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Clinical Trial
. 2024 May;13(5):560-571.
doi: 10.1002/cpdd.1353. Epub 2024 Jan 29.

Safety and Pharmacokinetics of Quizartinib Combination Therapy With Standard Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia: Results from Two Phase 1 Trials in Japan and China

Junyuan Qi  1 , Ilseung Choi  2 , Shuichi Ota  3 , Satoshi Ichikawa  4 , Naohito Fujishima  5 , Hiroatsu Iida  6 , Isamu Sugiura  7 , Koichi Sugiura  8 , Yasuharu Murata  8 , Hiroyuki Inoue  8 , Shoichi Ohwada  8 , Jianxiang Wang  1
Affiliations
Clinical Trial

Safety and Pharmacokinetics of Quizartinib Combination Therapy With Standard Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia: Results from Two Phase 1 Trials in Japan and China

Junyuan Qi et al. Clin Pharmacol Drug Dev. 2024 May.

Abstract

Quizartinib is a potent, oral, second-generation, selective type II FMS-like receptor tyrosine kinase 3 (FLT3) inhibitor. It has shown improved overall survival in a randomized, multinational, Phase 3 (QuANTUM-First) study in patients with FLT3-internal tandem duplication (ITD)-positive newly diagnosed acute myeloid leukemia. We conducted 2 Phase 1b studies in Japan and China to evaluate the safety, pharmacokinetics, and efficacy of quizartinib in combination with standard induction and consolidation chemotherapy in patients with newly diagnosed acute myeloid leukemia. Quizartinib was started at a dose level of 20 mg/day and then escalated to 40 mg/day, the dose used in the Phase 3 study. Seven patients were enrolled according to the 3 + 3 dose-escalation method in each study, including 3 patients who were FLT3-ITD positive. No dose-limiting toxicities were observed at dose levels up to 40 mg/day in both studies. Grade 3 or higher, quizartinib-related, treatment-emergent adverse events included febrile neutropenia, hematologic toxicities, and infections. QT prolongation on electrocardiogram was observed in 5 patients. The pharmacokinetics of quizartinib and its metabolite AC886 were similar between the studies and consistent with previous findings in the United States. We confirmed the tolerability of Japanese and Chinese patients to the dose of quizartinib and chemotherapy regimens used in the QuANTUM-First study.

Keywords: FLT3 inhibitor; FLT3‐ITD mutation; acute myeloid leukemia; pharmacokinetics; quizartinib.

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