Quizartinib Prolongs Survival in Some Patients with Relapsed or Refractory AML, Phase 3 Study Shows

Quizartinib Prolongs Survival in Some Patients with Relapsed or Refractory AML, Phase 3 Study Shows

Quizartinib, an inhibitor of the FLT3 molecule, significantly prolongs overall survival compared to salvage chemotherapy in patients with relapsed or refractory acute myeloid leukemia (AML) carrying FLT3-ITD mutations, and who do not respond to or relapse after first-line AML chemotherapy, Daiichi Sankyo announced.

Currently, there are no approved therapies for patients with relapsed or refractory AML with internal tandem duplication (ITD) mutations in the FLT3 gene. This form of the disease is very aggressive and has poor prognosis, including an increased incidence of relapse and increased risk of death when the cancer returns.

“Single agent quizartinib is the first FLT3 inhibitor to show a significant improvement in overall survival compared to cytotoxic chemotherapy in a randomized Phase 3 study of patients with relapsed/refractory AML with FLT3-ITD mutations, a very aggressive form of the disease with limited treatment options,” Antoine Yver, MD, said in a press release. Yver is Daiichi Sankyo’s executive vice president and global head of oncology research and development. 

Quizartinib is Daiichi Sankyo’s lead investigational compound for the treatment of AML. It is an oral selective inhibitor of class III receptor tyrosine kinases, including FMS-related tyrosine kinase 3 (FLT3), which transmit signals from the cell surface into the cell. The signaling pathways stimulated by the FLT3 protein control many important cellular processes, such as the growth and survival of cells, particularly of immature blood cells called hematopoietic progenitor cells.

Mutations in FLT3 are a common cause of AML. These mutations result in abnormal changes in the FLT3 protein that make its signaling pathway turned on permanently. Constant signaling leads to uncontrolled proliferation of abnormal, immature white blood cells, a hallmark of AML.

Therefore, quizartinib, by inhibiting FLT3, prevents the proliferation of mutated leukemic cells and tiggers their death.

The compound is currently in being studied in two Phase 3 trials, the QuANTUM-R for relapsed or refractory AML patients who carry FLT3-ITD mutations (NCT02039726), and the QuANTUM-First for newly diagnosed patients with those mutations (NCT02668653).

QuANTUM-R is a global, randomized study that enrolled 367 patients with FLT3-ITD-mutated AML who did not respond or relapsed within six months of standard first-line therapy, with or without stem cell transplant.

Patients were assigned randomly to receive orally 20 or 30 milligrams of quizartinib, or salvage chemotherapy.

The primary goal of the study was to determine whether quizartinib alone prolonged overall survival compared to salvage chemotherapy, which it did.

Regarding safety, Daiichi Sankyo says it appears consistent with that observed at similar doses tested in other quizartinib studies.

In light of the topline results, Daiichi Sankyo intends to initiate regulatory submissions worldwide for quizartinib. 

“We sincerely thank all of the investigators and patients who participated in this study and will share the results of the QuANTUM-R study at an upcoming medical meeting. We look forward to working with regulatory authorities worldwide to potentially bring quizartinib to patients as quickly as possible,” said Yver.

Quizartinib has been granted fast track and orphan drug designations by the U.S. Food and Drug Administration for the treatment of relapsed or refractory AML.

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