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FDA grants approval to gilteritinib (Xospata®) for the treatment of relapsed or refractory acute myeloid leukemia with FLT3 mutation

Nov 29, 2018

On 28 November 2018, the  US Food and Drug Administration (FDA) granted approval to gilteritinib (Xospata®) for the treatment of adult patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) with a fms like tyrosine kinase 3 ( FLT3) mutation as detected by an FDA-approved test. 1

Gilteritinib is a potent, oral  FLT3/AXL inhibitor, which binds to and inhibits both the wild-type and mutated forms of  FLT3. Data from a phase I/II dose escalation study ( NCT02421939), published in  Lancet Oncology (as  reported by the  AGP) revealed that gilteritinib monotherapy was well tolerated and generated frequent, prolonged, clinically important responses in  FLT3-mutated R/R AML patients.

The approval by the FDA for gilteritinib is based on data from the ongoing phase III randomized ADMIRAL study ( NCT02421939), which is assessing oral gilteritinib 120 mg/day  versus salvage chemotherapy in adult patients with  FLT3 mutations who are refractory to or have relapsed after first-line AML therapy. The primary endpoints of the study are overall survival (OS) and complete remission/complete remission with partial hematologic recovery (CR/CRh) rates. 4 The design and plan of the phase III ADMIRAL study are discussed by  Alexander E. Perl from  Abramson Comprehensive Cancer CenterUniversity of Pennsylvania,  in an  interview with the AGP.

Interim analysis of the phase III ADMIRAL study demonstrated a rate of CR/CRh of 21%, duration of CR/CRh (DOR) of 4.6 months; and the rate of conversion from transfusion dependence to transfusion independence was 31.1% for any 56-day post-baseline period. For patients who achieved a CR/CRh, the median time to first response was 3.6 months (range, 0.9– 9.6 months). The CR/CRh rate was 29 of 126 in patients with FLT3-ITDor FLT3-ITD/TKDand 0 of 12 in patients with FLT3-TKD only. 1

According to the drug manufacturers, Xospata® is the “first and only FLT3 inhibitor approved by the FDA for patients with relapsed or refractory AML with a FLT3mutation.”

  1. PR Newswire: XOSPATA® (gilteritinib) Approved by U.S. FDA for Adult Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML) with a FLT3 Mutation. 2018 Nov 28. [Accessed 2018 Nov 28].
  2. Perl A.E.  et al. Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1–2 study.  Lancet Oncol.2017 Jun 20. DOI:  10.1016/S1470-2045(17)30416-3. [Epub ahead of print].
  3. Perl A.E. et al. An open-label, randomized phase III study of gilteritinib versus salvage chemotherapy in relapsed or refractory FLT3 mutation-positive acute myeloid leukemia. J Clin Oncol. 35, 2017 (suppl; abstr #TPS7067). 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, 2017 June 2–6; Chicago, IL, USA.