Asciminib in combination with imatinib, nilotinib, or dasatinib in patients with chronic myeloid leukemia in chronic or accelerated phase: phase 1 study final results
Data from in vitro and animal studies suggest that asciminib, the first BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket (STAMP), synergizes with adenosine triphosphate (ATP)-competitive tyrosine kinase inhibitors (TKIs) to prevent emergence of and overcome resistance. Combination therapy may provide new treatment options for patients with chronic myeloid leukemia (CML) with suboptimal responses to ATP-competitive TKI monotherapy. Preliminary analysis of asciminib combined with nilotinib, imatinib, or dasatinib in a phase 1 dose-escalation study suggested promising efficacy and safety for patients with CML in chronic phase or accelerated phase treated with prior ATP-competitive TKIs; herein, we present final results from the 3 combination therapy arms. Asciminib, in combination with ATP-competitive TKIs, demonstrated rapid efficacy offset by a decreased tolerability compared with asciminib monotherapy. Based on these safety, tolerability, and preliminary efficacy results, asciminib 40 mg twice daily (BID) plus nilotinib 300 mg BID, asciminib 40 or 60 mg once daily (QD) plus imatinib 400 mg QD, and asciminib 80 mg QD plus dasatinib 100 mg QD were identified as recommended doses for expansion. The maximum tolerated dose was reached at asciminib 60 mg QD plus imatinib 400 mg QD and was not reached with asciminib plus nilotinib or dasatinib.
Authors
- Jörge E. Cortes (ORCID: https://orcid.org/0000-0002-8636-1071)
- Michael J. Mauro (ORCID: https://orcid.org/0000-0002-2251-4032)
- Jeroen J. W. M. Janssen (ORCID: https://orcid.org/0000-0001-9567-1955)
- Yeow Tee Goh (ORCID: https://orcid.org/0000-0002-7069-0997)
- Meng Cao (ORCID: https://orcid.org/0000-0002-3338-304X)
- Koji Sasaki (ORCID: https://orcid.org/0000-0002-9140-0610)
- Andreas Hochhaus (ORCID: https://orcid.org/0000-0003-0626-0834)
- Philipp le Coutre (ORCID: https://orcid.org/0000-0003-4532-1097)
- Nathalie Pognan
- Timothy P. Hughes (ORCID: https://orcid.org/0000-0002-0910-3730)
- Delphine Réa (ORCID: https://orcid.org/0000-0001-5379-7461)
- Matthias Hoch (ORCID: https://orcid.org/0009-0005-1033-2716)
- Daniel J. DeAngelo (ORCID: https://orcid.org/0000-0001-7865-2306)
- Gessamí Sánchez-Ollé
- Hironobu Minami (ORCID: https://orcid.org/0000-0001-8630-9145)
- Massimo Breccia (ORCID: https://orcid.org/0000-0003-1163-6162)
- Michael C. Heinrich (ORCID: https://orcid.org/0000-0003-3790-0478)
- Fabian Lang (ORCID: https://orcid.org/0000-0003-2890-029X)
Institutions
- Goethe University Frankfurt (DE)
- Novartis (Switzerland) (CH)
- Memorial Sloan Kettering Cancer Center (US)
- The University of Texas MD Anderson Cancer Center (US)
- Radboud University Nijmegen (NL)
- Oregon Health & Science University (US)
- Singapore General Hospital (SG)
- Policlinico Umberto I (IT)
- Radboud University Medical Center (NL)
- Portland VA Medical Center (US)
- Augusta University Health (US)
- Kobe University Hospital (JP)
- Novartis (France) (FR)
- Dana-Farber Cancer Institute (US)
- University Hospital Frankfurt (DE)
- Jena University Hospital (DE)
- South Australian Health and Medical Research Institute (AU)
- Hôpital Saint-Louis (FR)
- VA Portland Health Care System (US)
- The University of Adelaide (AU)
- Charité - Universitätsmedizin Berlin (DE)
Publication Details
- Journal
- Leukemia
- Published
- 2025-04-09
- DOI
- https://doi.org/10.1038/s41375-025-02592-9
- Citations
- 9
- Primary Topic
- Chronic Myeloid Leukemia Treatments
- Type
- article
- Field-Weighted Citation Impact
- 15.93
Funders
- Novartis
- Novartis Pharmaceuticals Corporation