Dr Rein on Symptom Burden Improvements With Bezuclastinib in Systemic Mastocytosis

“Patients who received bezuclastinib had a significant, rapid, durable…and clinically meaningful improvement in their TSS in comparison with patients who received placebo.”

Lindsay A.M. Rein, MD, an associate professor of medicine, hematologic malignancies and cellular therapy and a member of the Duke Cancer Institute, discussed key findings from the primary analysis of the phase 2 SUMMIT trial (NCT05186753) investigating bezuclastinib (CGT-9486) in adult patients with non-advanced systemic mastocytosis (SM).

The primary end point of SUMMIT was defined as the mean change in total symptom score (TSS) from baseline to week 24. To accurately capture these changes, the study used the Mastocytosis Symptom Severity Daily Diary (MS2D2) TSS, which Rein described as a fit-for-purpose patient-reported outcome tool designed specifically for the needs of this patient population.

The MS2D2 tool is comprehensive, addressing 17 different signs and symptoms characteristically found in patients living with SM, Rein said. Within this scoring system, patients are required to rate the severity of their symptoms on a scale from 0 to 10, where 0 indicates the absence of symptoms, and 10 represents the most severe manifestation. Whereas 17 symptoms were tracked, the study’s total score was derived from 11 specific symptoms categorized into 4 symptom domains, resulting in a maximum potential score of 110 points.

The trial successfully met its primary end point, demonstrating that bezuclastinib provided a statistically and clinically meaningful improvement in TSS vs placebo. The data revealed that this improvement was significant, rapid, and durable over the course of the study compared with placebo. Notably, the placebo-controlled effect size showed a difference of –8.91 points (95% CI, –13.56 to –4.26; P < .001) in favor of the patients receiving bezuclastinib.

Disclosures: Rein reported performing consultancy roles (including expert commentary) with Sobi, Novartis, Cogent Biosciences, Blueprint Medicines, and Incyte; receiving honoraria from Merck, Cogent Biosciences, and Blueprint Medicines; and receiving research funding from Cogent Biosciences, Merck, Incyte, Blueprint Medicines, and Novartis.