FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) mutations in patients with acute myeloid leukemia (AML) are associated with early relapse and poor survival. This multicenter, single-arm, two-stage phase 2 study (NCT02984995) was conducted to evaluate the efficacy and safety of quizartinib hydrochloride (initial dose 20/30 mg/day), an oral, highly potent, selective FLT3 inhibitor in Japanese patients (median age 65 years) with FLT3-ITD positive relapsed/refractory (R/R) AML. The composite complete remission (CRc) rate (primary endpoint) was 53.8% (90% confidence interval 36.2-70.8%) for evaluable patients in the efficacy analysis set. The median duration of CRc and overall survival was 16.1 weeks and 34.1 weeks, respectively. The most frequent treatment-emergent adverse events (TEAEs) were febrile neutropenia (43.2%), platelet count decreased (37.8%), and QT prolonged (35.1%). Two (5.4%) patients experienced TEAEs associated with treatment discontinuation. All serious TEAEs (45.9%), except febrile neutropenia (16.2%), were reported in ≤ 2 patients. The incidence of QTcF 451-480 ms and 481-500 ms was 37.8% and 2.7%, respectively. No QTcF > 500 ms, events of torsade de pointes or arrhythmia with clinical symptoms were reported. Quizartinib monotherapy was well tolerated and resulted in clinically meaningful reductions in blast count in Japanese patients with FLT3-ITD R/R AML.

中文翻译：

---

一项开放标签的2期研究显示，奎扎替尼在日本FLT3-ITD阳性复发或难治性急性髓性白血病患者中的疗效和安全性。

急性髓细胞性白血病（AML）患者中，FMS样酪氨酸激酶3（FLT3）内部串联重复（ITD）突变与早期复发和生存不良有关。这项多中心，单臂，两阶段的2期研究（NCT02984995）旨在评估盐酸奎扎替尼（初始剂量20/30 mg /天）（一种口服，高效，选择性FLT3抑制剂）在日本患者中的疗效和安全性。 （中位年龄65岁）患有FLT3-ITD阳性复发/难治性（R / R）AML。在疗效分析集中，可评估患者的复合完全缓解（CRc）率（主要终点）为53.8％（90％置信区间36.2-70.8％）。CRc的中位持续时间和总生存期分别为16.1周和34.1周。最常出现的治疗紧急不良事件（TEAE）是发热性中性粒细胞减少（43.2％），血小板计数减少（37.8％），QT延长（35.1％）。2名（5.4％）患者经历了与停药相关的TEAE。据报道，除发热性中性粒细胞减少症（16.2％）外，所有严重TEAE（45.9％）均≤2例。QTcF 451-480 ms和481-500 ms的发生率分别为37.8％和2.7％。没有QTcF> 500 ms，有临床症状的足尖扭转或心律不齐的报道。Quizartinib单药治疗耐受性良好，并导致日本患有FLT3-ITD R / R AML的患者的胚泡计数减少具有临床意义。分别为7％。没有QTcF> 500 ms，有临床症状的足尖扭转或心律不齐的报道。Quizartinib单药治疗耐受性良好，并导致日本患有FLT3-ITD R / R AML的患者的胚泡计数减少具有临床意义。分别为7％。没有QTcF> 500 ms，有临床症状的足尖扭转或心律不齐的报道。Quizartinib单药治疗耐受性良好，并导致日本患有FLT3-ITD R / R AML的患者的胚泡计数减少具有临床意义。