Population pharmacokinetic and exposure-response analysis to support a dosing regimen of CPX-351 (NS-87) in Japanese adult and pediatric patients with untreated high-risk acute myeloid leukemia.

Abstract

CPX-351 (NS-87; Vyxeos®) has a characteristic liposomal formulation and contains cytarabine and daunorubicin at a 5:1 molar ratio, which demonstrates synergistic activity in both in vitro and in vivo animal models. It has been approved in several countries for the treatment of newly diagnosed, therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC). Since there are very few Asian patients, especially Japanese adult and pediatric patients, only a small clinical study has been conducted in Japanese adult patients and no study in Japanese pediatric patients. Therefore, we need to continue collecting data to ensure efficacy, especially in Japan. The objectives of this study were to evaluate the exposure and efficacy of CPX-351 in adult and pediatric Japanese patients. For these purposes, population pharmacokinetic and exposure-response analysis was conducted based on the established model/analysis using non-Japanese data by incorporating the newly obtained results of a Japanese clinical trial. No significant differences in pharmacokinetic exposure and efficacy were observed between non-Japanese adult patients and Japanese adult or pediatric patients. This information supports CPX-351 as a treatment option for untreated Japanese t-AML/AML-MRC patients on the basis of efficacy and safety when referred to the evidence from non-Japanese subjects.