Daiichi Sankyo Announces First Patient Enrolled in Phase III QuANTUM-First Trial

Daiichi Sankyo Company, Limited recently announced that the first patient has been enrolled in the global Phase III QuANTUM-First study evaluating the oral FLT3-ITD inhibitor quizartinib in patients with newly diagnosed FLT3-ITD-positive (+) acute myeloid leukemia (AML).

QuANTUM-First is a randomized, double-blind, placebo-controlled study evaluating quizartinib in combination with induction and consolidation chemotherapy and as maintenance monotherapy in patients with newly diagnosed FLT3-ITD+ AML. The primary endpoint of the study is event-free survival. Secondary endpoints include overall survival, complete remission rate, composite complete remission rate, and the percentage of subjects achieving a complete remission with no evidence of minimal residual disease.

Approximately 30% of patients with AML have a genetic mutation called FLT3-ITD, which is associated with more aggressive disease, resulting in increased relapse rate and reduced overall survival compared to those without this mutation. FLT3-ITD mutations are more common than FLT3-TKD mutations, which occur in approximately 10% of AML patients. There is controversy as to whether FLT3-TKD mutations carry as poor a prognosis as FLT3-ITD mutations. Currently, there are no approved targeted treatments for FLT3-ITD+ AML, with little change in the treatment of AML for the past 30 years.

“It is well established that patients with FLT3-ITD mutated AML have an overall worse prognosis compared to those without this specific mutation,” said Harry Erba, MD, PhD, Chair of the QANTUM-First Steering Committee and Professor of Medicine and Director of the Hematologic Malignancy Program at the University of Alabama at Birmingham. “In this study we are evaluating whether adding quizartinib to standard first-line chemotherapy will help delay or prevent relapse, which in turn may impact overall survival in patients with FLT3-ITD+ AML.”

“Given the high unmet need in FLT3-ITD+ AML, we are moving forward with a comprehensive clinical development program investigating the role of quizartinib in multiple lines of treatment, including induction and consolidation chemotherapy, maintenance therapy, and salvage therapy,” said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. “Additionally, we also are looking to combine quizartinib with other investigational agents in our pipeline, such as our MDM2 and BRD4 inhibitors, where science suggests combining different mechanisms of action may help improve outcomes.”

QuANTUM-First is expected to enroll more than 500 patients between 18 and 75 years of age in the Americas, Europe and Asia-Pacific. More information about the study is available at www.ClinicalTrials.gov or www.QuantumFirstStudy.com.

Acute myeloid leukemia is the most common type of acute leukemia accounting for about 33% of all new cases of leukemia. An aggressive blood and bone marrow cancer, AML causes uncontrolled growth and accumulation of malignant white blood cells that fail to function normally and interfere with the production of normal blood cells. The 5-year survival rate of AML is approximately 26%, which is the lowest of all leukemias.

Quizartinib is an investigational oral small molecule that potently and selectively inhibits FLT3-ITD (FMS-like tyrosine kinase-3-internal tandem duplication), which is a growth driver of abnormal cells that contribute to the development of AML. Quizartinib has been granted Orphan Drug Designation by the US FDA and European Medicines Agency (EMA) for the treatment of AML. Quizartinib also has been granted Fast Track Designation by the FDA for the treatment of relapsed/refractory AML. Quizartinib has not been approved by any regulatory authority for uses under investigation.
In addition to QuANTUM-First, a global, randomized, open-label, Phase III study called QuANTUM-R is evaluating quizartinib as monotherapy in patients with FLT3-ITD+ AML who are refractory to or have relapsed after first-line treatment with or without hematopoietic stem cell transplant (HSCT). The primary objective of QuANTUM-R is to determine whether quizartinib prolongs overall survival compared to salvage chemotherapy, and the secondary objective is to determine event-free survival. The trial is expected to enroll approximately 363 patients age 18 or older in North America, Europe, and Asia-Pacific. More information about QuANTUM-R is available at www.QuantumRStudy.com or www.ClinicalTrials.gov.