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

NCT06208748 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: SARC044
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Gastrointestinal Stromal Tumors; GIST

Keywords

GIST; Gastrointestinal Stromal Tumors; Sarcoma; Sunitinib; Bezuclastinib; exon 11 or exon 9 primary KIT mutation

Outcome Measures

Primary Outcomes (1)

• To estimate the median progression free survival (mPFS)

  mPFS will be summarized with a Kaplan-Meier curve

  From the time of first dose to the occurrence of disease progression (as accessed by mRECIST v1.1) or death due to any cause prior to documented disease progression, up to 2 years..

Secondary Outcomes (6)

• To determine KIT mutations in tumor tissue and circulating tumor DNA (ctDNA) associated with primary and acquired resistance to combination bezuclastinib and sunitinib.

  1 year

• To determine the objective response rate (ORR; complete responses + partial responses) at 16 weeks and total ORR in patients treated with bezuclastinib in combination with sunitinib.

  16 weeks

• To determine the clinical benefit rate (complete responses + partial responses + stable disease) at 16 weeks in patients treated with bezuclastinib in combination with sunitinib.

  16 weeks

• To estimate the overall survival, including the overall survival rates at year one and year two.

  1 year, 2 year

• To describe the adverse event profile of bezuclastinib in combination with sunitinib.

  1 year

Study Arms (1)

bezuclastinib in combination with sunitinib

EXPERIMENTAL

Bezuclastinib 600 mg (tablet) administered orally daily Sunitinib 37.5 mg administered orally daily Patients will begin bezuclastinib and add sunitinib 2 weeks later. Each cycle is 28 days.

Drug: Bezuclastinib in combination with sunitinib

Interventions

Bezuclastinib in combination with sunitinib DRUG

Bezuclastinib in combination with sunitinib (sutent)

bezuclastinib in combination with sunitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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.

Sponsors & Collaborators

• Sarcoma Alliance for Research through Collaboration: lead
• Cogent Biosciences, Inc.: collaborator
• Dana-Farber Cancer Institute: collaborator
• The Life Raft Group: collaborator

Study Sites (4)

Sylvester Comprehensive Cancer Center, University of Miami

Miami, Florida, 33136, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors; Sarcoma

Interventions

Sunitinib

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Candace Haddox, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

• Andrew Wagner, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2023
• First Posted: January 17, 2024
• Study Start: August 1, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: October 31, 2025

Record last verified: 2025-10

Locations

US (4)