A Study of Ziftomenib, an Oral Menin Inhibitor, in Combination With Imatinib in Patients With Advanced Gastrointestinal Stromal Tumors (GIST)

Phase 1

Recruiting

• Conditions: Gastrointestinal Stromal Tumor (GIST); Gastrointestinal Stromal Tumor (GIST) of the Gastrointestinal Tract; Gastrointestinal Stromal Cancer; Gastrointestinal Stromal Neoplasm; Gastrointestinal Stromal Tumor, Malignant; Gastrointestinal Stromal Cell Tumors
• Interventions: Drug: ziftomenib; Drug: imatinib mesylate

• Registration Number: NCT06655246
• Lead Sponsor: Kura Oncology, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-10-14
• Study First Submitted QC: 2024-10-22
• Study First Posted: 2024-10-23
• Status Verified: 2025-04
• Study Start: 2025-04
• Last Update Submitted: 2025-04-15
• Last Update Posted: 2025-04-18
• Primary Completion: 2027-12
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 157

Inclusion Criteria

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

Key

Exclusion Criteria

• Diagnosis of non-KIT mutation or a T670X KIT mutation-driven GIST.
• History of prior or currently has cancer which 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 prior to 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 prior to the first dose of study intervention.
• Is pregnant or lactating.
• Gastrointestinal abnormalities that may impact taking study intervention by mouth.
• Actively bleeding, excluding hemorrhoidal or gum bleeding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dose Escalation	ziftomenib	-
Dose Escalation	imatinib mesylate	-
Recommended Phase 2 Dose Determination	ziftomenib	-
Recommended Phase 2 Dose Determination	imatinib mesylate	-
Dose Expansion	ziftomenib	-
Dose Expansion	imatinib mesylate	-

Primary Outcome Measures

Name	Time	Method
Dose Escalation	Cycle 1 (first 28 day cycle)	Rate of Dose Limiting Toxicity per dose level
Dose Escalation, Recommended Phase 2 Dose Determination, Dose Expansion	First dose of ziftomenib up to and including 28 days after last dose of ziftomenib, or if the patient is lost to follow-up, whichever comes first	Descriptive statistics of Adverse Events per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0
Recommended Phase 2 Dose Determination	Up to 1 year of treatment with ziftomenib	Recommended phase 2 dose based on totality of evidence (eg, PK, safety, pharmacodynamics, and preliminary antitumor activity)
Dose Expansion	Up to 1 year following end of treatment with ziftomenib	Rate of patients achieving complete response (CR), partial response (PR), or stable disease (SD) based on modified Response Criteria in Solid Tumors (mRECIST) criteria

Secondary Outcome Measures

Name	Time	Method
Dose Expansion, Recommended Phase 2 Dose Determination, and Dose Expansion: mRECIST Criteria	Up to 1 year following end of treatment with ziftomenib	Overall Survival
Dose Expansion, Recommended Phase 2 Dose Determination, and Dose Expansion: Pharmacokinetics of ziftomenib	Each 28 day cycle	Area under the concentration-time curve over a dosing interval (AUC tau)
Dose Expansion, Recommended Phase 2 Dose Determination, and Dose Expansion: Pharmacokinetics of imatinib	Each 28 day cycle	Area under the concentration-time curve over a dosing interval (AUC tau)

Trial Locations

Locations (2)

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States