Related Experiment Video
Updated: Oct 23, 2025
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs bosutinib in CML after 2 or more prior
Delphine Réa1, Michael J Mauro2, Carla Boquimpani3,4
1DMU Hématologie, Hôpital Saint-Louis, Paris, France.
Abstract:
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.
Insights
Asciminib demonstrated superior efficacy and a favorable safety profile compared to bosutinib in patients with chronic myeloid leukemia resistant to prior therapies. This finding supports asciminib as a new treatment option for difficult-to-treat CML-CP.
Area of Science:
- Hematology
- Oncology
- Pharmacology
Background:
- Chronic myeloid leukemia in chronic phase (CML-CP) resistant or intolerant to multiple tyrosine kinase inhibitors (TKIs) presents significant treatment challenges.
- Limited therapeutic options exist for patients with advanced CML-CP, driving the need for novel treatment strategies.
Purpose of the Study:
- To evaluate the efficacy and safety of asciminib compared to bosutinib in patients with CML-CP previously treated with two or more TKIs.
- To determine if asciminib, a BCR-ABL1 inhibitor targeting the ABL myristoyl pocket (STAMP), can overcome resistance to existing TKIs.
Main Methods:
- A phase 3, open-label, randomized study comparing asciminib (40 mg BID) with bosutinib (500 mg QD) in 233 CML-CP patients pre-treated with ≥2 TKIs.
- Patients were stratified by major cytogenetic response (MCyR) at baseline, with the primary endpoint being the major molecular response (MMR) rate at week 24.
Main Results:
- Asciminib achieved a significantly higher MMR rate at week 24 (25.5%) compared to bosutinib (13.2%), with a difference of 12.2% (P = .029).
- Asciminib demonstrated a more favorable safety profile, with fewer grade ≥3 adverse events (50.6% vs 60.5%) and fewer treatment discontinuations due to adverse events (5.8% vs 21.1%).
Conclusions:
- Asciminib shows superior efficacy and a better safety profile than bosutinib in CML-CP patients resistant or intolerant to ≥2 prior TKIs.
- These findings support asciminib as a valuable new therapeutic option for patients with advanced, difficult-to-treat CML-CP.
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