Gastrointestinal Stromal Tumor (GIST), Gastrointestinal Stromal Cancer, Gastrointestinal Stromal Neoplasm, Gastrointestinal Stromal Tumor, Malignant, Gastrointestinal Stromal Cell Tumors
Conditions
Keywords
Gastrointestinal Stromal Tumor, Gastrointestinal Stromal Cancer, Gastrointestinal Stromal Neoplasm
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.
Interventions
DRUGziftomenib
menin inhibitor
DRUGimatinib mesylate
kinase inhibitor
Sponsors
Kura Oncology, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation: Dose Limiting Toxicity (DLT) | Cycle 1 (first 28 day cycle) | Rate of DLTs per dose level |
| Descriptive statistics of Adverse Events (AEs) | 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 | Per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 |
| Dose Expansion: Clinical benefit rate (CBR) | Up to 2 years following start of treatment with ziftomenib | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Recommended Phase 2 Dose Determination and Dose Expansion: CBR | Up to 2 years following start of treatment with ziftomenib | CBR is CR + PR + SD assessed per RECIST v1.1 modified for GIST |
| Overall Response Rate (ORR) | Up to 2 years following start of treatment with ziftomenib | ORR is CR + PR assessed per RECIST v1.1 modified for GIST |
| Progression Free Survival (PFS) | Up to 2 years following start of treatment with ziftomenib | Assessed per RECIST v1.1 modified for GIST |
| Duration of Response (DoR) | Up to 2 years following start of treatment with ziftomenib | 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 |
| Overall Survival (OS) | Up to 2 years following start of treatment with ziftomenib | Defined as the time from first dose of ziftomenib or imatinib (whichever is dosed first) until death from any cause |
| Maximum plasma concentration (Cmax) | Day 1 of each cycle; each cycle is 28 days | Cmax of ziftomenib |
| Time to maximum plasma concentration (Tmax) | Day 1 of each cycle; each cycle is 28 days | Tmax of ziftomenib |
| Area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC 0-last) | Day 1 of each cycle; each cycle is 28 days | AUC 0-last of ziftomenib |
| Area under the concentration-time curve over a dosing interval (AUC tau) | Day 1 of each cycle; each cycle is 28 days | AUC tau of ziftomenib |
Countries
United States
Contacts
CONTACTKura Medical Information 844-KURAONC
Outcome results
None listed