Multinational randomized phase 1b trial of olverembatinib after failure of tyrosine kinase inhibitors for CML or Ph+ ALL

Patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) resistant or intolerant to BCR-ABL1 tyrosine kinase inhibitors (TKIs) have limited treatment options. Olverembatinib is a novel, orally administered, third-generation BCR-BL1 TKI which is approved in China but has not been tested in non-Chinese patients. A multicenter phase 1b trial in the USA and Russia evaluated olverembatinib for CML or Ph+ ALL after failure of at least two TKIs. The trial included 80 patients who were randomized to olverambatinib 30, 40, 0r 50 mg every other day. The trial found favorable pharmacokinetics compatible with alternate-dosing. Olverembatinib was generally well tolerated, and demonstrated strong antileukemic activity, including in patients with treatment failure with ponatinib and/or asciminib. The authors conclude that olverembatinib may be a viable treatment option for patients after failure of two or more TKIs, including third-generation agents.