IRB Study Number 25-892
Status Recruiting
Institute Taussig Cancer Institute
Description
The purpose of this EAP is to provide investigational bezuclastinib to patients with a diagnosis of GIST with no comparable or satisfactory alternative therapy options. Bezuclastinib will be coadministered with sunitinib.
Inclusion Criteria
Individuals must meet all of the following inclusion criteria:
- Able to provide written informed consent.
- Able and willing to commit to recommended EAP assessments.
- ≥18 years of age.
- Able to swallow tablets.
- For women of childbearing potential, confirmation of a negative serum pregnancy test prior to dosing and agreement to the use of a highly effective method of contraception during the EAP and for 6 weeks after the last dose of bezuclastinib. A barrier contraception method is also required for women using hormonal contraceptives that are CYP3A4 substrates (see Section 4.6.3);
For male patients able to father a child, agreement to use effective barrier contraception (ie, condoms) during the treatment period and for 6 weeks after the last dose of bezuclastinib. - Histologically confirmed locally advanced, metastatic, and/or unresectable GIST.
- Intolerant to imatinib or received prior imatinib therapy for treatment of advanced, metastatic, and/or unresectable GIST that resulted in disease progression.
- Meet clinically acceptable local laboratory results:
a. Absolute neutrophil count ≥ 1 × 109/L (unsupported for 7 days, or 14 days if pegfilgrastim was administered);
b. Hgb ≥ 8 g/dL (unsupported for 14 days);
c. Platelet count ≥ 100×109/L (unsupported for 14 days);
d. AST and ALT ≤ 2.5 × ULN or ≤ 5 × ULN in the presence of hepatic metastases;
e. Total bilirubin ≤ 1.5 × ULN; for patients with confirmed Gilbert’s syndrome, direct bilirubin ≤ 1.5 × ULN and indirect bilirubin ≤ 3 × ULN;
f. eGFR ≥ 45 mL/min/1.73 m2.
Exclusion Criteria
Individuals will be excluded from EAP participation if any of the following criteria apply:
- Patients who are eligible for and capable of participating in and/or enrolled in an on-going bezuclastinib clinical trial.
- Prior or known intolerance to sunitinib.
- Patients who have previously participated in a bezuclastinib clinical trial.
- Received strong CYP3A4 inhibitors/inducers within 14 days or 5 drug half-lives before the first dose, whichever is longer, or the need to continue treatment with strong CYP3A4 inhibitors or inducers during treatment with investigational bezuclastinib.
- Patients with persistent > Grade 2 toxicities from prior therapy.
- Known PDGFR driving mutations or known SDH deficiency.
- Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of EAP treatment.
- Gastrointestinal abnormalities including, but not limited to, significant nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption.
- History of clinically significant bleeding event within 30 days before the first dose or receiving anticoagulation for treatment of DVT or pulmonary embolism (patients receiving prophylactic anticoagulation for nonvalvular atrial fibrillation or prevention of DVT are allowed).
- Known hypersensitivity to bezuclastinib or sunitinib.
- Pregnant or currently breastfeeding.
- Prior anticancer drug less than 5 half-lives of the parent drug and/or its active metabolite(s) or 14 days (whichever is shorter) prior to the first dose of bezuclastinib. Note this does not apply to sunitinib.
- Prior or ongoing clinically significant illness, malignancy, medical or physical condition (eg, cardiac disease) that, in the opinion of the treating physicians or the Sponsor, could affect the safety of the patient or compromise participation in expanded access.
