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

被引：1

作者：

Qi, Junyuan ^{[1
]}

Choi, Ilseung ^{[2
,9
]}

Ota, Shuichi ^{[3
]}

Ichikawa, Satoshi ^{[4
]}

Fujishima, Naohito ^{[5
]}

Iida, Hiroatsu ^{[6
]}

Sugiura, Isamu ^{[7
]}

Sugiura, Koichi ^{[8
]}

Murata, Yasuharu ^{[8
]}

Inoue, Hiroyuki ^{[8
]}

Ohwada, Shoichi ^{[8
]}

Wang, Jianxiang ^{[1
]}

机构：

[1] Chinese Acad Med Sci & Peking Union Med Coll, Inst Hematol & Blood Dis Hosp, Tianjin, Peoples R China

[2] Natl Hosp Org Kyushu Canc Ctr, Fukuoka, Japan

[3] Sapporo Hokuyu Hosp, Sapporo, Japan

[4] Tohoku Univ Hosp, Sendai, Japan

[5] Noshiro Kousei Med Ctr, Noshiro, Akita, Japan

[6] Natl Hosp Org Nagoya Med Ctr, Nagoya, Japan

[7] Toyohashi Hematol Oncol Clin, Toyohashi, Aichi, Japan

[8] Daiichi Sankyo Co Ltd, Tokyo, Japan

[9] Natl Hosp Org Kyushu Canc Ctr, 3-1-1 Notame,Minami Ku, Fukuoka, Fukuoka 8111395, Japan

来源：

CLINICAL PHARMACOLOGY IN DRUG DEVELOPMENT | 2024年 / 13卷 / 05期

关键词：

acute myeloid leukemia; FLT3; inhibitor; FLT3-ITD mutation; pharmacokinetics; quizartinib;

D O I：

10.1002/cpdd.1353

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：560 / 571

页数：12