FDA grants gilteritinib priority review for the treatment of R/R AML with FLT3 mutation

On 29 May 2018, the U.S. Food and Drug Administration (FDA) accepted the New Drug Application (NDA) and granted priority review to gilteritinib 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 was granted a Fast Track Designation by the FDA in October 2017.

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.

Furthermore, data from an ongoing phase I dose-escalation study  (NCT02236013), presented at the 59th American Society of Hematology (ASH) Annual Meeting by Keith Pratz, MD, from John Hopkins University, demonstrated that gilteritinib in combination with intensive chemotherapy was “well tolerated” with a maximum tolerated dose at ≥ 120 mg/day in patients with newly diagnosed AML. A higher response to this combination regimen was seen in FLT3-mut+ AML patients.3 In an interview with the AGP, Keith Pratz highlighted that the responses observed in patients treated in this phase I dose escalation trial has been “good so far”.

The NDA approval by the FDA is based on 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 ADMRIAL study are discussed by Alexander E. Perl from Abramson Comprehensive Cancer CenterUniversity of Pennsylvania,  in an interview with the AGP.

  1. PR Newswire: U.S. FDA Grants Priority Review to Astellas' New Drug Application for Gilteritinib for the Treatment of Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML). 2018 May 29. https://www.prnewswire.com/news-releases/us-fda-grants-priority-review-to-astellas-new-drug-application-for-gilteritinib-for-the-treatment-of-adult-patients-with-relapsed-or-refractory-acute-myeloid-leukemia-aml-300655518.html [Accessed 2018 May 29].
  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. Pratz K. et al. Preliminary Results from a Phase 1 Study of Gilteritinib in Combination with Induction and Consolidation Chemotherapy in Subjects with Newly Diagnosed Acute Myeloid Leukemia (AML). Oral Abstract #722: 59th ASH Annual Meeting and Exposition, Atlanta, GA.
  4. 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.
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