Asciminib monotherapy in patients with BCR::ABL1 T315I-mutated chronic-phase chronic myeloid leukemia: phase 1 trial...

In chronic myeloid leukemia in chronic phase (CML-CP), BCR::ABL1^T315I commonly leads to treatment resistance, worse patient outcomes, and limited subsequent treatment options. By targeting the ABL1 myristoyl pocket, asciminib maintains activity against BCR::ABL1^T315I. We report final long-term safety, tolerability, and efficacy results with asciminib in 48 patients with T315I-mutated CML-CP who received asciminib 200 mg twice daily in the phase 1, nonrandomized trial (NCT02081378). After a median exposure of 3.5 years, 52.1% of patients continued to receive asciminib via posttrial access. Of 45 evaluable patients, 24 (53.3%) achieved major molecular response (MMR); 20 of 24 maintained or deepened their response by the cutoff. The Kaplan-Meier estimated proportion of patients maintaining their first MMR for at least 144 weeks (2.8 years) was 86% (95% CI: 71.9-100.0%). The safety profile showed no new or worsening safety signals. With 1.4 years' additional exposure since the previous analysis, the incidence of grade ≥3 adverse events (AEs) (60.4%) did not increase. Four patients (8.3%) discontinued due to AEs. The exposure-adjusted incidence rate of first all-grade AOEs was 4.4 cases per 100 patient-years. With up to approximately 6 years of exposure, this final analysis confirms asciminib as a treatment option for patients with T315I-mutated CML-CP.