Olverembatinib After Failure of Tyrosine Kinase Inhibitors, Including Ponatinib or Asciminib: A Phase 1b Randomized Clinical Trial.

作者：E. Jabbour, V. Oehler, Paul B. Koller, Omer Jamy, E. Lomaia, Anthony M. Hunter, O. Uspenskaya, S. Samarina, Sudipto Mukherjee, J. Cortes, Maria R. Baer, V. Zherebtsova, V. Shuvaev, A. Turkina, I. Davydkin, Huanshan Guo, Zi Chen, Tommy Fu, Lixin Jiang, Cunlin Wang, Hengbang Wang, Dajun Yang, Y. Zhai, Hagop M Kantarjian · 发表于：JAMA Oncology · 年份：2024 · DOI：10.1001/jamaoncol.2024.5157 · 被引用次数：32 · 研究领域：Medicine

Importance 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, which is approved in China, has only been tested in Chinese patients. Objective To assess the pharmacokinetics, safety, efficacy, and recommended dose of olverembatinib in patients with CML or Philadelphia chromosome-positive ALL resistant or intolerant to at least 2 TKIs. Design, Setting, and Participants This multicenter phase 1b randomized clinical trial was conducted from January 28, 2020, to January 2, 2024, with a median (range) follow-up of 48 (0-166) weeks. Patients with CML or Philadelphia chromosome-positive ALL were enrolled. This bridging study was performed in part to confirm that there are no racial differences in the pharmacokinetic profile of olverembatinib. Interventions Patients were randomly assigned to 30, 40, or 50 mg of olverembatinib orally every other day in 28-day cycles. Main Outcomes and Measures Pharmacokinetic profile of olverembatinib. Results Of 80 included patients, 46 (58%) were male, and the median (range) age was 54.0 (21-80) years. The pharmacokinetic profile of olverembatinib was compatible with alternate-day dosing and similar to that in Chinese patients. Based on investigators' assessments, 60 patients (75%) experienced at least 1 treatment-related adverse event; 32 (40%) experienced gra...