A Study of Ziftomenib in Combination With Imatinib in Patients With Advanced Gastrointestinal Stromal Tumors (GIST)
A Study of Ziftomenib in Combination With Imatinib in Patients With Advanced Gastrointestinal Stromal Tumors (GIST)
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 as current or prior therapy, or are treatment naive.
Phase I,
Sarcoma
Phase I
Adults
Mol. targeted/Immunotherapy/Biologics
Imatinib,
Ziftomenib
Keedy, Vicki
National
Vanderbilt University
12-01-2025
Eligibility
18 Years and older
ALL
false
Inclusion Criteria:
Documented diagnosis of advanced/metastatic KIT-mutant GIST
Documented disease progression on imatinib as current or prior therapy or is treatment nave, 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 nave 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
Participant, or legally authorized representative, must be able to understand and provide written informed consent before the first screening procedure.
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.
Documented diagnosis of advanced/metastatic KIT-mutant GIST
Documented disease progression on imatinib as current or prior therapy or is treatment nave, 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 nave 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
Participant, or legally authorized representative, must be able to understand and provide written informed consent before the first screening procedure.
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.
