Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.
Key Inclusion Criteria:
- Male or female patient ≥ 18 years of age.
- For Dose Escalation Phase Cohorts (Phase 1):
- Have histologically- or cytologically-confirmed unresectable or metastatic GIST.
- Have progressed on or are intolerant to imatinib therapy and have also received
at least 1 of the following: sunitinib, regorafenib, ripretinib, or avapritinib.
- For Expansion Phase Cohorts (Phase 2):
- Cohort 1:
- Have histologically- or cytologically confirmed unresectable or metastatic
GIST.
- Have progressed on or are intolerant to imatinib, sunitinib, regorafenib and
ripretinib.
- Cohort 2:
- Have histologically- or cytologically confirmed unresectable or metastatic
GIST.
- Have progressed on or are intolerant to imatinib and sunitinib. Patients in
this cohort are allowed to have received up to 1 additional line of therapy
in the advanced/metastatic setting.
- Cohort 3:
- Have histologically- or cytologically confirmed unresectable or metastatic
GIST.
- Have progressed on or are intolerant to imatinib (including in the adjuvant
setting).
- Have not received additional systemic therapy for advanced GIST.
- Have at least 1 measurable lesion as defined by modified RECIST 1.1
- Have archival or new tumor biopsy tissue available to submit for mutational testing.
Patients without appropriate archival tissue available may be discussed with the study
medical monitor and approved for enrollment on a case-by-case basis.
- Have Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2.
- Adequate renal, hepatic and bone marrow function as defined by the protocol.
- For female patients of childbearing potential, have a negative serum or urine beta
human chorionic gonadotropin (?-hCG) pregnancy test within 7 days prior to the first
dose of study drug.
o Note: female patients of nonchildbearing potential (postmenopausal; hysterectomy;
bilateral salpingectomy; or bilateral oophorectomy) do not require a pregnancy test.
- Female patients of childbearing potential must agree to abstain from heterosexual
intercourse or use a highly effective form of contraception with their sexual partners
during the dosing period and for a period of at least 30 days after the end of
treatment. Male patients with partners of childbearing potential must agree that they
will abstain from heterosexual intercourse or use condoms and their partners will use
highly effective contraceptive methods during the dosing period until at least 90 days
after the last dose of study drug.
- All toxicities from prior therapy have resolved to ≤ grade 1 according to the National
Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0), or
have resolved to baseline, at the time of first dose of study drug. Note:
treatment-related grade >1 alopecia, treatment related grade 2 peripheral neuropathy,
and treatment-related grade 2 hypothyroidism on a stable dose of thyroid hormone
replacement therapy are allowed if deemed irreversible.
Key Exclusion Criteria:
- Received systemic anticancer therapy (including cytotoxic chemotherapy,
investigational agent, antineoplastic monoclonal antibodies, or immunotherapy) less
than 5 half-lives or 14 days (whichever is shorter) prior to the first dose of study
drug.
- Patients known to be both KIT and PDGFRA wild-type.
- Received radiotherapy within 14 days prior to the first dose of study drug.
- Major surgical procedure within 28 days of the first dose of study drug. Minor
surgical procedures such as central venous catheter placement or minimally invasive
biopsy are allowed.
- Have known untreated or active central nervous system metastases.
- 12-lead electrocardiogram (ECG) demonstrating QT interval corrected by Fridericia's
formula (QTcF) >470 msec at screening, or history of long QTc syndrome.
- Have significant, uncontrolled, or active cardiovascular disease, including, but not
restricted to:
- Myocardial infarction (MI) within 6 months prior to the first dose of study drug
- Unstable angina within 6 months prior to first dose of study drug
- Symptomatic congestive heart failure (New York Heart Association classes II-IV)
within 6 months prior to first dose of study drug
- Clinically significant, uncontrolled atrial arrhythmia (as determined by the
Investigator)
- Any history of ventricular arrhythmia
- Cerebrovascular accident or transient ischemic attack within 6 months prior to
first dose of study drug
- Uncontrolled hypertension at study entry. Patients with hypertension should be
under treatment on study entry to control blood pressure.
- Have an active uncontrolled infection, including, but not limited to, the requirement
for intravenous antibiotics.
- Any active bleeding excluding hemorrhoidal or gum bleeding.
- For patients with a known human immunodeficiency virus (HIV) infection, have CD4+
T-cell counts <350 cells/uL or history of acquired immunodeficiency syndrome
(AIDS)-defining opportunistic infection within the past 12 months. Patients with HIV
infection should be on established antiretroviral therapy (ART) for at least 4 weeks
and have an HIV viral load less than 400 copies/mL prior to enrollment.
- Has known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, as
evidenced by detectable viral load (HBV-DNA or HCV-RNA, respectively). Risk of HBV
reactivation should be considered in all patients and the need for anti-HBV
prophylaxis should be carefully assessed. Patients with chronic HBV infection with
history of active disease who meet the criteria for anti HBV therapy should be on a
suppressive antiviral therapy to be eligible for enrollment. Patients who are HCV Ab
positive but HCV RNA negative due to prior treatment or natural resolution are
eligible. Patients on concurrent HCV treatment at the time of enrollment are allowed
if HCV RNA negative.
- Pregnant or breastfeeding.
- Patients with prior or concurrent malignancies other than GIST are allowed, except in
the case where, in the opinion of the Investigator, the natural history or treatment
of the other malignancy has the potential to interfere with the safety or efficacy
assessment of the study drug.
- Have any condition or illness that, in the opinion of the Investigator, might
compromise patient safety or interfere with the evaluation of the safety of the drug.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 2/9/23. Questions regarding updates should be directed to the study team contact.