Clinical trial NCT06655246: A Study of Ziftomenib, an Oral Menin Inhibitor, in Combination With Imatinib in Patients With Advanced Gastrointestinal Stromal Tumors (GIST)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
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
Keywords: Gastrointestinal Stromal Tumor
Gastrointestinal Stromal Cancer
Gastrointestinal Stromal Neoplasm
Lead sponsor: Kura Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2024-10-23
Enrollment: 157
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Key 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.

Primary outcomes:
measure: Dose Escalation
timeFrame: Cycle 1 (first 28 day cycle)
measure: Dose Escalation, Recommended Phase 2 Dose Determination, Dose Expansion
timeFrame: 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
measure: Recommended Phase 2 Dose Determination
timeFrame: Up to 1 year of treatment with ziftomenib
measure: Dose Expansion
timeFrame: Up to 1 year following end of treatment with ziftomenib
Secondary outcomes:
measure: Dose Expansion, Recommended Phase 2 Dose Determination, and Dose Expansion: mRECIST Criteria
timeFrame: Up to 1 year following end of treatment with ziftomenib
measure: Dose Expansion, Recommended Phase 2 Dose Determination, and Dose Expansion: mRECIST Criteria
timeFrame: Up to 1 year following end of treatment with ziftomenib
measure: Dose Expansion, Recommended Phase 2 Dose Determination, and Dose Expansion: mRECIST Criteria
timeFrame: Up to 1 year following end of treatment with ziftomenib
measure: Dose Expansion, Recommended Phase 2 Dose Determination, and Dose Expansion: mRECIST Criteria
timeFrame: Up to 1 year following end of treatment with ziftomenib
measure: Dose Expansion, Recommended Phase 2 Dose Determination, and Dose Expansion: mRECIST Criteria
timeFrame: Up to 1 year following end of treatment with ziftomenib
measure: Dose Expansion, Recommended Phase 2 Dose Determination, and Dose Expansion: Pharmacokinetics of ziftomenib
timeFrame: Each 28 day cycle
measure: Dose Expansion, Recommended Phase 2 Dose Determination, and Dose Expansion: Pharmacokinetics of ziftomenib
timeFrame: Each 28 day cycle
measure: Dose Expansion, Recommended Phase 2 Dose Determination, and Dose Expansion: Pharmacokinetics of ziftomenib
timeFrame: Each 28 day cycle
measure: Dose Expansion, Recommended Phase 2 Dose Determination, and Dose Expansion: Pharmacokinetics of ziftomenib
timeFrame: Each 28 day cycle
measure: Dose Expansion, Recommended Phase 2 Dose Determination, and Dose Expansion: Pharmacokinetics of imatinib
timeFrame: Each 28 day cycle
measure: Dose Expansion, Recommended Phase 2 Dose Determination, and Dose Expansion: Pharmacokinetics of imatinib
timeFrame: Each 28 day cycle
measure: Dose Expansion, Recommended Phase 2 Dose Determination, and Dose Expansion: Pharmacokinetics of imatinib
timeFrame: Each 28 day cycle
measure: Dose Expansion, Recommended Phase 2 Dose Determination, and Dose Expansion: Pharmacokinetics of imatinib
timeFrame: Each 28 day cycle
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
References: