FDA Grants Breakthrough Therapy Designation to Relapsed/Refractory FLT3-ITD AML Treatment


The FDA has granted a breakthrough therapy designation to Daiichi Sankyo Company, Limited’s investigational FLT3 inhibitor, quizartinib, for the treatment of adult patients with relapsed/refractory FLT3-ITD acute myeloid leukemia (AML).

The US Food and Drug Administration (FDA) has granted a breakthrough therapy designation to Daiichi Sankyo Company, Limited’s investigational FLT3 inhibitor, quizartinib, for the treatment of adult patients with relapsed/refractory tyrosine kinase 3-internal tandem duplication (FLT3-ITD) acute myeloid leukemia (AML).

"There have been limited advances over the past several decades for the treatment of relapsed/refractory FLT3-ITD AML, a very aggressive form of the disease associated with poor prognosis,” said Arnaud Lesegretain, vice president, oncology research and development and head, AML franchise, Daiichi Sankyo, in a recent statement. “Quizartinib is the first FLT3 inhibitor to significantly improve overall survival as an oral, single agent compared to chemotherapy in patients with relapsed/refractory AML with FLT3-ITD, an underlying driver of this subtype of AML.”

The pivotal open-label, randomized, phase 3 QuANTUM-R trial of quizartinib—which was presented during the plenary session at the 23rd Congress of the European Hematology Association in June 2018—served as the basis for the designation.

For the trial, the investigators set out to determine if quizartinib monotherapy would prolong overall survival compared with salvage chemotherapy in 367 adults with FLT3-ITD positive AML refractory to or relapsed after first-line treatment with or without hematopoietic stem cell transplantation (HSCT) consolidation or who have relapsed within 6 months after first-line acute myeloid leukemia (AML) therapy.

The primary outcome measure for the trial was overall survival, as measured in the timeframe of 1 year; event-free survival as measured at the end of the trial (5 years and 2 months) served as the trial’s secondary outcome measure. Participants were randomized into 2 treatment arms; the experimental arm received 20 or 30 mg quizartinib tablets, while the active comparator arm received salvage chemotherapy, which consisted of low dose cytarabine (LoDAC); mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC); or fludarabine, cytarabine, and granulocyte colony stimulating factor (G-CSF) with idarubicin (FLAG-IDA).

Quizartinib was found to result in a prolonged overall survival compared with salvage chemotherapy in this patient population. In addition, the safety profile of the FLT3 inhibitor was noted to be consistent with that observed at similar doses in the quizartinib clinical development program. Investigators also noted that the incidence of treatment-emergent adverse events was comparable between patients who received the single agent (n=241) and those who received salvage chemotherapy (n=94). Nausea, thrombocytopenia, fatigue, musculoskeletal pain, pyrexia, anemia, neutropenia, febrile neutropenia, vomiting, and hypokalemia were reported as the most common adverse events (>30%, any Grade) experienced by patients treated with quizartinib.

“We are excited that quizartinib has received Breakthrough Therapy designation and we look forward to working closely with the FDA to bring this potential new treatment option to patients as quickly as possible," Lesegretain added.

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