefit rate (CBR) of ripretinib in combination with binimetinib [Approximately 36 months]

      Measure CBR

    10. Evaluate the time to response (TTR) of ripretinib in combination with binimetinib [Approximately 36 months]

      Measure TTR

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Deciphera Pharmaceuticals LLC

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Deciphera Pharmaceuticals LLC
    ClinicalTrials.gov Identifier:
    NCT05080621
    Other Study ID Numbers:
    • DCC-2618-01-008
    First Posted:
    Oct 18, 2021
    Last Update Posted:
    Jan 5, 2022
    Last Verified:
    Dec 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jan 5, 2022