Effects of a High-Fat Meal on the Pharmacokinetics of Olverembatinib in Patients With Chronic Myeloid Leukemia.

Olverembatinib is approved in China to treat patients with chronic- or accelerated-phase chronic myeloid leukemia (CML-CP or CML-AP) with T315I mutations and CML-CP that is resistant and/or intolerant to first- and second-generation tyrosine kinase inhibitors. The objective of this study was to determine the effects of a high-fat meal on the pharmacokinetics of olverembatinib in patients with CML. Twelve participants were enrolled and received olverembatinib treatment over two periods, with a washout of 7 days between consecutive doses. Pharmacokinetics and safety were assessed in all participants. When olverembatinib was administered with a high-fat meal, the maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve from time 0 to infinity (AUC0-∞) of olverembatinib increased by 105.74% and 69.74%, respectively, compared to fasting conditions. The median time to maximum plasma concentration (Tmax) of olverembatinib was not affected when it was administered with a high-fat meal, and the geometric mean terminal plasma half-life (t1/2) was comparable between high-fat meal and preprandial conditions (26.8 vs. 31.1 h). The safety profile of olverembatinib was consistent with observations from previous studies; all treatment-related adverse events were mild, and no serious adverse event was reported. These results indicate that consumption of a high-fat meal 30 min before administering olverembatinib can increase its plasma exposure to some extent.