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.
Contributor Notes
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Kamel is currently a visiting senior lecturer at King’s College London, London, United Kingdom. Lameh is currently at Zail Lab, LLC, San Diego, California.
Funding for this study was provided by Daiichi Sankyo.
Connolly Rohrbach, Karnoub, Liu, and Ito are employees of Daiichi Sankyo and have stock/stock options with Daiichi Sankyo. Kamel is a former employee of Daiichi Sankyo and reports grants or contracts from Bexon Clinical Consulting and Stemline Therapeutics and consulting fees from Stemline Therapeutics. Chang and Khambata-Ford are former employees of Daiichi Sankyo; Chang owns stock/stock options with Daiichi Sankyo. Rivera is an employee of Navigate BioPharma Services, a Novartis subsidiary, and owns stock/stock options with Novartis. Lameh is a former employee of Navigate BioPharma Services and owns stock/stock options with Novartis. Perl reports research grants from AbbVie, Astellas, Daiichi Sankyo, FujiFilm Pharmaceuticals, Bayer, and Syndax Pharmaceuticals; consulting fees from AbbVie, Astellas, Daiichi Sankyo, Forma Therapeutics, and Foghorn Therapeutics; payment for lectures from Astellas and Daiichi Sankyo; support for attending meetings from Daiichi Sankyo for participation on a steering committee; payment for participation on data safety monitoring committee from the Leukemia & Lymphoma Society (Beat AML Master Clinical Trial) and Foghorn Therapeutics; and honoraria for participation on advisory boards from AbbVie, Actinium Pharmaceuticals, Aptose Biosciences, Astellas, BerGenBio, Bristol Myers Squibb, Curis, Daiichi Sankyo, Genentech, Immunogen, Rigel Pharmaceuticals, and Schrödinger. Levis reports research grants from Astellas and FujiFilm Pharmaceuticals; consulting fees from AbbVie, Amgen, Bristol Myers Squibb, Daiichi Sankyo, Jazz Pharmaceuticals, Menarini, Pfizer, and Takeda; and payment for lectures or speakers bureaus from Astellas. Rudenko, Thornes, Todt, Gerhold, Huang, and Miller are employees of Invivoscribe and own stock/stock options with Invivoscribe.
These data have been presented in a poster presentation at the 65th American Society of Hematology Annual Meeting and Exposition 2023; December 11, 2023; San Diego, California.