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

Open to people ages 18 years and up

• Documented diagnosis of advanced/metastatic KIT-mutant GIST
• Documented disease progression on imatinib as current or prior therapy or is treatment naïve, as follows:
  • DES: Participant is progressing or progressed on imatinib in any prior line of therapy.
  • EXP Cohort A: Participant is progressing or progressed on imatinib and has not received additional intervening therapy before study participation.
  • EXP Cohort B: Participant has progressed on imatinib and sunitinib only and has not received additional intervening therapy before study participation.
  • EXP Cohort C: Participant has newly diagnosed advanced/metastatic GIST and is treatment naïve in the advanced/metastatic setting.
• 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.

• 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.