Bezuclastinib in Systemic Mastocytosis
The Company is actively enrolling patients into APEX Part 2 which is anticipated to complete enrollment in Q1 2025 with top-line results expected in mid-2025.
Phase 2 SUMMIT Trial
Patient Demographics
SUMMIT is a registration-directed, randomized, double-blind, placebo-controlled, global, multicenter, clinical trial of bezuclastinib in patients with NonAdvSM. In SUMMIT Part 1, patients received bezuclastinib or placebo for a 12-week period to determine the recommended dose for use in the pivotal portion of the trial, SUMMIT Part 2. Earlier this year, the Company announced that the recommended go-forward dose was selected at once-daily 100 mg. After the initial 12-week period, all patients were given the opportunity to receive bezuclastinib in the SUMMIT Open Label Extension (“OLE”). The clinical results presented at ASH 2024 focus on 27 patients in the OLE who were treated with the once-daily 100 mg dose of bezuclastinib. The median age of patients at study entry was 52 years (ranging from 36-76 years). One patient had received prior avapritinib.
Patient Reported Outcomes (“PRO”) Data
SUMMIT patients were evaluated for signs of clinical activity over 24 weeks using multiple PRO measures, including the Mastocytosis Symptom Severity Daily Diary (“MS2D2”) and the Mastocytosis Quality-of-Life (“MC-QoL”) scale. Updated clinical data presented at ASH 2024 show:
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56% mean improvement in Total Symptom Score (“TSS”) at 24 weeks |
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76% of patients demonstrated >50% reduction from baseline in MS2D2 TSS with 88% of patients exceeding 30% reduction from baseline after 24 weeks |
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49% mean improvement in MC-QoL Total Score at 24 weeks |
At 24 weeks of treatment, 31% of patients have already reduced or discontinued best supportive care (“BSC”) medications.
Pharmacodynamic Data
Bezuclastinib showed rapid, deep, and sustained reductions in serum tryptase over the course of 24 weeks of treatment including:
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89% of patients had >50% decrease in serum tryptase levels by four weeks of treatment |
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95% of patients with baseline tryptase ≥20ng/mL achieved <20ng/mL by week 24 |
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84% of patients with baseline serum tryptase >11.4ng/ml achieved <11.4ng/mL by week 24 |
Safety Data
As of the data cutoff, August 29, 2024, the median duration of bezuclastinib treatment was 56 weeks for patients in the active arm and 40 weeks for placebo patients who crossed over to the OLE. The majority of treatment emergent adverse events were low grade and reversible with no treatment-related bleeding or cognitive impairment events reported. The most common treatment related adverse events were hair discoloration and transaminase elevations. All patients experiencing elevated transaminases were asymptomatic and reversible: five patients resolved without any dose modifications and remain on study; two patients resolved with dose reduction and remain on study, one of whom re-escalated to original dose; and two patients resolved following discontinuation, one of whom was presented previously at ASH 2023. There were no other discontinuations due to adverse events.
SUMMIT Enrollment Update
The Company also announced on December 9, 2024 that enrollment in the registration-directed SUMMIT Part 2 study is now complete. In the nine months between February and October 2024, 265 NonAdvSM patients were screened for SUMMIT Part 2 at 70 clinical sites, concentrated predominantly in the U.S. and Western Europe. More than 90% of these patients were naïve to KIT inhibitor therapy. A total of 179 patients were enrolled and top-line results from the trial are expected in July 2025.