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Gene FLT3
Variant exon 14 ins
Impact List indel
Protein Effect gain of function - predicted
Gene Variant Descriptions FLT3 exon 14 ins refers to a series of internal tandem duplications (ITD) typically occurring in exon 14 and within the juxtamembrane domain of the Flt3 protein (PMID: 12970773). Exon 14 ins mutations often result in constitutive activation of Flt3 (PMID: 12970773) and therefore, is predicted to lead to a gain of Flt3 protein function.
Associated Drug Resistance

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No Variant Reference Transcript is Available.
No transcript is Available.

Filtering

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  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FLT3 exon 14 ins hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited growth of transformed hematologic cells expressing FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). 31309543
FLT3 exon 14 ins acute myeloid leukemia sensitive MRX-2843 Preclinical - Cell line xenograft Actionable In a preclinical study, MRX-2843 inhibited Flt3 activation, resulted in growth inhibition in acute myeloid leukemia cell lines harboring FLT3 internal tandem duplication (ITD) in culture and in cell line xenograft models, and prolonged survival in patient-derived xenograft models (PMID: 27158668). 27158668
FLT3 exon 14 ins Advanced Solid Tumor sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3 internal tandem duplication (ITD) demonstrated sensitivity to Crenolanib treatment in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins acute myeloid leukemia sensitive GSK690693 + Venetoclax Preclinical - Cell culture Actionable In a preclinical study, GSK690693 and Venclexta (venetoclax) combination treatment synergistically induced cell death of acute myeloid leukemia cell lines harboring FLT3 internal tandem duplication (ITD) in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins acute myeloid leukemia sensitive CCT137690 + Palbociclib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Ibrance (palbociclib) and CCT137690 resulted in a synergistic effect in acute myeloid leukemia cells harboring a FLT3-ITD, demonstrating a greater reduced cell viability compared to either agent alone (PMID: 30544932). 30544932
FLT3 exon 14 ins leukemia sensitive FN-1501 Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with FN-1501 reduced phoshorylation of FLT3 and downstream STAT5, ERK, and AKT, induced apoptosis and cell-cycle arrest, and decreased proliferation in a human leukemia cell line harboring a FLT3-ITD mutation in culture, and induced tumor regression in xenograft models (PMID: 29357250). 29357250
FLT3 exon 14 ins acute myeloid leukemia sensitive LT-171-861 Preclinical - Cell line xenograft Actionable In a preclinical study, LT-171-861 inhibited cell growth, decreased FLT3 signaling, and induced apoptosis in acute myeloid leukemia cell lines and primary patient-derived peripheral blood mononuclear cells harboring FLT3-ITD mutations in culture, and resulted in tumor regression and prolonged survival in cell line xenograft models (PMID: 33391463). 33391463
FLT3 exon 14 ins acute myeloid leukemia sensitive LAM-003 + Tazemetostat Preclinical - Cell culture Actionable In a preclinical study, LAM-003 and Tazemetostat (EPZ-6438) combination treatment synergistically inhibited viability of acute myeloid leukemia cell lines harboring FLT3 internal tandem duplication (ITD) in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins myeloid leukemia sensitive A-419259 Preclinical - Cell culture Actionable In a preclinical study, transformed myeloid leukemia cells expressing FLT3-ITD were sensitive to treatment with A-419259, demonstrating inhibition of cell growth in culture (PMID: 31790499). 31790499
FLT3 exon 14 ins acute myeloid leukemia sensitive A-419259 Preclinical - Cell culture Actionable In a preclinical study, A-419259 treatment inhibited viability of an acute myeloid leukemia cell line harboring FLT3-ITD in culture (PMID: 31790499). 31790499
FLT3 exon 14 ins acute myeloid leukemia sensitive Entospletinib Preclinical - Cell culture Actionable In a preclinical study, Entospletinib (GS-9973) treatment inhibited proliferation of acute myeloid leukemia cells harboring FLT3 exon 14 insertion (FLT3-ITD) in culture (PMID: 31992353). 31992353
FLT3 exon 14 ins acute myeloid leukemia sensitive Entospletinib Preclinical - Patient cell culture Actionable In a preclinical study, FLT3-ITD mutations correlated with sensitivity to Entospletinib in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). 30333627
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive KW-2449 Preclinical - Patient cell culture Actionable In a preclinical study, FLT3-ITD mutations correlated with sensitivity to KW-2449 in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). 30333627
FLT3 exon 14 ins acute myeloid leukemia sensitive Gilteritinib Phase Ib/II Actionable In a Phase I/II trial, treatment with Gilteritinib (ASP2215) at a dose of 80mg/day or higher resulted in an overall response rate of 55% (77/141) in patients with relapsed or refractory acute myeloid leukemia harboring FLT3 internal tandem duplication mutations (PMID: 28645776; NCT02014558). 28645776
FLT3 exon 14 ins acute myeloid leukemia sensitive Gilteritinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (ADMIRAL) that supported FDA approval, Xospata (gilteritinib) treatment resulted in complete remission (CR) or CR with partial hematologic recovery in 21% (29/138) of patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD; exon 14 insertion), D835, or I836 mutation (FDA.gov; NCT02421939). detail... detail...
