QuANTUM-First: Clinical Validation of the LeukoStrat Companion Diagnostic for the Selection of Patients With Acute Myeloid Leukemia Harboring FMS-Like Tyrosine Kinase 3-Internal Tandem Duplications for Treatment With Quizartinib.

Context.—: The phase 3 study Quizartinib With Standard of Care Chemotherapy and as Continuation Therapy in Patients With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia (AML) (QuANTUM-First; NCT02668653) demonstrated improved overall survival (OS) in newly diagnosed patients with FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication-positive AML treated with the FLT3 inhibitor quizartinib over placebo, leading to the approval of quizartinib in this population.

Objective.—: To describe the bridging study between the Navigate clinical trial assay (CTA) used for patient selection in QuANTUM-First and the LeukoStrat CDx [companion diagnostic] FLT3 Mutation Assay, necessary to establish concordance between these 2 assays to support the QuANTUM-First supplemental premarket application for the CDx.

Design.—: Assay agreement was established if lower bounds of the 95% CI for both positive and negative percentage agreement were 90% or greater. Treatment efficacy was evaluated to assess if OS in the intent-to-treat (ITT) CDx+ population (CTA+, CDx+) and the QuANTUM-First ITT were comparable.

Results.—: The lower bounds of the 95% CI were greater than 90% for positive percentage agreement (94.7%) and negative percentage agreement (100%) based on results from 1029 patients, demonstrating agreement between CTA and CDx. The OS benefit provided by quizartinib in the ITT CDx+ population in the bridging study, with a median OS of 29.4 months for quizartinib versus 14.8 months for placebo (hazard ratio, 0.794; 2-sided stratified log-rank P = .06), was comparable with the OS benefit in the QuANTUM-First ITT.

Conclusions.—: The LeukoStrat CDx FLT3 Mutation Assay aids in selecting newly diagnosed patients with FLT3 internal tandem duplication-positive AML for quizartinib therapy.