Dr Olivia on the Phase 3 QuANTUM-Wild Trial of Quizartinib in Newly Diagnosed FLT3-ITD–Negative AML

“We’re very excited because this is a promising trial that may promote prolongation of overall survival [OS] in patients with FLT3-ITD–negative [disease]. Even though they have better survival than patients with FLT3-ITD[–positive disease], [patients with] FLT3 wild-type [disease] still have a poor [prognosis in terms of] OS which needs improvement.”

Esther Natalie Oliva, MD, a senior consultant hematologist at London North West Healthcare NHS Trust, discusses the rationale for the phase 3 QuANTUM-Wild trial (NCT06578247) of quizartinib (Vanflyta) plus chemotherapy in newly diagnosed patients with FLT3-ITD–negative acute myeloid leukemia (AML).

Data from the phase 2 QUIWI trial (NCT04107727) demonstrated that patients who received quizartinib in combination with 7+3 chemotherapy experienced an overall survival benefit compared with those who received placebo with 7+3 chemotherapy, Olivia says. Patients who received quizartinib experienced a 37% reduction in the risk of death compared with those in the placebo arm (HR, 0.63; 95% CI, 0.44-0.91; 2-sided P = .0121). These data established the background and rationale for QuANTUM-Wild, she continues. QuANTUM-Wild is planned to be conducted across approximately 260 sites worldwide.

QuANTUM-Wild is an ongoing study that is comparing quizartinib plus chemotherapy with placebo plus chemotherapy in newly diagnosed patients with FLT3-ITD–negative AML. Eligible patients will be randomly assigned 2:2:1 to receive 7+3 chemotherapy and quizartinib during induction and consolidation followed by quizartinib maintenance; 7+3 chemotherapy and placebo during induction and consolidation followed by placebo maintenance; or 7+3 chemotherapy and quizartinib during induction and consolidation followed by placebo during maintenance, Olivia explains.

Overall survival represents the primary end point of the study. Secondary end points include event-free survival, duration of complete response (CR), relapse-free survival, CR rate, CR with minimal or measurable residual disease negativity, and safety, Olivia adds. Key exploratory end points include composite CR rate, patient-reported outcomes, and biomarker assessments.

Key enrollment criteria include being between the ages of 18 to 70 years and having an ECOG performance status of 0 to 2. The only prior treatments for AML that are permitted are leukapheresis, hydroxyurea for the treatment of hyperleukocytosis, cranial radiotherapy for central nervous system leukostasis, prophylactic intrathecal chemotherapy, and growth factor/cytokine support.

In December 2024, Daiichi Sankyo announced that the first patient had been dosed in QuANTUM-Wild. The estimated target enrollment is 700 patients, and the estimated primary completion of the study is June 2030.