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

Eligibility: Inclusion Criteria
  •   Key
  •   * 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.