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

Kura Oncology

Status and phase: Enrolling; Phase 1

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

Treatments: Drug: ziftomenib; Drug: imatinib mesylate

Study type: Interventional

Funder types: Industry

Identifiers

NCT06655246

KO-MEN-015

Details and patient eligibility

About

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.

Enrollment: 157 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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157 participants in 3 patient groups

Dose Escalation

Experimental group

Description:

Ziftomenib plus imatinib

Treatment:

Drug: imatinib mesylate

Drug: ziftomenib

Recommended Phase 2 Dose Determination

Experimental group

Description:

Ziftomenib plus imatinib

Treatment:

Drug: imatinib mesylate

Drug: ziftomenib

Dose Expansion

Experimental group

Description:

Ziftomenib plus imatinib

Treatment:

Drug: imatinib mesylate

Drug: ziftomenib