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    BIOMARKER:

    FLT3 D835

    i
    Other names: FLT3, Fms Related Tyrosine Kinase 3, Receptor-Type Tyrosine-Protein Kinase FLT3, Stem Cell Tyrosine Kinase 1, Fms-Like Tyrosine Kinase 3, CD135, FLK-2, STK1, Growth Factor Receptor Tyrosine Kinase Type III, Fetal Liver Kinase 2
    Entrez ID:
    2322
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    Related tests:
    11ms
    NCI-2021-06095: ASTX727, Venetoclax, and Gilteritinib for the Treatment of Newly Diagnosed, Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome (clinicaltrials.gov)
    P1/2, N=42, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2025 --> Jan 2026
    Trial completion date • Trial primary completion date
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation • FLT3 mutation • FLT3 D835
    |
    Venclexta (venetoclax) • Xospata (gilteritinib) • Inqovi (decitabine/cedazuridine)
    11ms
    LACEWING: A Study of ASP2215 (Gilteritinib) by Itself, ASP2215 Combined With Azacitidine or Azacitidine by Itself to Treat Adult Patients Who Have Recently Been Diagnosed With Acute Myeloid Leukemia With a FLT3 Gene Mutation and Who Cannot Receive Standard Chemotherapy (clinicaltrials.gov)
    P3, N=183, Completed, Astellas Pharma Global Development, Inc. | Active, not recruiting --> Completed
    Trial completion
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3 mutation • FLT3 D835 • FLT3 I836
    |
    Xospata (gilteritinib) • azacitidine
    12ms
    Discovery of 3-amide-pyrimidine-based derivatives as potential fms-like tyrosine receptor kinase 3 (FLT3) inhibitors for treating acute myelogenous leukemia. (PubMed, Bioorg Med Chem Lett)
    To discover next-generation FLT3 inhibitors and gather additional structure-activity relationship (SAR) information, we performed structural modifications of G-749 (denfivontinib) utilizing structure simplification and scaffold hopping strategies...Furthermore, it significantly reduced reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP), and strongly inhibited FLT3-mediated signaling pathways. These findings, along with the obtained SAR information, provide valuable insights for the further development of FLT3 inhibitors.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation • FLT3 D835Y • FLT3 D835
    |
    denfivontinib (SKI-G-801)
    1year
    Target-Capture Next-Generation Sequencing (NGS) for Use in Molecular-Based Research of Myeloid Measurable Residual Disease (MRD) (AMP 2024)
    Target-capture NGS provides the opportunity to evaluate many genes in a single assay. Suitability for MRD requires highly uniform and sensitive target enrichment. Our study demonstrated reliable and accurate detection of variants down to 0.05% VAF, providing researchers with the capability to use capture-based NGS for myeloid MRD monitoring.
