ASH20: ASCEMBL Trials Shows Asciminib Effectiveness as Third-Line Treatment for CML

By Mary Ellen Schneider

The STAMP inhibitor asciminib appears safe and effective as third-line treatment for patients with chronic myeloid leukemia (CML) in chronic phase, according to findings from the phase 3 ASCEMBL trial.

The results, which were presented as part of a late breaking abstract session at the annual meeting of the American Society of Hematology, demonstrated that asciminib was nearly twice as effective as a standard-of-care treatment regimen in achieving a major molecular response.

Asciminib is a first-in-class STAMP inhibitor, that works by specifically targeting the ABL myristoyl pocket, a different mechanism than seen with tyrosine kinase inhibitors (TKIs).

“The ASCEMBL data support the use of asciminib as a new treatment option in CML, particularly in patients with resistance or intolerance to at least two TKIs,” said Andreas Hockhaus, MD, of University Hospital, Jena, in Germany, who presented the results of the study.

Dr. Hockhaus said that Novartis, which manufacturers asciminib, plans to submit the drug for approval in the United States and Europe in early 2021.

The randomized controlled trial enrolled 233 patients with Philadelphia chromosome-positive CML in chronic phase who had previously been treated with two or more TKIs. Patients were randomized to receive either asciminib (40 mg twice daily) or bosutinib (500 mg once daily) for 24 weeks (Abstract LBA-4). The median follow up was 14.9 months.

The study met its primary objective of major molecular response (MMR) at 24 weeks. MMR was achieved by 25.5% of patients receiving asciminib at 24 weeks, compared with 13.2% of patients receiving bosutinib. The common treatment difference after adjusting for MCyR status at baseline was 12.2% (95% CI, 2.19-22.3; 2-side P=0.029).

The median duration of exposure was 43.3 weeks for asciminib and 29.2 weeks for bosutinib.

“A consistent treatment effect was observed across the subgroups assessed, supporting the benefit of asciminib treatment,” Dr. Hockhaus said. “Notably MMR rates at 24 weeks were consistently higher for asciminib versus bosutinib across all lines of prior therapy.”

The rate of complete cytogenetic response at 24 weeks was 40.8% for asciminib and 24.2% for bosutinib. Additionally, a higher percentage of patients achieved MR4 and MR4.5 with acsiminib at 24 weeks.

Adverse events of at least grade 3 were observed in 50.6% of patients receiving asciminib, compared with 60.5% of patients receiving bosutinib.

Researchers also analyzed newly emerging BCR-ABL1 mutations. Among 17 patients on asciminib who had baseline mutations, three patients developed new ATP binding site mutations during the study. Four patients without mutations at baseline developed mutations on asciminib, two at the ATP binding site and two at the myristoyl binding pocket. In the bosutinib arm, nine patients had mutations at the start of treatment, but none developed mutations during the study. “Conclusions on the impact of mutations cannot be made due to their low incidence and heterogeneity,” Dr. Hockhaus said.

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