On the Horizon: Asciminib, a New Drug for Treating R/R CML

On the Horizon: Asciminib, a New Drug for Treating R/R CML

The investigational drug asciminib (being developed by Novartis) may become the new kid on the block for the treatment of chronic phase chronic myeloid leukemia (CMP-CP) for patients who have relapsed on or are refractory to at least two prior tyrosine kinase inhibitors (TKIs).

New results from the ASCEMBL study (NCT03106779) show that patients who received asciminib, which works differently from currently approved therapies for CML-CP, achieved better responses compared to bosutinib (Bosulif) as third-line therapy.

“The ASCEMBL study opens a new chapter for CML, proving comparatively superior efficacy and excellent safety for a new class of ABL inhibitors,” co-investigator Michael J. Mauro, MD, from Memorial Sloan Kettering Cancer Center, New York City, told Medscape Medical News.

The trial was presented as a late-breaking abstract at the American Society of Hematology (ASH) 2020 virtual meeting.

Asciminib is a first-of-a-kind STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor that works differently from currently approved TKIs, which are ATP-competitive ABL inhibitors.

Five TKIs have been approved by the US Food and Drug Administration to treat CML: imatinib (Gleevec; generics), nilotinib (Tasigna), dasatinib (Sprycel), bosutinib, and ponatinib (Iclusig).

All of them inhibit BCR/ABL tyrosine kinase by binding to the ATP-binding pocket.

Most patients with TKI resistant disease develop mutations in the ATP-binding pocket, explained Michael Jay Styler, MD, associate professor at Fox Chase-Temple University Hospital Bone Marrow Transplant Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.

By inactivating the protein through binding outside the ATP site, asciminib is a novel BCR-ABL inhibitor and may be a superior alternative to further traditional TKIs. “This agent promises to be an important addition to our treatment armamentarium for CML,” Styler told Medscape Medical News.

Another expert agreed. “Although we have many excellent therapies for CML, having a new medication that targets BCR-ABL in a novel way is still welcome to help us better care for CML patients,” Gabriela S. Hobbs, MD, told Medscape Medical News. Hobbs is the clinical director of leukemia services at Boston’s Mass General Cancer Center, Massachusetts.

Patients in this study had previously been receiving at least two different types of TKIs. “The responses looked very encouraging for this group of heavily pretreated patients. Although CML patients do very well on current therapies, those that don’t get a response with TKI remain a difficult clinical challenge,” Hobbs said.

“This is the first study comparing asciminib to a TKI directly (in this case bosutinib) and it showed safety as well as preliminary evidence of efficacy. I look forward to seeing additional studies with this promising drug and to have a new drug to add to the CML arsenal,” she added.

Identifying Patients Who Will Benefit From Asciminib

Patients with CML are currently sequenced through more than one second-generation TKI, Mauro commented. “If imatinib and a second-generation TKI have not served a pat

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