FLT3mut+ Relapsed/Refractory AML Treatment Submits New Drug Application

Recently, Astellas Pharma Inc announced its new drug application (NDA) to the US Food and Drug administration (FDA) for gilteritinib (ASP2215) for the treatment of FLT3 mutation-positive (FLT3mut+) relapsed or refractory acute myeloid leukemia (AML).

Gilteritinib is a novel, small molecule inhibitor of the tyrosine kinases FLT3/AXL. The drug is currently in Phase 3 development, and preclinical studies have exhibited its superior antitumor effects when administered with chemotherapy treatment of cytarabine (AraC) and either daunorubicin (DNR) or idarubicin (IDR) compared with combination chemotherapy.¹

AML is a rare cancer that affects the blood and bone marrow in which excess, immature white blood cells accumulate.

The Phase 3 ADMIRAL trial is an open-label, multicenter, randomized study of gilteritinib versus salvage chemotherapy in adult patients with FLT3 mutations who are refractory to or have relapsed after first-line AML therapy. The overall survival and CR (complete remission) / CRh (CR with partial hematological recovery) rate are the co-primary endpoints of the ongoing trial.²

The current primary outcomes measures include the relapse-free survival (RFS), which will be measured from the time of randomization up to 61 months or until documented relapse or death from any cause occurs. Relapse after CR will be defined as bone marrow blasts of 5% or greater, any circulating blasts, and/or any extra-medullary blast foci as per Revised International Working Group (IWG) criteria. An independent review committee will determine relapse events and conduct efficacy assessments unless specifically stated otherwise.³

Three hundred and seventy-one participants with FLT3 mutations present in their bone marrow or whole blood, as determined by central lab, are currently enrolled in the study. Participants have been randomized in a 2:1 ratio to be administered oral gilteritinib (120 mg) or salvage chemotherapy. The current estimated primary completion date for the study is March 2024.

Following the submission in Japan, on March 29, 2018, Astellas submitted a NDA for approval of gilteritinib in the same patient population to the FDA. Data from the ongoing pivotal Phase 3 ADMIRAL study, which is evaluating gilteritinib in adult patients with FLT3mut+ relapsed or refractory AML, is serving as the basis for the applications for marketing approval of gilteritinib.

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References:

1. Gilteritinib (ASP2215), a Novel FLT3/AXL Inhibitor: Preclinical Evaluation in Combination with Azacitidine in Acute Myeloid Leukemia. bloodjournal.org/content/128/22/2830?sso-checked=true. Accessed April 25, 2018.
2. Astellas Submits New Drug Applications for Approval of Gilteritinib for the Treatment of FLT3mut+ Relapsed or Refractory Acute Myeloid Leukemia. newsroom.astellas.us/2018-04-23-Astellas-Submits-New-Drug-Applications-for-Approval-of-Gilteritinib-for-the-Treatment-of-FLT3mut-Relapsed-or-Refractory-Acute-Myeloid-Leukemia. Accessed April 25, 2018.
3. A Study of ASP2215 (Gilteritinib), Administered as Maintenance Therapy Following Induction/Consolidation Therapy for Subjects With FMS-like Tyrosine Kinase 3 (FLT3/ITD) Acute Myeloid Leukemia (AML) in First Complete Remission. clinicaltrials.gov/ct2/show/record/NCT02927262?term=gilteritinib&cond=AML&rank=1. Accessed April 25, 2018.