CML-395 Efficacy and Safety Results From ASCEMBL, a Phase III Study of Asciminib vs. Bosutinib in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP) After ≥2 Prior Tyrosine Kinase Inhibitors (TKIs): Week 96 Update

Delphine Réa, Andreas Hochhaus, Michael J. Mauro, Yosuke Minami, Elza Lomaia, Sergey Voloshin, Anna Turkina, Dong Wook Kim, Jane F. Apperley, Jorge E. Cortes, Andre Abdo, Laura Marie Fogliatto, Dennis Dong Hwan Kim, Philipp le Coutre, Susanne Saussele, Mario Annunziata, Timothy P. Hughes, Naeem Chaudhri, Lynette Chee, Valentin García-GutiérrezKoji Sasaki, Shruti Kapoor, Alex Allepuz, Sara Quenet, Véronique Bédoucha, Carla Boquimpani

Research output: Contribution to journalArticlepeer-review

Abstract

Context: Asciminib is the first BCR::ABL1 inhibitor to Specifically Target the ABL Myristoyl Pocket (STAMP). In the ASCEMBL primary analysis, among patients with CML-CP after ≥2 prior TKIs, asciminib resulted in improved major molecular response (MMR, 25.5% vs. 13.2%) at week 24 and fewer grade ≥3 adverse events (AEs) or AEs leading to treatment discontinuations compared with bosutinib. After a median follow-up of 2.3 years, we report updated efficacy and safety results (data cutoff: October 6, 2021). Objective: To compare the MMR rate at week 96 with asciminib vs. bosutinib. Design: A phase III, multicenter, open-label study of adults with CML-CP after ≥2 prior TKIs randomized 2:1 to asciminib 40 mg twice daily or bosutinib 500 mg once daily and stratified by baseline major cytogenetic response (MCyR). Results: In total, 233 patients were randomized to receive asciminib (n=157) or bosutinib (n=76). At data cutoff, treatment was ongoing in 84 (53.5%) and 15 (19.7%) patients, respectively; the most common reason for discontinuation was lack of efficacy in 38 (24.2%) and 27 (35.5%) patients, respectively. The key secondary objective was met; MMR rate at week 96 was higher with asciminib (37.6%) than with bosutinib (15.8%). The difference after adjusting for MCyR was 21.7% (95% CI, 10.5%–33.0%; 2-sided P=.001). At week 96, more patients receiving asciminib than bosutinib had BCR::ABL1IS ≤1% (45.1% vs. 19.4%). Responses were durable, with a probabilities (95% CI) of maintaining MMR and BCR::ABL1IS ≤1% for ≥72 weeks of 96.7% (87.4%–99.2%) and 94.6% (86.2%–97.9%), respectively, with asciminib and 92.9% (59.1%–99.0%) and 95.0% (69.5%–99.3%), respectively, with bosutinib. Median time to treatment failure was 24 months with asciminib and 6 months with bosutinib. Asciminib had longer duration of exposure (103.1 vs. 30.5 weeks) but fewer AEs leading to treatment discontinuation (7.7% vs. 26.3%) than bosutinib. Conclusions: After >2 years of follow-up, asciminib demonstrated durable responses by continuing to show superior efficacy and better safety/tolerability vs. bosutinib. MMR more than doubled with asciminib over bosutinib, and the difference in MMR rates increased between the 2 arms from 12.2% at week 24 to 21.7% at week 96. These results support the use of asciminib as a new CML therapy.

Original languageEnglish (US)
Pages (from-to)S295-S296
JournalClinical Lymphoma, Myeloma and Leukemia
Volume22
DOIs
StatePublished - Oct 2022

Keywords

  • ASCEMBL
  • CML
  • Phase III
  • TKI
  • Trial-in-Progress
  • asciminib

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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