FLT3 exon 14 ins acute myeloid leukemia sensitive Gilteritinib Guideline Actionable Xospata (gilteritinib) is included in the guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org). detail...
FLT3 exon 14 ins leukemia predicted - sensitive GMI-1359 Preclinical - Cell line xenograft Actionable In a preclinical study, GMI-1359 in combination with chemotherapy resulted in significant survival benefit compared to chemotherapy alone (67% vs 30%) in cell line xenograft models of FLT3-ITD leukemia (Blood 2015 126(23):3790). detail...
FLT3 exon 14 ins acute myeloid leukemia sensitive FLT3/CD3 Fabsc antibody Preclinical - Cell culture Actionable In a preclinical study, treatment of an acute myeloid leukemia (AML) cell lines or patient-derived xenograft (PDX)-derived AML cells harboring a heterozygous FLT3-ITD mutation with a Fabsc FLT3/CD3 bi-specific antibody resulted in near complete eradication of AML cells in culture (PMID: 28895560). 28895560
FLT3 exon 14 ins acute myeloid leukemia sensitive Abivertinib Preclinical - Patient cell culture Actionable In a preclinical study, Abivertinib (AC0010) treatment inhibited PI3K signaling and phosphorylation of Btk, Flt3, and Stat5, induced apoptosis and cell cycle arrest, reduced viability, and inhibited colony formation in acute myeloid leukemia cell lines harboring FLT3 exon 14 insertion, and decreased viability of patient-derived acute myeloid leukemia blasts harboring FLT3 exon 14 insertion in culture (PMID: 31310800). 31310800
FLT3 exon 14 ins B-cell acute lymphoblastic leukemia predicted - sensitive CD19/CD22 CAR T cells Case Reports/Case Series Actionable In a clinical case study, CD19/CD22 CAR T cell treatment resulted in rapid and durable suppression of leukemia cells in a patient with refractory acute B-cell lymphoblastic leukemia harboring a FLT3 internal tandem duplication (ITD) mutation (PMID: 32005917). 32005917
FLT3 exon 14 ins acute myeloid leukemia sensitive Decitabine + Sorafenib Guideline Actionable Nexavar (sorafenib) in combination with Dacogen (decitabine) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org). detail...
