Bezuclastinib treatment leads to reductions in serum tryptase levels and bone marrow mast cells in patients with advanced systemic mastocytosis, according to results from a phase 2 clinical trial named APEX.

Moreover, it leads to a decrease in blood KIT D816V variant allele fraction. The treatment’s initial safety and tolerability profiles are favorable with no edema, cognitive effects, or intracranial bleeding events.

These results were presented at the European Hematology Association (EHA) 2022 Congress.

“I am very impressed with the early, encouraging results presented today from the APEX study,” Daniel DeAngelo, MD, PhD, chief of the Division of Leukemia at the Dana-Farber Cancer Institute, Boston, Massachusetts, and investigator in the APEX trial, said in a press release

“If results like these can be shown in a larger set of patients with [advanced systemic mastocytosis], I believe bezuclastinib has the potential to help us take a big step forward in treating systemic mastocytosis patients.” 

Read more about the types of systemic mastocytosis

APEX is a global, open-label, multicenter, 2-part trial that aims to evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of bezuclastinib in patients with advanced systemic mastocytosis.

By the data cutoff date of May 24, 2022, 11 patients had been treated with 50, 100, or 200 mg of bezuclastinib twice a day or 400 mg of bezuclastinib once a day. Of these, 2 had aggressive systemic mastocytosis, 8 had systemic mastocytosis with an associated hematologic neoplasm, and 1 had mast cell leukemia. Two patients had received avapritinib and midostaurin treatment in the past.

All 11 patients had at least a 50% reduction in serum tryptase levels with a median reduction of 89%. The bone marrow of 8 patients was evaluated and showed a reduction in mast cells of 50% or more. The bone marrow mast cell aggregates were completely cleared in 6 patients.

Most adverse events were grade 1/2. Three patients had grade 3 events, which included anemia, neutropenia, and hypersensitivity/mediator flare.

Bezuclastinib is a selective KIT D816V inhibitor being developed by Cogent Biosciences. APEX is still recruiting participants.


Cogent Biosciences announces positive initial clinical data from ongoing phase 2 APEX trial evaluating bezuclastinib in patients with advanced systemic mastocytosis (AdvSM). News release. Cogent Biosciences, Inc; June 10, 2022. 

(Apex) CGT9486 in patients with advanced systemic mastocytosis. August 9, 2021. Updated February 2, 2022. Accessed June 16, 2022.