(P 425) BEZUCLASTINIB EXPANDED ACCESS PROGRAM (EAP) FOR PATIENTS WITH GASTROINTESTINAL STROMAL TUMORS (GIST)

Objective: Imatinib is the worldwide standard for first-line therapy of advanced KIT-mutant GIST. However, secondary resistance mutations in the KIT ATP-binding domain (exon 13/14), activation loop (exon 17/18), or both develop and result in loss of imatinib-sensitivity.
Bezuclastinib is an oral, potent, selective type 1 tyrosine kinase inhibitor (TKI) targeting KIT mutations in exons 9, 11, 17, and 18. High selectivity of bezuclastinib allows it to be combined with sunitinib, which targets mutations in exons 9, 11, 13, and 14. Whereas no single TKI inhibits all KIT mutations, the combination of bezuclastinib + sunitinib provides activity against all primary and secondary KIT mutations relevant in GIST. In a Phase 1/2 study, patients with relapsed and/or refractory GIST treated with bezuclastinib + sunitinib (n=15) experienced clinical benefit and an acceptable safety profile.
Bezuclastinib + sunitinib is being evaluated in a registrational Phase 3 study in patients with GIST (Peak, NCT05208047). Given that the clinical trial is fully enrolled, the GIST EAP (NCT06948955) is designed to provide access to investigational bezuclastinib outside of a clinical trial to patients with GIST who meet specific criteria and have no comparable or satisfactory alternative therapy to treat the disease.

Methods: Key eligibility criteria for the EAP include diagnosis of 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; and acceptable laboratory parameters. Key exclusion criteria include prior or known intolerance to sunitinib; eligibility for and/or enrolled in an ongoing bezuclastinib clinical trial; or discontinuation of investigational bezuclastinib due to toxicity or withdrawal of consent. Patients will receive oral bezuclastinib 600 mg + sunitinib 37.5 mg (locally sourced). The treating physician will be responsible for standard of care patient assessments and reporting of any serious adverse events. In collaboration with interested sites, real-world data may be collected in the future. The duration of bezuclastinib treatment through the EAP will be determined by the treating physician but may continue until regulatory approval and commercial availability. The EAP is currently open to receive EAP requests from treating physicians for patients residing in the United States.

Results: N/A

Conclusion: N/A