FLT3 exon 14 ins Advanced Solid Tumor predicted - sensitive Cabozantinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing a FLT3-ITD mutation were sensitive to Cometriq (cabozantinib) in culture (PMID: 21926191). 21926191
FLT3 exon 14 ins hematologic cancer sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Quizartinib (AC220) inhibited growth of transformed hematologic cells expressing FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). 31309543
FLT3 exon 14 ins leukemia sensitive Pexidartinib Preclinical - Cell line xenograft Actionable In a preclinical study, PLX3397 inhibited proliferation of human leukemia cells harboring FLT3-ITD in culture and in cell line xenograft models (PMID: 25847190). 25847190
FLT3 exon 14 ins acute myeloid leukemia sensitive A-1210477 + Venetoclax Preclinical - Cell culture Actionable In a preclinical study, A-1210477 and Venclexta (venetoclax) combination treatment synergistically inhibited viability of acute myeloid leukemia cell lines harboring FLT3 internal tandem duplication (ITD) in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins acute myeloid leukemia sensitive Cytarabine + SKI-G-801 Preclinical - Cell culture Actionable In a preclinical study, the combination of SKI-G-801 and Cytosar-U (cytarabine) resulted in a synergistic effect, demonstrating greater inhibition of proliferation compared to G-749 alone in acute myeloid leukemia cells harboring a FLT3 internal tandem duplication (PMID: 24532805). 24532805
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive Cytarabine + Daunorubicin + Quizartinib Phase I Actionable In a Phase I trial (QuANTUM-First), the combination therapy, Quizartinib (AC220) with Cytosar-U (cytarabine) and Cerubidine (daunorubicin), resulted in 67% (6/9) of acute myeloid leukemia patients harboring a FLT3-ITD achieving a composite complete response and two patients achieving morphologic leukemia-free state (PMID: 29139135; NCT01390337). 29139135
FLT3 exon 14 ins hematologic cancer sensitive GTP-14564 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing a FLT3 internal tandem duplication were sensitive to GTP-14564 treatment in culture, demonstrating decreased Stat5 activity and growth inhibition (PMID: 12815052). 12815052
FLT3 exon 14 ins acute myeloid leukemia sensitive Dubermatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Dubermatinib (TP-0903) treatment resulted in cell cycle arrest and apoptosis, induced differentiation, and inhibited growth of acute myeloid leukemia cell lines harboring a FLT3-ITD mutation in culture, and reduced tumor growth and increased survival in cell line xenograft models (PMID: 33268594). 33268594
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive IACS-13909 Preclinical - Cell line xenograft Actionable In a preclinical study, IACS-13909 decreased Erk phosphorylation in acute myeloid leukemia cells harboring FLT3 exon 14 insertion (ITD) in culture, and inhibited tumor growth and increased overall survival in cell line xenograft models (PMID: 32928921). 32928921
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive Pexidartinib Phase Ib/II Actionable In a Phase I/II trial, treatment with Turalio (pexidartinib) was well-tolerated and resulted in an overall response rate of 21% (19/90) and a composite complete remission (CRc) rate of 11% (10/90) in patients with relapsed/refractory acute myeloid leukemia harboring a FLT3-ITD mutation (PMID: 32330242; NCT01349049). 32330242
FLT3 exon 14 ins acute myeloid leukemia sensitive Daunorubicin + LAM-003 Preclinical - Cell culture Actionable In a preclinical study, LAM-003 and Cerubidine (daunorubicin) combination treatment synergistically reduced viability of acute myeloid leukemia cell lines harboring FLT3 internal tandem duplication (ITD) in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins acute myeloid leukemia sensitive E6201 Preclinical - Cell culture Actionable In a preclinical study, E6201 induced apoptosis in blast samples derived from acute myeloid leukemia patients harboring FLT3 internal tandem duplications (ITD) in culture (PMID: 26822154). 26822154
FLT3 exon 14 ins acute myeloid leukemia not predictive ARQ 531 Preclinical - Patient cell culture Actionable In a preclinical study, ARQ 531 treatment induced apoptosis in acute myeloid leukemia cells harboring either FLT3 exon 14 insertion (FLT3-ITD) or wild-type FLT3, and inhibited proliferation and reduced colony formation in patient cells derived from acute myeloid leukemia independent of FLT3 status in culture (PMID: 31992353). 31992353
FLT3 exon 14 ins acute myeloid leukemia sensitive CG-806 Preclinical - Cell line xenograft Actionable In a preclinical study, CG-806 inhibited FLT3 downstream signaling, resulted in growth inhibition of acute myeloid leukemia cells harboring FLT3 exon 14 insertion (ITD) in culture and tumor inhibition in cell line xenograft models (Clin Cancer Res 2017; 23(24_Suppl):Abstract nr 25). detail... detail...
