On June 16, 2018 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that positive results from the pivotal QuANTUM-R phase 3 study of single agent quizartinib were presented today as a late-breaking oral presentation in the plenary program at the 23rd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Stockholm, Sweden (Press release, Daiichi Sankyo, JUN 16, 2018, View Source [SID1234527368]).

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QuANTUM-R study results showed that patients with relapsed/refractory acute myeloid leukemia (AML) with FLT3-ITD mutations who received single agent quizartinib had a 24 percent reduction in the risk of death compared to patients who received salvage chemotherapy (hazard ratio [HR] = 0.76, P=0.0177, 95 percent CI 0.58-0.98). The median overall survival was 6.2 months (two-sided 95 percent CI 5.3-7.2) for patients treated with quizartinib and 4.7 months (two-sided 95 percent CI 4.0-5.5) for patients treated with salvage chemotherapy. The estimated survival probability at 1 year was 27 percent for patients who received quizartinib and 20 percent for patients who received salvage chemotherapy.

"FLT3-ITD mutated AML represents a high unmet need entity as patients with this aggressive form of the disease have an overall dismal prognosis as evidenced by low response rates to current available therapies, high risk of relapse and a shorter overall survival than those without this mutation," said Jorge E. Cortes, MD, Deputy Chair of the Department of Leukemia in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. "In relapsed/refractory AML with FLT3-ITD mutations, these findings represent the first reported clinical data demonstrating that a single agent can significantly improve overall survival, suggesting that quizartinib could potentially help these patients live longer. Additionally, in the study, a higher proportion of patients received a stem cell transplant in the quizartinib arm compared to the chemotherapy arm."

Secondary and key exploratory analyses including composite complete remission (CRc) are consistent and supportive of the primary analysis.

"Results of this study are consistent with previous phase 2 studies of quizartinib and demonstrate the value of targeting the FLT3-ITD driver mutation. We are encouraged by these data, which will form the basis of regulatory submissions to health authorities. If approved, quizartinib has the potential to redefine the treatment of patients with relapsed/refractory AML with FLT3-ITD mutations," said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. "These results also build on our understanding of this difficult-to-treat type of AML as we continue to explore the potential role of quizartinib in combination with chemotherapy and other novel mechanisms to further advance the treatment of patients with relapsed/refractory and newly-diagnosed AML with FLT3-ITD mutations."

The safety profile observed in QuANTUM-R appears consistent with that observed at similar doses in the quizartinib clinical development program. The median treatment duration with quizartinib was 4 cycles of 28 days (97 days; range: 1-1,182 days) versus 1 cycle (range: 1-2) in the salvage chemotherapy arm. The median relative dose intensity for quizartinib was 89 percent. Incidence of treatment-emergent adverse events were comparable between patients who received single agent quizartinib (n=241) and those who received salvage chemotherapy (n=94). The most common adverse events (>30 percent, any Grade) in patients treated with quizartinib versus chemotherapy, respectively, included nausea (48 vs 42 percent), thrombocytopenia (39 vs 34 percent), fatigue (39 vs 29 percent), musculoskeletal pain (37 vs 28 percent), pyrexia (38 vs 45 percent), anemia (37 vs 32 percent), neutropenia (34 vs 26 percent), febrile neutropenia (34 vs 28 percent), vomiting (33 vs 21 percent) and hypokalemia (32 vs 28 percent). The most common adverse events Grade ≥3 (>10 percent of patients) were thrombocytopenia (35 vs 34 percent), anemia (30 vs 29 percent), neutropenia (32 vs 25 percent), febrile neutropenia (31 vs 21 percent), leukopenia (17 vs 16 percent), sepsis/septic shock (16 vs 18 percent), hypokalemia (12 vs 9 percent) and pneumonia (12 vs 9 percent). QTcF >500 msec occurred in 8 patients (3.3 percent) and 2 out of 241 patients discontinued quizartinib due to QTcF prolongation. There were no reported events of Grade 4 QTcF prolongation (Torsade de Pointe, sudden death or cardiac arrest) in the quizartinib arm.

About the QuANTUM-R Study

QuANTUM-R is a pivotal, global, phase 3, open-label randomized study that enrolled 367 patients with FLT3-ITD-mutated AML who were refractory to or in relapse following (with duration of remission of six months or less) standard first-line AML therapy with or without hematopoietic stem cell transplantation (HSCT). Patients were randomized in a 2:1 ratio to receive either single agent oral quizartinib (60 mg, with 30 mg lead-in) or salvage chemotherapy. The primary objective of the study was to determine whether single agent quizartinib prolonged overall survival compared to salvage chemotherapy.

About Quizartinib

Quizartinib, the lead investigational agent in the AML Franchise of the Daiichi Sankyo Cancer Enterprise, is an oral selective FLT3 inhibitor currently in global phase 3 development for relapsed/refractory (QuANTUM-R) and newly-diagnosed (QuANTUM-First) AML with FLT3-ITD mutations, and phase 2 development for relapsed/refractory AML with FLT3-ITD mutations in Japan.

Quizartinib has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of relapsed/refractory AML. Quizartinib also has been granted Orphan Drug designation by the FDA and European Medicines Agency (EMA) for the treatment of AML. Quizartinib is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

About Acute Myeloid Leukemia with FLT3-ITD Mutations

AML is an aggressive blood and bone marrow cancer that causes uncontrolled growth and accumulation of malignant white blood cells that fail to function normally and interfere with the production of normal blood cells.1 The five-year survival rate of AML reported from 2005 to 2011 was approximately 26 percent, which was the lowest of all leukemias.1

FLT3 gene mutations are one of the most common genetic abnormalities in AML.2 The FLT3-ITD mutation is the most common FLT3 mutation, affecting approximately one in four patients with AML.3,4,5,6 Patients with FLT3-ITD-mutated AML have a worse overall prognosis, including an increased incidence of relapse, an increased risk of death following relapseand a higher likelihood of relapse following HSCT as compared to those without this mutation.7,8