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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Gastrointestinal Stromal Tumor (GIST); Gastrointestinal Stromal Neoplasm; Gastrointestinal Stromal Tumor, Malignant; Gastrointestinal Stromal Cancer; Gastrointestinal Stromal Cell Tumors
• Intervention / Treatment: Drug: ziftomenib; Drug: imatinib mesylate

• Study Type: Interventional
• Enrollment (Estimated): 157
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Kura Medical Information 844-KURAONC; Phone Number: 844-587-2662; Email: medinfo@kuraoncology.com

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Recruiting
      • Mayo Clinic Cancer Center
  • California
    • La Jolla, California, United States, 92093
      • Recruiting
      • University of California, San Diego
    • Los Angeles, California, United States, 90033
      • Recruiting
      • University of Southern California
    • Orange, California, United States, 92868
      • Recruiting
      • University of California, Irvine
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford Cancer Institute
    • Santa Monica, California, United States, 90404
      • Recruiting
      • UCLA Santa Monica Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Cancer Center
    • Denver, Colorado, United States, 80220
      • Recruiting
      • Sarah Cannon Research Institute
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Recruiting
      • Yale University School of Medicine
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic Cancer Center
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Harvard University
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic Cancer Center
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan-Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University
    • Philadelphia, Pennsylvania, United States, 19111
      • Recruiting
      • Temple University Health System
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Institute
  • Texas
    • Dallas, Texas, United States, 75230
      • Recruiting
      • Sarah Cannon Research Institute
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • University of Texas Health Science Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Recruiting
      • University of Utah
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; Ziftomenib plus imatinib	Drug: ziftomenib; menin inhibitor; Drug: imatinib mesylate; kinase inhibitor; Other Names: Gleevec
Experimental: Recommended Phase 2 Dose Determination; Ziftomenib plus imatinib	Drug: ziftomenib; menin inhibitor; Drug: imatinib mesylate; kinase inhibitor; Other Names: Gleevec
Experimental: Dose Expansion; Ziftomenib plus imatinib	Drug: ziftomenib; menin inhibitor; Drug: imatinib mesylate; kinase inhibitor; Other Names: Gleevec

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation: Dose Limiting Toxicity (DLT)	Rate of DLTs per dose level	Cycle 1 (first 28 day cycle)
Descriptive statistics of Adverse Events (AEs)	Per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0	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
Dose Expansion: Clinical benefit rate (CBR)	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	Up to 2 years following start of treatment with ziftomenib

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recommended Phase 2 Dose Determination and Dose Expansion: CBR	CBR is CR + PR + SD assessed per RECIST v1.1 modified for GIST	Up to 2 years following start of treatment with ziftomenib
Overall Response Rate (ORR)	ORR is CR + PR assessed per RECIST v1.1 modified for GIST	Up to 2 years following start of treatment with ziftomenib
Progression Free Survival (PFS)	Assessed per RECIST v1.1 modified for GIST	Up to 2 years following start of treatment with ziftomenib
Duration of Response (DoR)	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	Up to 2 years following start of treatment with ziftomenib
Overall Survival (OS)	Defined as the time from first dose of ziftomenib or imatinib (whichever is dosed first) until death from any cause	Up to 2 years following start of treatment with ziftomenib
Maximum plasma concentration (Cmax)	Cmax of ziftomenib	Day 1 of each cycle; each cycle is 28 days
Time to maximum plasma concentration (Tmax)	Tmax of ziftomenib	Day 1 of each cycle; each cycle is 28 days
Area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC 0-last)	AUC 0-last of ziftomenib	Day 1 of each cycle; each cycle is 28 days
Area under the concentration-time curve over a dosing interval (AUC tau)	AUC tau of ziftomenib	Day 1 of each cycle; each cycle is 28 days
Maximum plasma concentration (Cmax)	Cmax of imatinib	Day 1 of each cycle; each cycle is 28 days
Time to maximum plasma concentration (Tmax)	Tmax of imatinib	Day 1 of each cycle; each cycle is 28 days
Area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC 0-last)	AUC 0-last of imatinib	Day 1 of each cycle; each cycle is 28 days
Area under the concentration-time curve over a dosing interval (AUC tau)	AUC tau of imatinib	Day 1 of each cycle; each cycle is 28 days

Collaborators and Investigators

• Sponsor: Kura Oncology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: October 14, 2024
• First Submitted That Met QC Criteria: October 22, 2024
• First Posted (Actual): October 23, 2024

Study Record Updates

• Last Update Posted (Actual): February 5, 2026
• Last Update Submitted That Met QC Criteria: February 3, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Gastrointestinal Stromal Tumor; Gastrointestinal Stromal Cancer; Gastrointestinal Stromal Neoplasm
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Hydrocarbons, Cyclic; Carboxylic Acids; Hydrocarbons, Aromatic; Amides; Pyrimidines; Benzene Derivatives; Acids, Carbocyclic; Benzoates; Benzamides; Piperazines; Imatinib Mesylate
• Other Study ID Numbers: KO-MEN-015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No