    Next-generation sequencing
    |
    FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • JAK2 (Janus kinase 2)
    |
    FLT3-ITD mutation • NPM1 mutation • FLT3 D835Y • FLT3 D835 • IDH2 R172K • KIT D816V • IDH1 R132C • JAK2 V617F • IDH1 R132 • IDH2 R172
    |
    SureSeq™ Myeloid MRD Panel
    1year
    ADMIRAL: A Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-like Tyrosine Kinase (FLT3) Mutation (clinicaltrials.gov)
    P3, N=371, Active, not recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: Aug 2024 --> Dec 2024
    Trial completion date
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation • FLT3 mutation • FLT3 D835 • FLT3 I836
    |
    cytarabine • Xospata (gilteritinib) • azacitidine • etoposide IV • idarubicin hydrochloride • mitoxantrone • fludarabine IV
    over1year
    Structure-Based Optimization of Pyrazinamide-Containing Macrocyclic Derivatives as Fms-like Tyrosine Kinase 3 (FLT3) Inhibitors to Overcome Clinical Mutations. (PubMed, ACS Pharmacol Transl Sci)
    Furthermore, 8v demonstrated ideal anticancer efficacy in a Ba/F3-FLT3-ITD-D835Y xenograft model. The results suggested that 8v can serve as a promising macrocycle-based FLT3 inhibitor for the treatment of AML.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3 mutation • FLT3 D835Y • FLT3 F691L • FLT3 D835 • FLT3-ITD mutation + FLT3 D835Y + FLT3 F691L
    over1year
    NCI-2019-04959: Azacitidine, Venetoclax, and Gilteritinib in Treating Patients With Recurrent/Refractory FLT3-Mutated Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, or High-Risk Myelodysplastic Syndrome/Myeloproliferative Neoplasm (clinicaltrials.gov)
    P1/2, N=55, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=42 --> 55
    Enrollment closed • Enrollment change
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation • FLT3 mutation • FLT3 D835
    |
    Venclexta (venetoclax) • Xospata (gilteritinib)
    almost2years
    FRIDA: Study of Iadademstat and Gilteritinib in Patients With R/R AML With FMS-like Tyrosine Kinase Mutation (FLT3 Mut+) (clinicaltrials.gov)
    P1, N=50, Recruiting, Oryzon Genomics S.A. | Trial primary completion date: Jan 2024 --> Jan 2025
    Trial primary completion date
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3 mutation • FLT3 D835 • FLT3 I836
    |
    Xospata (gilteritinib) • iadademstat (ORY-1001)
    almost2years
    OGILAR: Study Investigating the Efficacy and Safety of the Addition of Oral-azacitidine to Salvage Treatment by Gilteritinib in Subjects ≥18 Years of Age With Relapsed/Refractory FLT3-mutated Acute Myeloid Leukemia (clinicaltrials.gov)
    P2, N=33, Recruiting, French Innovative Leukemia Organisation | Not yet recruiting --> Recruiting
    Enrollment open
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3 mutation • FLT3 D835 • FLT3 I836
    |
    Xospata (gilteritinib) • Onureg (azacitidine oral)
    almost2years
    Crenolanib Maintenance Following Allogeneic Stem Cell Transplantation in FLT3-positive Acute Myeloid Leukemia Patients (clinicaltrials.gov)
    P2, N=30, Completed, Arog Pharmaceuticals, Inc. | Active, not recruiting --> Completed | N=48 --> 30
    Trial completion • Enrollment change
    |
    HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1)
    |
    FLT3 D835
    |
    crenolanib (ARO-002)
    almost2years
    An imidazo[1,2-a]pyridine-pyridine derivative potently inhibits FLT3-ITD and FLT3-ITD secondary mutants, including gilteritinib-resistant FLT3-ITD/F691L. (PubMed, Eur J Med Chem)
    Recently, several FLT3 inhibitors have demonstrated clinical activity and three are currently approved - midostaurin, quizartinib, and gilteritinib. In summary, compound 24 has inhibition potency on FLT3 comparable to gilteritinib, but a more balanced inhibition on FLT3 secondary mutations, especially FLT3-ITD/F691L which is gilteritinib resistant. Compound 24 may serve as a promising lead for the drug development of either primary or relapsed AML with FLT3 secondary mutations.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation • FLT3 mutation • FLT3 D835Y • FLT3 F691L • FLT3 D835
    |
    Xospata (gilteritinib) • midostaurin • Vanflyta (quizartinib)
    2years
    Discovery of benzimidazole-indazole derivatives as potent FLT3-tyrosine kinase domain mutant kinase inhibitors for acute myeloid leukemia. (PubMed, Eur J Med Chem)
    More importantly, 22f showed single-digit nanomolar GI values in the mutant FLT kinase expressed Ba/F3 cell lines including FLT-D835Y (GI = 0.29 nM) and FLT3-F691L (GI = 2.87 nM). Molecular docking studies indicated that the compound exhibits a well-fitted binding mode as a type 1 inhibitor in the homology model of active conformation of FLT3 kinase.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3 mutation • FLT3 D835Y • FLT3 F691L • FLT3 D835