Phase 2b study of two dosing regimens of quizartinib monotherapy in FLT3-ITD mutated, relapsed or refractory AML

Jorge E. Cortes, Martin S. Tallman, Gary J. Schiller, Denise Trone, Guy Gammon, Stuart L. Goldberg, Alexander E. Perl, Jean-Pierre Marie, Giovanni Martinelli, Hagop M. Kantarjian and Mark J. Levis

Key points

  • Quizartinib at 60-mg/day (vs 30-mg/day) was associated with higher overall response, survival, and bridge to transplant.

  • The benefit-risk profile of quizartinib in relapsed or refractory FLT3-ITD mutated AML warrants further evaluation of the 60-mg once daily dose.


This randomized, open-label, phase 2b study (NCT01565668) evaluated efficacy and safety of two dosing regimens of quizartinib monotherapy in patients with relapsed/refractory (R/R) FLT3-internal tandem duplication (ITD)–mutated acute myeloid leukemia (AML) who previously underwent transplant or one second-line salvage therapy. Patients (N=76) were randomized to 30- or 60-mg/day doses (escalations to 60 or 90 mg/day, respectively, permitted for lack/loss of response) of single-agent oral quizartinib dihydrochloride. Allelic frequency ≥10% was defined as FLT3-ITD mutated disease. Co-primary endpoints were composite complete remission (CRc) rates, and incidence of QT interval corrected by Fridericia’s formula (QTcF) >480 msec (grade 2 or greater). Secondary endpoints included overall survival (OS), duration of CRc, bridge to transplant, and safety. CRc rates were 47% in both arms, similar to earlier reports with higher quizartinib doses. Incidence of QTcF >480 msec was 11% and 17% and QTcF >500 msec was 5% and 3% in 30-mg and 60-mg arms, respectively; less than earlier reports with higher doses of quizartinib. Median OS (20.9 and 27.3 weeks), duration of CRc (4.2 and 9.1 weeks), and bridge to transplant rates (32% and 42%) were higher in 60-mg arm than in 30-mg arm. Dose escalation occurred in 61% and 14% of patients in 30-mg and 60-mg arms, respectively. This high clinical activity of quizartinib at the evaluated doses is consistent with previous reports with an improved safety profile. Need to dose-escalate more than half of patients who received quizartinib 30 mg also supports further investigation of treatment with quizartinib 60 mg/day.

  • Submitted January 5, 2018.
  • Accepted May 26, 2018.