In a phase III study published in Blood, asciminib was associated with higher rates of major molecular response (MMR) than bosutinib in patients with chronic myeloid leukemia in chronic phase (CP-CML) who had been previously treated with at least two tyrosine kinase inhibitors (TKIs).
Asciminib is a first-in-class allosteric inhibitor specifically targeting the ABL myristoyl pocket (STAMP), which the authors noted makes the agent poised “to transform care in this population through its novel mechanism of action, [given its] potential to overcome resistance or intolerance to approved TKIs.”
The study included 233 patients with CP-CML who had experienced either treatment failure or intolerance to their most recent TKI. The most common prior TKIs were dasatinib (84.1%), imatinib (82.8%), and nilotinib (68.7%).
Patients were randomly assigned to receive either asciminib 40 mg twice daily (n = 157) or bosutinib 500 mg once daily (n = 76).
After 24 weeks on study, 97 asciminib-treated patients (61.8%) were still on treatment, compared with 22 bosutinib-treated patients (28.9%). The authors reported that a higher proportion of patients in the bosutinib arm had discontinued therapy (37.6% vs. 71.1%).
The rate of MMR was 25.5% in the asciminib group and 13.2% in the bosutinib group (P = 0.029). The authors also noted that more patients in the asciminib group had BCR-ABL1IS (49.0% vs. 23.7% for bosutinib), and cumulative incidence of MMR was 25.0% vs. 12.0% in the asciminib and bosutinib groups, respectively.
In terms of safety, asciminib was associated with fewer grade ≥3 adverse events (AEs; 50.6% vs. 60.5%) and fewer AEs that led to discontinuation of treatment (5.8% vs. 21.1%).