Hughes TP, Mauro MJ, Cortes JE, et al. - In order to determine the safety as well as the antileukemic activity of asciminib (an allosteric inhibitor) in patients with Philadelphia chromosome–positive leukemia, researchers undertook this phase 1, dose-escalation study with 141 patients with chronic-phase and 9 with accelerated-phase chronic myeloid leukemia (CML) exhibiting resistance to or unacceptable side effects from at least two prior ATP-competitive tyrosine kinase inhibitors (TKIs). They looked for the maximum tolerated dose or the recommended dose (or both) of asciminib (primary objective). The participants were administered asciminib once or twice daily (at doses of 10 to 200 mg) and were observed for a median duration of 14 months. The maximum tolerated dose of asciminib was not reached. Findings revealed the activity of asciminib in heavily pretreated patients suffering from CML who showed resistance to or unacceptable side effects from TKIs, including cases with ponatinib failure and cases with a T315I mutation.