RecruitingInterventionalPhase 1

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

NCT ID: NCT06655246Sponsor: Kura Oncology, Inc.Last updated: 2026-02-05

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.

Arms & interventions

Drugziftomenib
menin inhibitor
Drugimatinib mesylate
kinase inhibitor

Outcome measures

Primary

Dose Escalation: Dose Limiting Toxicity (DLT)
Rate of DLTs per dose level
Time frame: 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
Time frame: 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
Time frame: Up to 2 years following start of treatment with ziftomenib

Secondary

Recommended Phase 2 Dose Determination and Dose Expansion: CBR
Time frame: Up to 2 years following start of treatment with ziftomenib
Overall Response Rate (ORR)
Time frame: Up to 2 years following start of treatment with ziftomenib
Progression Free Survival (PFS)
Time frame: Up to 2 years following start of treatment with ziftomenib
Duration of Response (DoR)
Time frame: Up to 2 years following start of treatment with ziftomenib
Overall Survival (OS)
Time frame: Up to 2 years following start of treatment with ziftomenib
Maximum plasma concentration (Cmax)
Time frame: Day 1 of each cycle; each cycle is 28 days
Time to maximum plasma concentration (Tmax)
Time frame: 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)
Time frame: Day 1 of each cycle; each cycle is 28 days
Area under the concentration-time curve over a dosing interval (AUC tau)
Time frame: Day 1 of each cycle; each cycle is 28 days
Maximum plasma concentration (Cmax)
Time frame: Day 1 of each cycle; each cycle is 28 days
Time to maximum plasma concentration (Tmax)
Time frame: 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)
Time frame: Day 1 of each cycle; each cycle is 28 days
Area under the concentration-time curve over a dosing interval (AUC tau)
Time frame: Day 1 of each cycle; each cycle is 28 days

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy 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.

Study locations (32)

University of Alabama at Birmingham

Birmingham, Alabama, 35233

Recruiting

Mayo Clinic Cancer Center

Phoenix, Arizona, 85054

Recruiting

University of California, San Diego

La Jolla, California, 92093

Recruiting

University of Southern California

Los Angeles, California, 90033

Recruiting

University Of California, Irvine

Orange, California, 92868

Recruiting

Stanford Cancer Institute

Palo Alto, California, 94304

Recruiting

UCLA Santa Monica Medical Center

Santa Monica, California, 90404

Recruiting

University of Colorado Cancer Center

Aurora, Colorado, 80045

Recruiting

Sarah Cannon Research Institute

Denver, Colorado, 80220

Recruiting

Yale University School of Medicine

New Haven, Connecticut, 06511

Recruiting

Mayo Clinic Cancer Center

Jacksonville, Florida, 32224

Recruiting

University of Miami

Miami, Florida, 33136

Recruiting

Northwestern University

Chicago, Illinois, 60611

Recruiting

University of Iowa

Iowa City, Iowa, 52242

Recruiting

Johns Hopkins University

Baltimore, Maryland, 21287

Recruiting

Massachusetts General Hospital

Boston, Massachusetts, 02114

Recruiting

Harvard University

Boston, Massachusetts, 02215

Recruiting

University of Michigan

Ann Arbor, Michigan, 48109

Recruiting

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905

Recruiting

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065

Recruiting

Duke University Medical Center

Durham, North Carolina, 27710

Recruiting

Ohio State University

Columbus, Ohio, 43210

Recruiting

Oregon Health & Science University

Portland, Oregon, 97239

Recruiting

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107

Recruiting

Temple University Health System

Philadelphia, Pennsylvania, 19111

Recruiting

Sarah Cannon Research Institute

Nashville, Tennessee, 37203

Recruiting

Vanderbilt University Medical Center

Nashville, Tennessee, 37232

Recruiting

Sarah Cannon Research Institute

Dallas, Texas, 75230

Recruiting

University of Texas

Houston, Texas, 77030

Recruiting

University of Texas Health Science Center

San Antonio, Texas, 78229

Recruiting

University of Utah

Salt Lake City, Utah, 84112

Recruiting

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226

Recruiting