The phase 3 PEAK trial showed that combining bezuclastinib, a selective oral KIT inhibitor, with sunitinib significantly improves outcomes in patients with advanced gastrointestinal stromal tumors (GIST) who have progressed after first-line therapy.
The combination reduced the risk of disease progression or death by 50%, with median progression-free survival of 16.5 months versus 9.2 months for sunitinib alone. Objective response rates nearly doubled (45.6% vs 25.8%), and complete responses increased (6.4% vs 1.9%). Disease control and duration of response were also improved.
The study included 413 patients, most with KIT exon 11 mutations, treated in a randomized phase 3 design with crossover allowed. While grade ≥3 adverse events were more frequent in the combination arm, including reversible liver enzyme elevations, no new safety signals or treatment-related deaths were observed. Other toxicities were similar between groups.