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

Phase 1RecruitingNCT06655246

Kura Oncology, Inc.157 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

157

Conditions

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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 Outcomes

Recommended Phase 2 Dose Determination and Dose Expansion: CBR

CBR is CR + PR + SD assessed per RECIST v1.1 modified for GIST

Time frame: Up to 2 years following start of treatment with ziftomenib

Overall Response Rate (ORR)

ORR is CR + PR assessed per RECIST v1.1 modified for GIST

Time frame: Up to 2 years following start of treatment with ziftomenib

Progression Free Survival (PFS)

Assessed per RECIST v1.1 modified for GIST

Time frame: Up to 2 years following start of treatment with ziftomenib

Duration of Response (DoR)

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

Time frame: Up to 2 years following start of treatment with ziftomenib

Overall Survival (OS)

Defined as the time from first dose of ziftomenib or imatinib (whichever is dosed first) until death from any cause

Time frame: Up to 2 years following start of treatment with ziftomenib

Maximum plasma concentration (Cmax)

Cmax of ziftomenib