Bezuclastinib

The cited U.S. epidemiology study reported an increase in annual age-adjusted incidence from 0.55 per 100,000 in 2001 to 0.78 per 100,000 in 2011. Severe fatigue occurred in 30% of participants with GIST and 33% of those receiving a TKI in the cited fatigue study. A recurrence-cost study reported an additional $4464 per patient per month in total healthcare costs for patients with recurrence.

PEAK randomized 413 participants: 204 to bezuclastinib plus sunitinib and 209 to sunitinib. Median progression-free survival by blinded independent central review was 16.5 versus 9.2 months. Objective response rates were 45.6% versus 25.8%. Grade 3 or higher ALT/AST increases were reported in 10.8% versus 1.4%. Treatment-related adverse events led to study-treatment discontinuation in 7.4% versus 3.8%. Overall-survival data remained immature in the subsequent company update.

The reported PEAK results support a progression-free-survival and response-rate benefit for bezuclastinib plus sunitinib compared with sunitinib alone after prior imatinib. Overall-survival data remained immature. The application received Priority Review, and the reported target action date was November 30, 2026. The company continued to describe GIST approval as potential rather than completed.