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

Author:

Qi Junyuan1,Choi Ilseung2,Ota Shuichi3,Ichikawa Satoshi4,Fujishima Naohito5,Iida Hiroatsu6,Sugiura Isamu7,Sugiura Koichi8,Murata Yasuharu8,Inoue Hiroyuki8,Ohwada Shoichi8,Wang Jianxiang1

Affiliation:

1. Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Tianjin China

2. National Hospital Organization Kyushu Cancer Center Fukuoka Japan

3. Sapporo Hokuyu Hospital Sapporo Japan

4. Tohoku University Hospital Sendai Japan

5. Noshiro Kousei Medical Center Akita Japan

6. National Hospital Organization Nagoya Medical Center Nagoya Japan

7. Toyohashi Hematology Oncology Clinic Aichi Japan

8. Daiichi Sankyo Co., Ltd Tokyo Japan

Abstract

AbstractQuizartinib 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.

Publisher

Wiley

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