The initial patient has commenced treatment in the QuANTUM-Wild phase 3 study, investigating the use of Daiichi Sankyo’s Vanflyta (quizartinib) alongside standard intensive induction and consolidation chemotherapy. This is followed by single-agent maintenance in adults diagnosed with FLT3-ITD negative acute myeloid leukemia (AML).
AML is known as a particularly aggressive form of blood cancer, boasting a five-year survival rate of roughly 32%. Patients harboring FLT3 gene mutations, like FLT3-ITD, have shown improved outcomes with targeted FLT3 inhibitor therapies. However, about 90% of AML patients exhibit overexpression of FLT3, irrespective of mutation status. Currently, FLT3 inhibitors are lacking approval for patients devoid of FLT3 mutations.
“Early findings have demonstrated promising results with Vanflyta in patients who have FLT3-ITD negative acute myeloid leukemia, encompassing those without FLT3 mutations and those with TKD mutations,” remarked Mark Rutstein, MD, global head of oncology clinical development at Daiichi Sankyo. “We initiated the QuANTUM-Wild trial to further investigate Vanflyta’s role combined with conventional chemotherapy and as maintenance monotherapy, targeting AML patients in need of novel treatment strategies to potentially lower relapse risk and enhance survival.”
The QuANTUM-Wild study kicked off subsequent to insights from the QUIWI phase 2 study assessing Vanflyta with standard chemotherapy and as monotherapy in adults newly diagnosed with FLT3-ITD negative AML. Final results were showcased at the 2024 American Society of Hematology Annual Meeting.
QuANTUM-Wild is a global, randomized, double-blind, placebo-controlled phase 3 trial exploring Vanflyta’s efficacy and safety in coordination with a standard induction and consolidation regimen, including allogeneic hematopoietic stem cell transplant (HSCT), followed by maintenance monotherapy for adults aged 18 to 70 with newly diagnosed FLT3-ITD negative AML.
Participants will be allocated in a 2:2:1 ratio across three treatment groups. In Arms A and B, Vanflyta or a placebo, paired with cytarabine and anthracycline induction and cytarabine consolidation therapy, is administered, succeeded by up to three years of single-agent maintenance.
Primary endpoints for Arms A and B focus on overall survival, while secondary endpoints include event-free survival, response duration, relapse-free survival, complete remission rate (CR), CR with minimal or measurable residual disease negativity, pharmacokinetic evaluations, and safety, including treatment emergent adverse events.
Exploratory arm analysis in the maintenance phase will see Arm C patients receive Vanflyta with intensive chemotherapy, followed by placebo maintenance monotherapy.
About 700 participants will join the QuANTUM-Wild trial spanning Asia, Australia, Europe, North America, and South America.
AML, a prevalent adult leukemia, confronts a five-year survival statistic of around 32%. Worldwide diagnoses numbered about 144,000, with over 130,000 deaths recorded in 2021.
FLT3 inhibitors have improved survival prospects for patients carrying FLT3 mutations, particularly FLT3-ITD. Yet, 90% of AML cases show FLT3 overexpression, absent of activation mutations. Notably, FLT3 inhibitors approved use in patients without mutations remains absent.
FLT3, a receptor tyrosine kinase, crucial for blood cell development, may, if continually activated, foster AML progression and expansion.
Vanflyta, a selective oral FLT3 inhibitor, secures approval in over 30 nations in combination with standard cytarabine and anthracycline therapies, and as maintenance monotherapy post-consolidation for freshly diagnosed AML patients with FLT3-ITD positivity, based on QuANTUM-First results. However, U.S. guidelines do not recognize Vanflyta as monotherapy post-allogeneic HSCT, with improved survival evidence lacking in this context.
In Japan, Vanflyta also garners approval for relapsed/refractory AML patients with FLT3-ITD positive status, verified via approved testing, based on QuANTUM-R findings.
The Vanflyta clinical program encompasses the QuANTUM-Wild phase 3 trial for adults with newly diagnosed FLT3-ITD negative AML, a phase 1/2 study in children and adolescents with relapsed/refractory FLT3-ITD positive AML in Europe, Asia, and North America, alongside multiple phase 1/2 combination trials through strategic ties with The University of Texas MD Anderson Cancer Center.
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