Exploring Asciminib Monotherapy in CML-CP +/- T315I Mutations

Moshe Levy, MD, the director of Hematologic Malignancies Research at Texas Oncology- Baylor Charles A. Sammons Cancer Center, discusses the ongoing phase 3b study of single-agent asciminib for the treatment of patients with chronic myeloid leukemia in chronic phase (CML-CP) who may or may not harbor T315I mutations.

Asciminib is an investigational BCR-ABL1 inhibitor that directly targets STAMP. In early-phase studies, the agent demonstrated promising efficacy and safety in patients with CML-CP who were resistant or intolerant to other tyrosine kinase inhibitors (TKIs) having failed at least 2 prior lines of therapy.

The AIM2CML clinical trial (NCT04666259) is further investigating the efficacy and safety of the drug in this patient population.

Transcription:

0:08 | The big take home message here is that this is a tyrosine kinase inhibitor that works differently than our current tyrosine kinase inhibitors that are currently on the market. So, in the US, we have 5 commercially approved TKIs, imatinib [Gleevec] anlotinib [AL3818], dasatinib

[Sprycel], bosutinib [Bosulif], and ponatinib [Iclusig]. And these are all what's called ATP competitive TK eyes. And this is what's called an allosteric inhibitor. So, it has a completely different binding sites.

0:40 | I think what's most exciting about this particular therapy, actually, there's 2 things that I am particularly excited about. So, the first one is the profile of this drug seems to be fantastic in the preliminary data that has been seen so far. Furthermore, the efficacy is also fantastic. So, we have not seen any kinase domain mutations that confer resistance to this therapy. So, it makes it an attractive option for folks, you know, with the T315I mutation for which only ponatinib works in terms of TKIs currently available, but the tolerability profile, you know, and the efficacy profile lends itself to being used in a variety of resistant chronic myelogenous leukemias.

1:28 | Furthermore, and this is extrapolating further down the road. This mechanism of action can be complimentary with the use of these ATP competitive TKIs and hopefully the combination may lead to durability, and more people will be cured and be able to discontinue therapy.