Highlights from

ASH 2020

62nd Annual Meeting & Exposition of the American Society of Hematology

Virtual 5 - 8 December 2020

First-in-class STAMP inhibitor superior to bosutinib in chronic phase CML

ASCEMBL is the first controlled study comparing different tyrosine kinase inhibitors (TKIs) for resistant/intolerant patients with chronic myeloid leukaemia (CML). Asciminib, a first-in-class STAMP inhibitor, demonstrated statistically significant and clinically meaningful superior efficacy compared with bosutinib and a favourable safety profile. According to the authors, their results support the use of asciminib as a new treatment option in CML, particularly in patients with resistance/intolerance to ≥2 prior TKIs.

All approved TKIs bind to the ATP site of the BCR-ABL1 oncoprotein. Current therapies for patients with resistance or intolerance to ≥2 TKIs are limited by either modest efficacy, safety concerns, or both. Asciminib is a first-in-class STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor, so having a new mechanism of action. Bosutinib is the only second-generation ATP-competitive TKI, that demonstrated clinical efficacy in prospective clinical trials, both in patients with newly diagnosed CML and in patients with CML who received ≥2 prior TKIs. In a previous phase 1 study, asciminib monotherapy showed clinical activity in heavily pretreated patients with CML. Based on this finding, the question was if asciminib could provide superior efficacy to bosutinib beyond second line of treatment [1].

In the open-label, phase 3 study presented by Dr Andreas Hochhaus (Klinik für Innere Medizin II, Germany), 233 adult patients with CML in the chronic phase, previously treated with ≥2 TKIs, were randomised 2:1 to asciminib 40 mg twice daily or bosutinib 500 mg once daily. After a median follow-up of 14.9 months, median duration of exposure was 43.4 weeks (range 0.1-129.9) for asciminib and 29.2 weeks (range 1.0-117.0) for bosutinib; median relative dose intensity was 99.7% (87-100) and 95.4% (74-100).

The major molecular response (MMR) rate at 24 weeks was 25.5% with asciminib and 13.2% with bosutinib, meeting the primary objective (2-sided P=0.029). Grade ≥3 adverse events (AEs) occurred in 50.6% of patients receiving asciminib and in 60.5% of patients receiving bosutinib. Less patients discontinued treatment due to AEs with asciminib (5.8%) than with bosutinib (21.1%).

The investigators concluded that BCR-ABL1 remains the key driver of CML, even in patients beyond second line. Asciminib demonstrated a favourable benefit-risk profile in this patient population by its unique ability to specifically target the ABL myristoyl pocket.

  1. Hochhaus A, et al. Efficacy and Safety Results from ASCEMBL, a Multicenter, Open-Label, Phase 3 Study of Asciminib, a First-in-Class STAMP Inhibitor, vs Bosutinib (BOS) in Patients (Pts) with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Previously Treated with ≥2 Tyrosine Kinase Inhibitors (TKIs). 62nd ASH Annual Meeting, December 5-8, 2020. Abstract LBA-4.

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