Daiichi Sankyo has dosed the first patient in the QuANTUM-Wild phase 3 trial, evaluating Vanflyta (quizartinib) in adult patients with newly diagnosed FLT3-ITD negative acute myeloid leukemia (AML). This global study aims to determine the efficacy and safety of Vanflyta when combined with standard intensive induction and consolidation chemotherapy, followed by single-agent maintenance therapy.
The QuANTUM-Wild trial is a randomized, double-blind, placebo-controlled study designed to enroll approximately 700 patients across Asia, Australia, Europe, North America, and South America. Patients aged 18 to 70 with newly diagnosed FLT3-ITD negative AML will be randomized 2:2:1 into three treatment arms. Arms A and B will receive Vanflyta or placebo, respectively, in combination with cytarabine and anthracycline induction and cytarabine consolidation chemotherapy, followed by up to three years of single-agent maintenance therapy. Arm C will receive Vanflyta in combination with intensive induction and consolidation chemotherapy followed by placebo maintenance monotherapy for exploratory analyses.
The primary endpoint for Arms A and B is overall survival. Secondary endpoints include event-free survival, duration of complete response, relapse-free survival, complete remission rate (CR), CR with minimal or measurable residual disease negativity, pharmacokinetic assessments, and safety measures including treatment-emergent adverse events.
Rationale Behind the Trial
The QuANTUM-Wild trial was initiated based on results from the QUIWI phase 2 trial, which evaluated Vanflyta in combination with standard intensive chemotherapy and as subsequent maintenance monotherapy in adult patients with newly diagnosed FLT3-ITD negative AML. The final results of QUIWI were presented at the 2024 American Society of Hematology Annual Meeting.
According to Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo, "Preliminary data have shown promising results for VANFLYTA in patients with FLT3-ITD negative acute myeloid leukemia, which includes patients without FLT3 mutations and patients with TKD mutations. We have initiated the QuANTUM-Wild trial to further confirm the potential role of VANFLYTA combined with standard chemotherapy and as subsequent maintenance monotherapy in this broader population of patients with AML who are in need of new treatment options to potentially reduce the risk of relapse and improve overall survival."
About Acute Myeloid Leukemia (AML)
AML is an aggressive blood cancer with a five-year overall survival rate of approximately 32%. Approximately 144,000 new cases of AML were diagnosed globally, with more than 130,000 deaths reported in 2021. Targeted therapy with FLT3 inhibitors has improved survival for some patients with FLT3 gene mutations, which most commonly occur as FLT3-ITD. However, about 90% of all patients with AML overexpress FLT3 regardless of activating mutations, and no FLT3 inhibitors are currently approved for patients without FLT3 mutations.
About Vanflyta (Quizartinib)
Vanflyta is an oral, highly potent and selective type II FLT3 inhibitor approved in more than 30 countries in combination with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy, and as maintenance monotherapy following consolidation, for the treatment of adult patients with newly diagnosed AML that is FLT3-ITD positive based on the results from the QuANTUM-First trial. In the U.S., Vanflyta is not indicated as maintenance monotherapy following allogeneic HSCT; improvement in overall survival with Vanflyta in this setting has not been demonstrated. Vanflyta is also approved in Japan for the treatment of patients with relapsed/refractory AML that is FLT3-ITD mutation positive, as detected by an approved test, based on results from the QuANTUM-R trial.
Safety Information
Vanflyta carries a boxed warning for QT prolongation, Torsades de Pointes, and cardiac arrest. It is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the VANFLYTA REMS. Contraindications include severe hypokalemia, severe hypomagnesemia, long QT syndrome, or a history of ventricular arrhythmias or torsades de pointes.
