Vanflyta (quizartinib)

P1/2, N=73, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2026 --> Jan 2028 | Trial primary completion date: Jan 2026 --> Jan 2028

Initial treatment with hydroxyurea and leukapheresis followed by azacitidine and venetoclax resulted in an inadequate treatment response. Given the lack of research on the FLT3 V491L mutation, we conducted an ex vivo sensitivity study using the patient's diagnostic bone marrow blasts to assess and compare the anti-leukemic efficacy of midostaurin, quizartinib, and gilteritinib...Treatment of relapsed AML with a non-canonical mutation is challenging due to the lack of data regarding FLT3 inhibitors. This case highlights the potential role of gilteritinib in targeting the rare FLT3 V491L mutation, underscoring the need for further research and improved accessibility to effective therapies.

In FLT3-internal tandem duplication (FLT3-ITD) AML, FLT3 inhibitors such as quizartinib improve outcomes, but resistance limits long-term efficacy...Finally, analysis of IFNγ signaling and resistance in patient-derived AML blasts revealed variable sensitivity, suggesting the presence of additional compensatory mechanisms. These findings reveal IFNγ signaling as a mechanism of resistance, highlighting a potential therapeutic vulnerability in FLT3-mutated AML.

Canertinib exerted similar effects on MV4-11-ACR cells as on the parental cells. Canertinib is an FLT3 inhibitor that directly targets the FLT3 protein to overcome FLT3 mutations and AC220 resistance in acute myeloid leukemia. These findings support canertinib as a promising candidate to overcome acquired resistance to FLT3 inhibitors.

P1/2, N=52, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

P1/2, N=80, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

In this review, we summarize the human myeloid leukemia cell lines that express mutated FLT3 and the effect of several drugs on these cell lines. Our aim in this review is to provide clinicians with a basic science understanding of human myeloid leukemia cell lines and to provide scientific researchers with the clinical implications of FLT3 signaling inhibition.

Here, we applied our recently developed single-cell lineage tracing method ReSisTrace to identify cells that are intrinsically resistant or sensitive to the FLT3 inhibitors midostaurin and quizartinib in AML with FLT3-ITD mutations...In addition, in an FLT3-ITD-positive AML patient-derived xenograft (PDX) mouse model, the CC-90009 and quizartinib combination showed significantly higher anti-tumor efficacy and prolonged overall survival compared to either treatment alone...Vistusertib (mTOR inhibitor), linsitinib (IGF1R and insulin receptor inhibitor), and meisoindigo (IGF1R and Src family kinase inhibitor), all inhibiting pathways parallel to or downstream of oncogenic FLT3 signaling, were predicted and validated to sensitize FLT3-mutated cell lines and primary cells to FLT3 inhibitors. Collectively, these findings demonstrate the ability of ReSisTrace to unveil pre-existing transcriptional features of treatment vulnerability in hematological cancers and elucidate strategies for enhancing FLT3 inhibitor treatment efficacy in FLT3-ITD-mutated AML.

Not available.

The subsequent generation of potent and selective inhibitors has transformed outcomes, culminating in FDA approvals of midostaurin, quizartinib, and gilteritinib. These pathways sustain measurable residual disease (MRD), the key predictor of relapse. Rational combination strategies and MRD-directed approaches are therefore essential to fully realize the curative potential of FLT3 inhibition.

Some therapies have already been developed for actionable mutations: quizartinib for FLT3-ITD mutations is available for newly diagnosed AML, and ivosidenib for IDH1 mutations is awaiting approval...Decisions on allogeneic transplantation and accessibility of investigational drugs are also expected. Detailed diagnosis and prognosis prediction based on the profile of genetic abnormalities should enable precision medicine.

Approved FLT3 inhibitor quizartinib strongly inhibits both FLT3 and c-KIT, resulting in significant myelosuppression...Mechanistic studies in MV4-11 cells revealed downregulated FLT3 signaling after 2 h of treatment with HSB401 and cell cycle arrest and apoptosis in the prolonged experiment. In addition, oral administration of HSB401 significantly suppressed tumor growth in the MV4-11 xenograft mouse model.