A Study of Ziftomenib in Combination With Imatinib in Patients With Advanced Gastrointestinal Stromal Tumors (GIST)

NCT06655246
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Phase
Phase 1
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Recruitment status
Recruiting
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Participants
157
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Lead sponsor
Kura Oncology, Inc.
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Start date
2025-03-27
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Number of sites
32
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Summary
In this clinical trial, the safety, tolerability, and preliminary antitumor activity of ziftomenib in combination with imatinib will be evaluated in adults with gastrointestinal stromal tumors (GIST) who have been treated previously with imatinib.
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Short title
A Study of Ziftomenib in Combination With Imatinib in Patients With Advanced Gastrointestinal Stromal Tumors (GIST)
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Official title
A Phase 1a/1b Study of the Safety, Pharmacokinetics, and Antitumor Activity of the Oral Menin Inhibitor Ziftomenib in Combination With Imatinib in Patients With Advanced Gastrointestinal Stromal Tumors (GIST) After Imatinib Failure
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2028-12-01
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First posted
2024-10-23
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Registry last updated
2026-02-05
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Primary completion date
2027-12-01
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Start date
2025-03-27
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Participants
157
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Participant count basis
Estimated
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Planned participants
157
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Protocol amendments
2
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Number of sites
32
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
Kura Oncology, Inc.
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06655246
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ClinicalTrials.gov ID
NCT06655246
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Registry record
Open registry record
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Allocation
Not randomised
Model
Single group
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Dose Escalation: Dose Limiting Toxicity (DLT)

    Timeframe: Cycle 1 (first 28 day cycle)

    Rate of DLTs per dose level

  2. Descriptive statistics of Adverse Events (AEs)

    Timeframe: First dose of ziftomenib up to and including 28 days after last dose of ziftomenib, or if the participant is lost to follow-up, whichever comes first

    Per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0

  3. Dose Expansion: Clinical benefit rate (CBR)

    Timeframe: Up to 2 years following start of treatment with ziftomenib

    CBR is the rate of participants achieving complete response (CR), partial response (PR), or stable disease (SD), assessed per Response Criteria in Solid Tumors (RECIST) v1.1 modified for GIST

  1. Recommended Phase 2 Dose Determination and Dose Expansion: CBR

    Timeframe: Up to 2 years following start of treatment with ziftomenib

    CBR is CR + PR + SD assessed per RECIST v1.1 modified for GIST

  2. Overall Response Rate (ORR)

    Timeframe: Up to 2 years following start of treatment with ziftomenib

    ORR is CR + PR assessed per RECIST v1.1 modified for GIST

  3. Progression Free Survival (PFS)

    Timeframe: Up to 2 years following start of treatment with ziftomenib

    Assessed per RECIST v1.1 modified for GIST

  4. Duration of Response (DoR)

    Timeframe: Up to 2 years following start of treatment with ziftomenib

    Defined as the time from the first response (CR or PR assessed per RECIST v1.1 modified for GIST) to disease progression or death from any cause

  5. Overall Survival (OS)

    Timeframe: Up to 2 years following start of treatment with ziftomenib

    Defined as the time from first dose of ziftomenib or imatinib (whichever is dosed first) until death from any cause

  6. Maximum plasma concentration (Cmax)

    Timeframe: Day 1 of each cycle; each cycle is 28 days

    Cmax of ziftomenib

  7. Time to maximum plasma concentration (Tmax)

    Timeframe: Day 1 of each cycle; each cycle is 28 days

    Tmax of ziftomenib

  8. Area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC 0-last)

    Timeframe: Day 1 of each cycle; each cycle is 28 days

    AUC 0-last of ziftomenib

  9. Area under the concentration-time curve over a dosing interval (AUC tau)

    Timeframe: Day 1 of each cycle; each cycle is 28 days

    AUC tau of ziftomenib

  10. Maximum plasma concentration (Cmax)

    Timeframe: Day 1 of each cycle; each cycle is 28 days

    Cmax of imatinib

  11. Time to maximum plasma concentration (Tmax)

    Timeframe: Day 1 of each cycle; each cycle is 28 days

    Tmax of imatinib

  12. Area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC 0-last)

    Timeframe: Day 1 of each cycle; each cycle is 28 days

    AUC 0-last of imatinib

  13. Area under the concentration-time curve over a dosing interval (AUC tau)

    Timeframe: Day 1 of each cycle; each cycle is 28 days

    AUC tau of imatinib

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

Key Inclusion Criteria:

