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Apex part I: Bezuclastinib for AdvSM
By Ella Dixon
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AdvSM is an aggressive, life-threatening subtype of SM that leads to the accumulation of neoplastic mast cells.1 Therapies providing durable responses and acceptable toxicity profiles are currently lacking.1 Bezuclastinib, an oral, selective type I TKI, acts against the KIT D816V mutation; the driver mutation in 95% of patients with SM.1 Results from part 1 of the 2-part phase II, multicenter Apex trial (NCT04996875) investigating the efficacy and safety of bezuclastinib in patients with AdvSM were presented by DeAngelo at the 66th ASH Annual Meeting and Exposition.1 In part 1 of the study, 32 patients were randomized to receive 50 mg BID, 100 mg BID, 200 mg BID, or 400 mg QD to identify the optimal dose for part 2 of the trial.1 |
| Key learnings |
| Among 27 response-evaluable patients across all doses, the ORR per mIWG-MRT-ECN was 52%, with a 26% CR rate. The ORR was 61% in TKI-naive patients (n = 18), with no CRs in patients with prior TKI exposure (n = 9). |
| Median PFS and DOR were not reached in part 1 of the trial, with a PFS rate of 82% at 24 months. No patients had progression of SM; however, 7 patients experienced associated hematologic neoplasm progression. |
| The median treatment duration was 16.2 months. The majority of hematologic AEs were low grade, reversible, and did not require dose reductions. Of 12 patients who required a dose reduction due to AEs, 8 were originally randomized to 200 mg BID or 400 mg QD. |
| Optimal outcomes were observed with 100 mg BID. An ORR of 83% was seen in this group, with no discontinuations due to AEs. Part 2 of the study is ongoing. |
Abbreviations: AdvSM, advanced systemic mastocytosis; AE, adverse event; ASH, American Society of Hematology; BID, twice daily; CR, complete response; DOR, duration of response; mIWG-MRT-ECN; International Working Group-Myeloproliferative Neoplasms Research and Treatment and European Competence Network on Mastocytosis; ORR, overall response rate; PFS, progression-free survival; SAE, severe adverse event; SM, systemic mastocytosis; TKI, tyrosine kinase inhibitor; QD, once daily.
- DeAngelo D. Apex part 1: Updated assessment of bezuclastinib (CGT9486), a selective KIT D816V tyrosine kinase inhibitor, in patients with advanced systemic mastocytosis (AdvSM). Oral abstract #659. 66th American Society of Hematology (ASH) Annual Meeting and Exposition; Dec 7–10, 2024; San Diego, US.
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