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

NCT06655246 | Recruiting Phase 1 FDA Drug

• 1 other identifier: KO-MEN-015
• Study Type: interventional
• Target: 157
• Locations: 1 country
• Sites: 32

Brief 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.

Conditions

Gastrointestinal Stromal Tumor (GIST); Gastrointestinal Stromal Cancer; Gastrointestinal Stromal Neoplasm; Gastrointestinal Stromal Cell Tumors; Gastrointestinal Stromal Tumor, Malignant

Keywords

Gastrointestinal Stromal Tumor; Gastrointestinal Stromal Cancer; Gastrointestinal Stromal Neoplasm

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (13)

• Recommended Phase 2 Dose Determination and Dose Expansion: CBR

  Up to 2 years following start of treatment with ziftomenib

• Overall Response Rate (ORR)

  Up to 2 years following start of treatment with ziftomenib

• Progression Free Survival (PFS)

  Up to 2 years following start of treatment with ziftomenib

• Duration of Response (DoR)

  Up to 2 years following start of treatment with ziftomenib

• Overall Survival (OS)

  Up to 2 years following start of treatment with ziftomenib

Study Arms (3)

Dose Escalation

EXPERIMENTAL

Ziftomenib plus imatinib

Drug: ziftomenib; Drug: imatinib mesylate

Recommended Phase 2 Dose Determination

EXPERIMENTAL

Ziftomenib plus imatinib

Drug: ziftomenib; Drug: imatinib mesylate

Dose Expansion

EXPERIMENTAL

Ziftomenib plus imatinib

Drug: ziftomenib; Drug: imatinib mesylate

Interventions

ziftomenib DRUG

menin inhibitor

Dose Escalation; Dose Expansion; Recommended Phase 2 Dose Determination

imatinib mesylate DRUG

kinase inhibitor

Also known as: Gleevec

Dose Escalation; Dose Expansion; Recommended Phase 2 Dose Determination

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kura Oncology, Inc.: lead

Study Sites (32)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

RECRUITING

Mayo Clinic Cancer Center

Phoenix, Arizona, 85054, United States

RECRUITING

University of California, San Diego

La Jolla, California, 92093, United States

RECRUITING

University of Southern California

Los Angeles, California, 90033, United States

RECRUITING

University Of California, Irvine

Orange, California, 92868, United States

RECRUITING

Stanford Cancer Institute

Palo Alto, California, 94304, United States

RECRUITING

UCLA Santa Monica Medical Center

Santa Monica, California, 90404, United States

RECRUITING

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

RECRUITING

Sarah Cannon Research Institute

Denver, Colorado, 80220, United States

RECRUITING

Yale University School of Medicine

New Haven, Connecticut, 06511, United States

RECRUITING

Mayo Clinic Cancer Center

Jacksonville, Florida, 32224, United States

RECRUITING

University of Miami

Miami, Florida, 33136, United States

RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

Johns Hopkins University

Baltimore, Maryland, 21287, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Harvard University

Boston, Massachusetts, 02215, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

RECRUITING

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

Oregon Health & Science University

Portland, Oregon, 97239, United States

RECRUITING

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Temple University Health System

Philadelphia, Pennsylvania, 19111, United States

RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

Sarah Cannon Research Institute

Dallas, Texas, 75230, United States

RECRUITING

University of Texas

Houston, Texas, 77030, United States

RECRUITING

University of Texas Health Science Center

San Antonio, Texas, 78229, United States

RECRUITING

University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

Imatinib Mesylate

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

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Central Study Contacts

Kura Medical Information 844-KURAONC

CONTACT

844-587-2662; medinfo@kuraoncology.com

Study Design

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

Study Record Dates

• First Submitted: October 14, 2024
• First Posted: October 23, 2024
• Study Start: March 27, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: February 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (32)