asciminib + nilotinib

Asciminib + nilotinib is a combination therapy comprising asciminib, a first-in-class allosteric inhibitor of BCR–ABL1 (specifically targeting the ABL myristoyl pocket), and nilotinib, an ATP-competitive tyrosine kinase inhibitor. This drug combination is used in the treatment of chronic myeloid leukemia (CML). Asciminib binds to a site distinct from ATP, causing conformational changes in BCR–ABL1 that make activation less favorable, while nilotinib inhibits the ATP pocket directly. In combination, asciminib enhances the inhibitory effect of nilotinib by increasing its efficacy and lowering the dose required, potentially mitigating dose-dependent toxicities and preventing or overcoming resistance, particularly in patients with mutations such as T315I[1][2][3]. The combination is investigated in patients who have failed multiple previous tyrosine kinase inhibitors, showing rapid and substantial molecular responses in clinical trials, though tolerability may be modestly decreased compared to monotherapy[2][3][5].

Brand names

TasignaScemblix

Other names

asciminib + nilotinib