Clinical development of asciminib (ABL001) in chronic myeloid leukemia (CML): A randomized phase 3 study vs. bosutinib.

TPS7081Background: Several tyrosine kinase inhibitors (TKIs) targeting the BCR-ABL1 ATP-binding site are available to treat CML. However, new options are needed for patients (pts) with resistance/intolerance to these TKIs or who do not achieve treatment goals with them. Asciminib is a novel, potent and specific BCR-ABL1 inhibitor that targets the myristoyl pocket (Wylie, Nature 2017). Due to its distinct binding site, asciminib maintains activity against BCR-ABL1 mutants that confer resistance to ATP-binding site TKIs and offers the possibility for combination therapy with these TKIs. It therefore has the potential to address unmet needs in CML, including use in pts for whom ATP-binding site TKIs have failed or for combination with these TKIs in earlier lines, and in Philadelphia chromosome–positive acute lymphoblastic leukemia. In an ongoing phase 1 study in pts with resistance/intolerance to ≥ 2 TKIs (Hughes, Blood 2016 [abst 625]), asciminib has been well tolerated; 42% of pts achieved a major molecula...