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ASH 2020 | Asciminib and bosutinib efficacy in CML-CP patients: a comparison study
Andreas Hochhaus, MD, Klinik für Innere Medizin II, Jena, Germany, discusses ASCEMBL, a Phase III study aiming to compare the safety and efficacy of asciminib and bosutinib (BOS) in previously treated patients with chronic myeloid leukemia in chronic phase (CML-CP). A 24-week rate of major molecular response, the primary endpoint of this study was met. The overall results favor the use of asciminib in CML-CP patients, as it produced a higher rate of major molecular response. It also performed better than bosutinib across other criteria, including complete cytogenetic response, deep molecular response and the duration of major molecular response. These findings suggest that asciminib may be an ideal third-line therapy for CML-CP patients. Other ongoing studies are aiming to evaluate its efficacy both as monotherapy and in combination with other tyrosine kinase inhibitors. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.
Transcript (edited for clarity)
Patients who failed two different tyrosine kinase inhibitors in CML in chronic phase require alternative treatments. We are happy with the current situation. We are able to treat about 40 to 50% of patients sufficiently with alternative tyrosine kinase inhibitors, but these produce, in most cases, side effects. Therefore, we were looking for a drug which has less side effects and is even more efficacious...
Patients who failed two different tyrosine kinase inhibitors in CML in chronic phase require alternative treatments. We are happy with the current situation. We are able to treat about 40 to 50% of patients sufficiently with alternative tyrosine kinase inhibitors, but these produce, in most cases, side effects. Therefore, we were looking for a drug which has less side effects and is even more efficacious. And with asciminib which has been tested in a Phase I study, we found such a drug, because asciminib is a very specific BCR-ABL inhibitor. It inhibits a myristoyl binding site of BCR-ABL, in contrast to all the other inhibitors which have been tested and used on the market so far, which are all ATP competitors.
Now, we have a new mode of action, and with this new mode of action we have a very specific BCR-ABL inhibitor, and the Phase I data we are encouraging, therefore Phase III was started, and the Phase III is called ASCEMBL. And this ASCEMBL trial compares the efficacy and safety of asciminib versus bosutinib. And the study is completed. It met the primary endpoint, which was the 24-week rate of MMR, major molecular response. And the data is significant. That means asciminib produced more major molecular responses at this early time point as compared to bosutinib, but also other markers, like complete cytogenetic response, and the deep molecular response, and the duration of major molecular response is advantageous for asciminib. And therefore, in my opinion, my conclusion out of this study is that asciminib is a very good new drug for a third-line treatment of CML.
Based on the results of ASCEMBL, I expect registration of this drug. That means we need it in the clinics and on the market. But new trials have started with this new endpoints and new patient populations. A study which adds asciminib to other tyrosine kinase inhibitors to improve the response to produce deep molecular response is ongoing, and other studies try to investigate asciminib as a monotherapy or in combination as a first-line drug. And in my personal opinion, asciminib may be an ideal first-line drug because it specifically inhibits BCR-ABL, therefore it’s even more active before any clonal evolution of the CML is ongoing. It works in third-line, but I expect an even better data in first-line use.
Research funding: Novartis, Incyte, Pfizer, Bristol Myers Squibb