QUANTUM-WILD: A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF QUIZARTINIB IN COMBINATION WITH CHEMOTHERAPY AND AS SINGLE-AGENT MAINTENANCE IN FLT3-ITD–NEGATIVE ACUTE MYELOID LEUKEMIA

Quizartinib (Quiz) is an oral, selective, type-II FMS-related tyrosine kinase 3 (FLT3) inhibitor with potent activity against wild-type FLT3, FLT3-internal tandem duplications (ITDs), and other kinase domain variants. Quiz is approved for patients with FLT3-ITD-positive newly diagnosed (ND) acute myeloid leukemia (AML) based on the QuANTUM-First trial (ClinicalTrials.gov: NCT02668653) results. FLT3 gene mutations are observed in ∼ 30% of AML cases, most commonly as ITDs, but they are not the only mechanism affecting FLT3 activation. Elevated FLT3 receptor expression is observed in nearly all AML cases, and high levels of FLT3 gene expression are detected in 70–100% of AML blasts, independent of the presence of FLT3 mutations, potentially contributing to leukemic cell survival and proliferation. Evidence from preclinical and clinical studies supports Quiz activity in FLT3-ITD-negative AML. In the randomized, placebo-controlled, phase 2 QUIWI trial, the addition of Quiz to Induction and Consolidation chemotherapy, followed by up to 12 months of single-agent quiz Maintenance for patients achieving complete remission (CR) or CR with incomplete count recovery (CRi), significantly prolonged overall survival (OS) versus placebo in patients with ND FLT3-ITD-negative AML. QuANTUM-Wild is an ongoing, global, phase 3, double-blind, placebo-controlled trial evaluating Quiz with standard induction/consolidation chemotherapy and as maintenance monotherapy in patients with ND FLT3-ITD-negative AML (ClinicalTrials.gov: NCT06578247). Eligible patients are aged 18–70 years with ND FLT3-ITD-negative AML defined as FLT3-ITD allelic frequency < 5%. Treatment includes standard induction with cytarabine and an anthracycline plus Quiz/placebo for 14 days (up to 2 cycles), followed by up to 4 cycles of consolidation with high-dose cytarabine and Quiz/placebo for 14 days (+/– allogeneic hematopoietic stem cell transplantation at investigator discretion), and then single-agent maintenance with Quiz/placebo in 28-day cycles for up to 36 cycles. Patients are randomized 2:2:1 into 3 arms: Arm A (Quiz in all phases), Arm B (placebo in all phases), or Arm C (Quiz in induction/consolidation and placebo in maintenance). Quiz is administered at 60 mg once daily and reduced to 30 mg if combined with strong CYP3A inhibitors. The primary endpoint is OS between Arms A and B. Secondary endpoints include OS between Arm C and Arm B (descriptive), event-free survival, relapse-free survival, complete remission rate and duration, measurable residual disease (by FLT3-ITD in all patients and by NPM1/CBF if present), and safety between Arm A vs Arm B. Planned enrollment is ∼700 patients, with 280 each in Arms A and B, and 140 in Arm C. Enrollment is currently ongoing and approximately 260 sites are planned across North and South America, Europe, Asia, and Australia. This study is sponsored by Daiichi Sankyo Co., Ltd. © American Society of Hematology (2024). Reused with permission.