Olverembatinib, a tyrosine kinase inhibitor (TKI) approved in China, shows promising results in treating chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) patients resistant or intolerant to multiple TKIs, including ponatinib and asciminib. A recent phase 1b clinical trial, published in JAMA Oncology, evaluated the pharmacokinetics, safety, and efficacy of olverembatinib in non-Chinese patients.
The multicenter trial, conducted from January 2020 to January 2024, enrolled 80 adult patients with CML or Ph+ ALL who had failed at least two prior TKIs. Patients were randomly assigned to receive 30, 40, or 50 mg of olverembatinib orally every other day. The primary outcome measured was the pharmacokinetic profile of olverembatinib.
The study found that olverembatinib's pharmacokinetic profile was consistent with alternate-day dosing and similar to that observed in Chinese patients. The drug was generally well-tolerated, with the most common treatment-related adverse events being elevated blood creatine phosphokinase (39% all grades, 13% grade 3 or higher) and thrombocytopenia (29% all grades, 18% grade 3 or higher).
In evaluable patients with chronic-phase CML, 61% (95% CI, 46.1-74.2) achieved a complete cytogenetic response (CCyR), and 42% (95% CI, 29.6-55.9) achieved a major molecular response (MMR). Notably, cytogenetic and molecular responses were similar in patients with or without T315I mutations. Among patients previously treated with ponatinib, 58% achieved CCyR and 37% achieved MMR. In patients with asciminib resistance, 50% had CCyR and 33% had MMR.
"Olverembatinib may provide a viable new treatment option for patients after failure of two or more TKIs," the researchers concluded. The recommended phase 3 dose of olverembatinib is 30 mg every other day in patients without T315I variants. These findings suggest that olverembatinib could address the unmet need for effective therapies in patients with TKI-resistant CML and Ph+ ALL, offering a potential new treatment avenue for those who have exhausted other options.
