Evaluating bezuclastinib for the treatment of advanced gastrointestinal stromal tumours

Advanced gastrointestinal stromal tumors (GISTs) are usually driven by KIT or PDGFRA and treated with sequential tyrosine kinase inhibitors. After imatinib, several distinct secondary KIT-resistant clones may coexist within and between lesions, limiting the coverage of any single later-line inhibitor.

This Drug Evaluation reviews the chemistry, active-state pharmacology, preclinical activity, pharmacokinetics, clinical efficacy, safety and regulatory status of bezuclastinib, with emphasis on its combination with sunitinib. PubMed, ClinicalTrials.gov, regulatory sources and major congress proceedings were searched through 13 August 2026.

Bezuclastinib is best viewed as a combination-enabling type I KIT inhibitor that complements the type II inhibitor sunitinib. In PEAK, the combination improved median progression-free survival from 9.2 to 16.5 months and objective response rate from 25.8% to 45.6%, at the cost of more grade 3 or higher toxicity and treatment modification. Pending approval, it is likely to become a preferred second-line option for suitable patients with KIT-driven GIST. Mature survival, post-combination sequencing, resistance mechanisms, long-term patient-reported outcomes and real-world tolerability remain important evidence gaps.