Dr George on the Data for Bezuclastinib in Non-Advanced Systemic Mastocytosis from the SUMMIT Trial

“Overall, data [from the SUMMIT trial were] very exciting because they show a normalization of the bone marrows in patients.”

Tracy George, MD, president of the Innovation Business Unit and chief scientific officer at ARUP Laboratories, as well as a professor of pathology at the Spencer Fox Eccles School of Medicine at the University of Utah, discussed data from the phase 2 SUMMIT trial (NCT05186753) on bezuclastinib (CGT9486) in patients with non-advanced systemic mastocytosis.

At the 2025 ASH Annual Meeting and Exposition, George presented data on key findings for bezuclastinib on the pathobiology of mastocytosis, including changes in bone marrow mast cells, tryptase levels, and KIT D816V variant allele frequency (VAF). She said these findings from SUMMIT showcase the potency of bezuclastinib, specifically its ability to normalize bone marrow in patients. George noted that normalization data for patients in the bezuclastinib arm vs the placebo arm were plentiful, as 74% patients in the bezuclastinib arm had mast cell aggregates at baseline (n = 119) compared with 13% at 24 weeks (n = 101); 78% of patients in the placebo arm had mast cell aggregates at baseline (n = 60) compared with 60% at 24 weeks (n = 51).

Moreover, mast cell percentages in bone marrow for the bezuclastinib arm were 18% (n = 119) and 5% (n = 102) at screening and week 24, respectively, vs 16% (n = 60) and 14% (n = 50), respectively, for the placebo arm. George mentioned that spindle-shaped mast cells are a characteristic of non-advanced systemic mastocytosis, and that patients’ mean percentage of spindle-shaped mast cells to total mast cells was respectively 76% and 50% (n = 119; n = 95) for the bezuclastinib arm vs 75% and 70% (n = 60; n = 50) for the placebo arm. Additionally, George added that both CD25 and CD30, which are commonly expressed by non-advanced systemic mastocytosis mast cells, were significantly reduced by week 24 in the bezuclastinib arm compared with increased expressions for each in the placebo arm.

George continued by noting how the mean percentage of bone marrow cellularity in the smoldering non-advanced systemic mastocytosis subgroup decreased from 73% at baseline (n = 8) to 40% at week 24 (n = 6).

Notably, George explained 97% of patients in the bezuclastinib arm achieved at least a 50% reduction in KIT D8167V VAF in both blood and bone marrow at 24 weeks compared with 3% in the placebo arm. Serum tryptase levels were also reduced to normal levels by bezuclastinib after 24 weeks in patients with elevated serum tryptases levels of at least 20 ng/mL (83%; n = 89) and 11.4 ng/mL (78%; n = 104). Finally, at 24 weeks, 55% of patients in the bezuclastinib arm no longer met World Health Organization diagnostic criteria for non-advanced systemic mastocytosis.