A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs bosutinib in CML after 2 or more prior TKIs

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

Research output: Contribution to journalArticlepeer-review

103 Scopus citations


Patients with chronic myeloid leukemia in chronic phase (CML-CP) resistant/intolerant to ≥2 tyrosine kinase inhibitors (TKIs) are at high risk of experiencing poor outcomes because of disease biology and inadequate efficacy and/or safety of current therapies. Asciminib, a first-in-class BCR-ABL1 inhibitor Specifically Targeting the ABL Myristoyl Pocket (STAMP), has the potential to overcome resistance/intolerance to approved TKIs. In this phase 3, open-label study, patients with CML-CP previously treated with ≥2 TKIs were randomized (2:1) to receive asciminib 40 mg twice daily vs bosutinib 500 mg once daily. Randomization was stratified by major cytogenetic response (MCyR) status at baseline. The primary objective was to compare the major molecular response (MMR) rate at week 24 for asciminib vs bosutinib. A total of 233 patients were randomized to asciminib (n = 157) or bosutinib (n = 76). Median follow-up was 14.9 months. The MMR rate at week 24 was 25.5% with asciminib and 13.2% with bosutinib. The difference in MMR rate between treatment arms, after adjusting for MCyR at baseline, was 12.2% (95% confidence interval, 2.19-22.30; 2-sided P =.029). Fewer grade ≥3 adverse events (50.6% vs 60.5%) and adverse events leading to treatment discontinuation (5.8% vs 21.1%) occurred with asciminib than with bosutinib. The study showed a superior efficacy of asciminib compared with that of bosutinib, together with a favorable safety profile. These results support the use of asciminib as a new therapy in patients with CML-CP who are resistant/intolerant to ≥2 prior TKIs. This trial was registered at www.clinicaltrials.gov as #NCT03106779.

Original languageEnglish (US)
Pages (from-to)2031-2041
Number of pages11
Issue number21
StatePublished - Nov 25 2021

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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