Next-Generation KIT Inhibitor Shows Promise in Systemic Mastocytosis

Emerging data presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting highlighted the continued progress in targeted therapies for systemic mastocytosis, including next-generation approaches designed to improve safety and tolerability.

In this exclusive MedPage Today video, Cem Akin, MD, PhD, of the University of Michigan in Ann Arbor, discusses findings from the SUMMIT trial evaluating bezuclastinib and how it compares with existing therapies.

Following is a transcript of his remarks:

In the SUMMIT trial, results were similar to the PIONEER trial in terms of placebo versus active drug, which was used at the dose of 100 mg. And there were very deep reductions in disease biomarkers like tryptase levels, and almost all patients hit 50% or more improvement of the tryptase level, a substantial number, and very impressive improvements in allele burden.

So the safety profile was a little different. And, of course, bezuclastinib was designed not to cross the blood-brain barrier to minimize the risk of cognitive side effects that were seen in the high-dose avapritinib trial. And those side effects were not encountered with bezuclastinib. But the patient enrollment obviously also was limited to patients with normal platelet counts, and those were the patients who experienced intracranial bleeds in the PIONEER trial. In the bezuclastinib SUMMIT trial, again, there were no intracranial bleeds or cognitive dysfunction.

Now, the side effects were mainly hair whitening that were encountered in a substantial number of patients and also taste changes, dysgeusia, and in some patients liver function abnormalities, the increased LFT [liver function tests] and ALT [alanine aminotransferase] levels. And so those were generally grade 1 and 2 events, but moderate to severe elevations were encountered in some patients. And I think it required discontinuation of the drug in about 5% to 6% of the patients due to the liver functional elevation.