Planned analyses of phase 3 trial of gilteritinib as a maintenance therapy after allogeneic hematopoietic stem cell transplantation in patients with Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutations in acute myeloid leukemia (AML).
Astellas Pharma Inc, planned analyses were presented regarding the trial in progress, phase 3 trial of gilteritinib as a maintenance therapy after allogeneic hematopoietic stem cell transplantation in patients with Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutations in acute myeloid leukemia (AML) at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.
AML is a blood and bone marrow cancer characterized by an excess of immature white blood cells. Gilteritinib is a highly selective, potent FLT3/AXL inhibitor.
To date, the phase 3, randomized, double-blind, placebo-controlled multicenter trial includes 149 sites worldwide and 532 adult participants (aged ≥18 years) with FLT3-ITD+ AML in CR1 who are ≥30 days and ≤90 days from scheduled allogeneic HSCT.
“Patients with AML have been found to have a series of different mutations that are important for driving of the disease,” Steven E. Benner, MD, MHS, Senior Vice President and Therapeutic Area Head for Oncology at Astellas Pharma US, Inc told Rare Disease Report ® in a recent interview. “One of the most common is the FLT3 mutation, which occurs in about 30% of patients. When it occurs, it means that those patients have more aggressive disease. They’re more likely to relapse, and when they relapse, and when they relapse, they relapse very poorly.”
He added that gilteritinib is an oral therapy, which allows investigators to target that specific mutation. Furthermore, it is capable of targeting the most common form, which is an internal tandem duplication of the mutation, as well as a terminal mutation that is often associated with resistance to therapy.
“Our drug targets both of those types of FLT3 mutations. Because it’s a potent inhibitor, it has been able to induce complete remissions, including deep molecular responses in patients who received it as a single agent,” he explained.
Among the study’s 532 participants, 346 who experience successful engraftment without uncontrolled graft-versus-host disease (GVHD) or other serious toxicity will be randomized (1:1; stratified by conditioning regimen intensity, time from HSCT [day 0] to randomization [30 to 60 days vs 61 to 90 days], and presence of minimal residual disease [MRD] in the pre-transplant bone marrow sample) to be administered oral gilteritinib (120 mg) or matching placebo as maintenance therapy for 2 years.
Relapse-free survival (RFS) is the primary endpoint in the 2 treatment arms; RFS will be evaluated from the time of randomization to the time of death or morphologic leukemia relapse (as defined by Revised IWG criteria). A key secondary endpoint is overall survival. Safety/tolerability, non-relapse mortality, event-free survival, incidences of acute/chronic GVHD, and MRD include other endpoints. Forty-seven patients have been enrolled as of January 30, 2018, and 11 have been randomized.
“Just at the very end of April we were able to announce that we have submitted a filing [New Drug Application] to both the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan and the US Food and Drug Administration (FDA) in March,” added Dr Benner. “We know now as of last week, the filing has been accepted by the FDA, and that it’s going to go under a Priority Review,”
If approved, this would be the first FLT3 inhibitor for the treatment of FLT3-positive AML in the relapsed refractory setting. Gilteritinib was previously granted priority review.