FDA panel not ready to recommend quizartinib approval for FLT3-ITD+ AML


– Daiichi Sankyo failed to make the case for approval of its investigational tyrosine kinase inhibitor quizartinib for patients with acute myeloid leukemia bearing the FLT3 internal tandem duplication (ITD) mutation.

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Members of the Oncologic Drugs Advisory Committee (ODAC) of the Food and Drug Administration voted 8-3 not to recommend approval of the drug at this time, despite the prevailing sentiment among oncologists on the panel that, as one stated, “I need this drug. I want this drug.”

The prevailing majority of committee members agreed that the drug may have a place in the treatment of patients with FLT3-mutated AML, but that more robust data were needed to prove it.

Currently, only one agent, gilteritinib (Xospata) is approved by the FDA for the treatment of patients with relapsed or refractory FLT3-mutated AML.


Daiichi Sankyo sought approval for quizartinib based on results of the phase 3 randomized QuANTUM-R trial. In this trial, single-agent therapy with quizartinib slightly but significantly prolonged survival – compared with salvage chemotherapy – of patients with relapsed/refractory FLT3-ITD positive AML.

Median overall survival (OS), the trial’s primary endpoint, was 6.2 months for 245 patients randomized to quizartinib, compared with 4.7 months for 122 patients assigned to salvage chemotherapy, a difference that translated into a hazard ratio (HR) for death of 0.76 (P = .0177).

The patients were randomly assigned on a 2:1 basis to receive either quizartinib or salvage chemotherapy. Quizartinib was dosed 30 mg per day for 15 days, which could be titrated upward to 60 mg daily if the corrected QT interval by Fredericia (QTcF) was 450 ms or less on day 16.

Chemotherapy was the investigator’s choice of one of three specified regimens: either 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). Up to 2 cycles of MEC or FLAG-IDA were permitted; quizartinib and LoDAC were given until lack of benefit, unacceptable toxicity, or until the patient went on to hematopoietic stem cell transplant (HSCT).

Principal investigator Jorge Cortes, MD, from the University of Texas MD Anderson Cancer Center in Houston, speaking in support of the application, said that combined with the phase 2 study results, “these data support a clear and clinically meaningful benefit of quizartinib in this patient population.”

Mark Levis, MD. PhD, from the Johns Hopkins Sidney Kimmel Cancer Center in Baltimore, also spoke in support of the FLT3 inhibitor.

“I have studied both in the lab and in the clinic most FLT3 inhibitors that have been developed, including lestaurtinib, midostaurin, sorafenib and gilteritinib. Quizartinib is the most highly potent and selective FLT3 inhibitor I have ever worked with,” Dr. Levis said.

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