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

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

Gastrointestinal Stromal Tumor

Recruiting

2

Start Date 06/01/2024

Age of Trial (yrs) .5

Gleevec-resistant

KIT inhibitor

Inhibit all resistant KIT/PDGFRa mutations

Specifically GIST and only GIST

SARC044

Sarcoma Alliance for Research through Collaboration

SARC Office: (734) 930-7600 SARC044@sarctrials.org

Oral

Sponsors and Collaborators
Sarcoma Alliance for Research through Collaboration
Cogent Biosciences, Inc.
Dana-Farber Cancer Institute
The Life Raft Group

Investigators
Principal Investigator: Candace Haddox, MD Dana-Farber Cancer Institute
Principal Investigator: Andrew Wagner, MD, PhD Dana-Farber Cancer Institute


Detailed Description:

This is an open label, single arm, phase 2 trial investigating bezuclastinib plus sunitinib in patients with GIST who have previously progressed on sunitinib. After washout, patients will begin bezuclastinib and add sunitinib 2 weeks later. Patients will continue on treatment until progression, unacceptable toxicity, or withdrawal of consent. Patients may stay on treatment beyond progression if there is clinical benefit in the opinion of the investigator. Imaging response assessments will be performed every 8 weeks until the participant reaches 15 months on study. After 15 months, response assessments may be performed every 3 months. Circulating tumor DNA (ctDNA) will be collected at baseline, with sequential initiation of bezuclastinib and sunitinib, at the first response assessment, and at the time of progression. In a subset of 20 patients, PET/CT will be performed at baseline and with sequential initiation of bezuclastinib and sunitinib, and tumor biopsies will be performed on cycle 2 day 1 for correlative studies. EORTC QLQ-C30 will be administered during the study to assess patient-reported quality of life.

Partial Criteria:

Criteria

Partial Inclusion Criteria:

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.

Partial Exclusion Criteria:

Prior exposure to bezuclastinib.

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.