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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат ziftomenib
  menin inhibitor
• Препарат imatinib mesylate
  kinase inhibitor

Первичные конечные точки

• Dose Escalation: Dose Limiting Toxicity (DLT) [Срок оценки: Cycle 1 (first 28 day cycle)]
• Descriptive statistics of Adverse Events (AEs) [Срок оценки: 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) [Срок оценки: Up to 2 years following start of treatment with ziftomenib]

Вторичные конечные точки (12)

• Recommended Phase 2 Dose Determination and Dose Expansion: CBR [Срок оценки: Up to 2 years following start of treatment with ziftomenib]
• Overall Response Rate (ORR) [Срок оценки: Up to 2 years following start of treatment with ziftomenib]
• Progression Free Survival (PFS) [Срок оценки: Up to 2 years following start of treatment with ziftomenib]
• Duration of Response (DoR) [Срок оценки: Up to 2 years following start of treatment with ziftomenib]
• Overall Survival (OS) [Срок оценки: Up to 2 years following start of treatment with ziftomenib]
• Maximum plasma concentration (Cmax) [Срок оценки: Day 1 of each cycle; each cycle is 28 days]
• Time to maximum plasma concentration (Tmax) [Срок оценки: Day 1 of each cycle; each cycle is 28 days]
• Area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC 0-last) [Срок оценки: Day 1 of each cycle; each cycle is 28 days]
• Area under the concentration-time curve over a dosing interval (AUC tau) [Срок оценки: Day 1 of each cycle; each cycle is 28 days]
• Maximum plasma concentration (Cmax) [Срок оценки: Day 1 of each cycle; each cycle is 28 days]
• Time to maximum plasma concentration (Tmax) [Срок оценки: Day 1 of each cycle; each cycle is 28 days]
• Area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC 0-last) [Срок оценки: Day 1 of each cycle; each cycle is 28 days]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 32 центра

• University of Alabama at Birmingham — Birmingham
• Mayo Clinic Cancer Center — Phoenix
• University of California, San Diego — La Jolla
• University of Southern California — Los Angeles
• University Of California, Irvine — Orange
• Stanford Cancer Institute — Palo Alto
• UCLA Santa Monica Medical Center — Santa Monica
• University of Colorado Cancer Center — Aurora
• … и ещё 24 центра

Идентификаторы

NCT: NCT06655246 · KO-MEN-015

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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