主催: 第94回日本薬理学会年会
会議名: 第94回日本薬理学会年会
回次: 94
開催地: Sapporo
開催日: 2021/03/08 - 2021/03/10
Fms-like tyrosine kinase 3 (FLT3) mutations have been found in about 30% of acute myeloid leukemia (AML) cases, and the most common form of FLT3 mutation is internal tandem duplication (ITD) in the juxtamembrane domain, which is associated with poor prognosis.
In non-clinical studies, quizartinib clearly inhibited FLT3 signaling pathways in FLT3-ITD–mutated human AML cells, leading to potent growth inhibition. When quizartinib was given to mice bearing human FLT3-ITD AML MV4-11 cells, the tumor regression was observed. In addition, quizartinib inhibited the viability of the on midostaurin-resistant human FLT3-ITD AML MOLM-14 cells, and exerted potent in vivo anti-tumor activity.
Quizartinib showed clinical benefit in patients with FLT3-ITD–mutated relapsed/refractory AML in phase III QuANTUM-R trial (NCT02039726). Quizartinib significantly prolonged median survival time compared with salvage chemotherapy (6.2 months vs 4.7 months; HR = 0.76 [95% CI, 0.58–0.98; P = 0.0177]). The most common TEAEs were thrombocytopenia, nausea and anemia. A phase III QuANTUM-First trial (NCT02668653) in patients with newly diagnosed FLT3-ITD–mutated AML is now ongoing.
Non-clinical and clinical profile of quizartinib suggests its potential for further clinical investigation of optimum treatment sequence with FLT3 inhibitors for the AML patients.