  • Documented diagnosis of advanced/metastatic KIT-mutant GIST.
  • Documented disease progression on imatinib as current or prior therapy.
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 at screening.
  • At least 1 measurable lesion per RECIST v1.1 modified for GIST.
  • Negative pregnancy test for participants of childbearing potential.
  • Adequate organ function per protocol requirements.
  • Resolution of all clinically significant toxicities from prior therapy to <Grade 1 (or participant baseline) within 1 week before the first dose of study intervention.
  • Participant, or legally authorized representative, must be able to understand and provide written informed consent before the first screening procedure.

Key Exclusion Criteria:

  • Diagnosis of GIST without a KIT mutation or with a T670X KIT mutation.
  • History of prior or current cancer that has potential to interfere with obtaining study results.
  • Received a prohibited medication, including investigational therapy, less than 14 days or within 5 drug half-lives before the first dose of study intervention.
  • Active central nervous system metastases.
  • Uncontrolled intercurrent illness, including, but not limited to protocol defined cardiac disease.
  • Mean corrected QT interval (QTcF) greater than 470ms.
  • Left ventricular ejection fraction (LVEF) <50%.
  • Major surgery within 2 weeks before the first dose of study intervention.
  • Is pregnant or breastfeeding.
  • Gastrointestinal abnormalities that may impact taking study intervention by mouth.
  • Actively bleeding, excluding hemorrhoidal or gum bleeding.
Sources for eligibility
clinicaltrials.gov

  • University of Alabama at BirminghamBirmingham, United StatesRecruiting
  • Mayo Clinic Cancer CenterPhoenix, United StatesRecruiting
  • University of California, San DiegoLa Jolla, United StatesRecruiting
  • University of Southern CaliforniaLos Angeles, United StatesRecruiting
  • University Of California, IrvineOrange, United StatesRecruiting
  • Stanford Cancer InstitutePalo Alto, United StatesRecruiting
  • UCLA Santa Monica Medical CenterSanta Monica, United StatesRecruiting
  • University of Colorado Cancer CenterAurora, United StatesRecruiting
  • Sarah Cannon Research InstituteDenver, United StatesRecruiting
  • Yale University School of MedicineNew Haven, United StatesRecruiting
  • Mayo Clinic Cancer CenterJacksonville, United StatesRecruiting
  • University of MiamiMiami, United StatesRecruiting
  • Northwestern UniversityChicago, United StatesRecruiting
  • University of IowaIowa City, United StatesRecruiting
  • Johns Hopkins UniversityBaltimore, United StatesRecruiting
  • Massachusetts General HospitalBoston, United StatesRecruiting
  • Harvard UniversityBoston, United StatesRecruiting
  • University of MichiganAnn Arbor, United StatesRecruiting
  • Mayo Clinic Cancer CenterRochester, United StatesRecruiting
  • Memorial Sloan-Kettering Cancer CenterNew York, United StatesRecruiting
  • Duke University Medical CenterDurham, United StatesRecruiting
  • Ohio State UniversityColumbus, United StatesRecruiting
  • Oregon Health & Science UniversityPortland, United StatesRecruiting
  • Thomas Jefferson UniversityPhiladelphia, United StatesRecruiting
  • Temple University Health SystemPhiladelphia, United StatesRecruiting

And 7 more, listed on the interactive page.

Sources for sites
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Related records

Drugs (2)

Lead sponsors (1)

Conditions (1)

Targets (4)