SARC044: A Phase II Trial of Bezuclastinib in Combination With Sunitinib in Patients With GIST

Running, not enrolling · Phase 2

Conditions studied: Gastrointestinal Stromal Tumors, GIST

In brief

This is an open label, single arm, phase 2 trial investigating bezuclastinib plus sunitinib in patients with GIST who have previously progressed on sunitinib.

Key facts

Study ID

NCT06208748

Run by

Sarcoma Alliance for Research through Collaboration

People needed

40

Starts

2024-08-01

Expected to finish

2027-06-01

Last updated by the study team

2025-10-31

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age minimum of 18 years
• Histologically confirmed, inoperable or metastatic GIST with an exon 11 or exon 9 primary KIT mutation. Other primary KIT mutations (e.g., exon 13, exon 17) will be considered on a case-by-case basis after discussion with the Principal Investigator. Pathology reports including mutational analysis should be available for review by the Sponsor.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 (See Appendix A).
• Prior progression on or intolerance to imatinib. Imatinib intolerance is defined as discontinuation of imatinib due to an adverse event(s) related to treatment with imatinib that was not manageable with dose modifications.
• Documented disease progression on sunitinib of at least 25 mg daily as continuous treatment, or 37.5 mg daily with the 4 weeks on/2 weeks of schedule.
• At least one site of measurable disease on CT/MRI scan as defined by modified RECIST version 1.1 (mRECIST v1.1) criteria.
• Resolution of toxicities from prior therapy to ≤Grade 1 (or baseline), including clinically significant laboratory abnormalities, prior to the first dose of the study drug.
• Adequate organ function:
• Absolute Neutrophil Count (ANC) ≥ 1 x 109/L (unsupported for 7 days, or 14 days if pegfilgrastim was administered)
• Platelets ≥ 100 x 109/L (unsupported for 14 days)
• Hemoglobin ≥8 g/dL (unsupported for 14 days)
• ALT and AST ≤ 2.5 x institutional upper limit of normal (ULN) or ≤ 5.0 x institutional ULN in the presence of hepatic metastases.
• Serum bilirubin ≤ 1.5 x institutional ULN. NOTE: Patients with elevated bilirubin secondary to Gilbert's disease are eligible to participate in the study provided that direct bilirubin ≤1.5 x institutional ULN and indirect bilirubin ≤3 x institutional ULN
• Estimated glomerular filtration rate ≥45 mL/min/1.73 m2
• Ability and willingness to provide written, voluntary informed consent
• Ability to swallow pills
• For male subjects, unless having undergone permanent sterilization (includes bilateral orchidectomy), agreement to use effective barrier contraception (i.e., condoms) during the study treatment period and for 6 weeks after the last dose of study drug.
• For women of childbearing potential (WOCBP), confirmation of negative serum or urine pregnancy test prior to dosing with the study drug and agreement to the use of highly effective method of contraception with or without a barrier contraception method during the study treatment period and for 6 weeks after the last dose of the study drug. Female subjects who are using hormonal contraception must agree to remain on a stable regimen throughout the study unless a change is deemed medically necessary by the Investigator.
• WOCBP are defined as defined as physiologically and anatomically capable of becoming pregnant, unless they meet one of the following conditions:
• Postmenopausal: 12 months of natural (spontaneous) amenorrhea without an alternative medical cause
• Prior hysterectomy
• Prior bilateral oophorectomy
• Prior bilateral salpingectomy
• Highly effective methods of birth control includes:
• Combined (estrogen- and progesterone-containing) hormonal contraception associated with inhibition of ovulation, delivered orally, intravaginally, or transdermally

You may not qualify if…

• Prior exposure to bezuclastinib.
• 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 the study drug.
• Received strong CYP3A4 inhibitor(s) or inducer(s) within 14 days or 5 drug half-lives before the first dose of the study drug, whichever is longer, or the need to continue treatment with strong CYP3A4 inhibitor(s) or inducer(s) during the study.
• GIST without primary activating mutations in KIT exons 11 or 9. Other primary KIT activating mutations will be considered on a case-by-case basis. Patients with GIST with other mutations (e.g., PDGFRA, SDHx, BRAF, or NF1) or unknown genotype are excluded.
• Known or suspected hypersensitivity to bezuclastinib or sunitinib and their components.
• Unacceptable toxicity with prior sunitinib at 25 mg daily.
• Clinically significant cardiac disease, defined by any of the following:
• Clinically significant cardiac arrhythmias and/or the need for antiarrhythmic therapy (excluding beta blockers or digoxin). Subjects with controlled atrial fibrillation are not excluded.
• Congenital long QT syndrome or use of concomitant medications known to prolong the QT interval as defined in Appendix D.
• A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >470 milliseconds [ms] using Fridericia's QT correction formula).
• Clinically significant history of cardiac disease or congestive heart failure >New York Heart Association Class II. Subjects must not have unstable angina (anginal symptoms at rest) or new-onset angina within 3 months or myocardial infarction within 6 months prior to enrollment.
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within the 6 months before study drug initiation (except for adequately treated catheter-related venous thrombosis occurring more than 1 month before the first dose of study drug).
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen may be included after discussion with the Principal Investigator.
• Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol.
• Patients known to be seropositive for human immunodeficiency virus (HIV) 1 or 2. HIV testing is not required as part of screening.
• Major surgery (including abdominal laparotomy) within 4 weeks prior to the first dose of study drug, or subjects who have not recovered adequately from prior surgery.
• Gastrointestinal abnormalities including, but not limited to, significant nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption
• Any active bleeding, excluding hemorrhoidal or gum bleeding
• Women who are pregnant or nursing/breastfeeding.
• Patients with untreated central nervous system metastatic disease.
• Inability to comply with protocol required procedures
• Active, uncontrolled, systemic bacterial, fungal, or viral infections at Screening. NOTE: Oral antibiotics for a controlled infection (e.g., urinary tract infection) are permitted provided that the symptoms are mild and expected to resolve with appropriate treatment at the discretion of the investigator. Subjects on antimicrobial, antifungal, or antiviral prophylaxis are not specifically excluded if all other inclusion/exclusion criteria are met.

Where it is running

• Sylvester Comprehensive Cancer Center, University of Miami — Miami, Florida, United States
• Dana Farber Cancer Institute — Boston, Massachusetts, United States
• Oregon Health & Science University — Portland, Oregon, United States
• Fox Chase Cancer Center — Philadelphia, Pennsylvania, United States

Full record on ClinicalTrials.gov

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