FLT3 exon 14 ins leukemia sensitive E6201 Preclinical - Cell line xenograft Actionable In a preclinical study, E6201 induced growth inhibition and apoptosis in leukemia cell lines harboring FLT3 internal tandem duplications (ITD) and reduced tumor burden in xenograft models (PMID: 26822154). 26822154
FLT3 exon 14 ins acute myeloid leukemia sensitive LAM-003 + Venetoclax Preclinical - Patient cell culture Actionable In a preclinical study, LAM-003 and Venclexta (venetoclax) combination treatment synergistically induced cell death, and inhibited viability of acute myeloid leukemia cell lines and patient-derived cells harboring FLT3 internal tandem duplication (ITD) in culture, and increased survival in a cell line xenograft model (PMID: 31751472). 31751472
FLT3 exon 14 ins hematologic cancer decreased response Avapritinib Preclinical - Cell culture Actionable In a preclinical study, Ayvakit (avapritinib) inhibited growth of transformed hematologic cells expressing FLT3 exon 14 insertions (ITD) in culture with reduced potency compared to other kinase inhibitors (PMID: 31309543). 31309543
FLT3 exon 14 ins hematologic cancer sensitive Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Nexavar (sorafenib) inhibited growth of transformed hematologic cells expressing FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). 31309543
FLT3 exon 14 ins hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited growth of transformed hematologic cells expressing FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). 31309543
FLT3 exon 14 ins acute myeloid leukemia sensitive Sorafenib Preclinical - Patient cell culture Actionable In a preclinical study, FLT3-ITD mutations correlated with sensitivity to Nexavar (sorafenib) in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). 30333627
FLT3 exon 14 ins acute myeloid leukemia sensitive Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Nexavar (sorafenib) inhibited Flt3 phosphorylation and growth of acute myeloid leukemia cell lines harboring FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). 31309543
FLT3 exon 14 ins acute myeloid leukemia sensitive Gilteritinib + LAM-003 Preclinical - Cell culture Actionable In a preclinical study, LAM-003 and Xospata (gilteritinib) combination treatment reduced viability of acute myeloid leukemia cell lines harboring FLT3 internal tandem duplication (ITD) in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins acute myeloid leukemia sensitive Azacitidine + Sorafenib Guideline Actionable Nexavar (sorafenib) in combination with Vidaza (azacitidine) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org). detail...
FLT3 exon 14 ins Advanced Solid Tumor sensitive LAM-003 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3 internal tandem duplication (ITD) demonstrated sensitivity to LAM-003 treatment in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins hematologic cancer sensitive LT-171-861 Preclinical - Cell culture Actionable In a preclinical study, LT-171-861 inhibited cell viability and decreased FLT3 phosphorylation in transformed hematologic cells expressing a FLT3-ITD mutation in culture (PMID: 33391463). 33391463
FLT3 exon 14 ins Advanced Solid Tumor sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) demonstrated efficacy in inhibiting proliferation and viability of transformed cells expressing a FLT3-ITD mutation in culture (PMID: 12124173). 12124173
FLT3 exon 14 ins acute myeloid leukemia sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib inhibited Flt3 phosphorylation and growth of acute myeloid leukemia cell lines harboring FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). 31309543
FLT3 exon 14 ins acute myeloid leukemia sensitive Crenolanib Phase I Actionable In a Phase I trial, Crenolanib treatment resulted in an overall survival (OS) of 238 days in AML patients harboring FLT3 exon 14 insertions (ITD) that received no prior therapy, and an OS of 158 days in those progressed on TKIs (J Clin Oncol 34, 2016 (suppl; abstr 7008)). detail...
FLT3 exon 14 ins acute myeloid leukemia sensitive Crenolanib Preclinical - Patient cell culture Actionable In a preclinical study, FLT3-ITD mutations correlated with sensitivity to Crenolanib in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). 30333627
FLT3 exon 14 ins acute myeloid leukemia sensitive Ponatinib Phase I Actionable In a Phase I trial, Iclusig (ponatinib) resulted in a 25% (3/12) overall response rate, indicated as partial remission or better, in acute myeloid leukemia patients harboring FLT3-ITD (PMID: 23691988). 23691988
FLT3 exon 14 ins acute myeloid leukemia sensitive Ponatinib Preclinical - Patient cell culture Actionable In a preclinical study, Iclusig (ponatinib) inhibited viability of patient derived acute myeloid leukemia cells harboring FLT3 ITD mutations in culture, and inhibited growth of tumors in cell line xenograft models (PMID: 21482694). 21482694
FLT3 exon 14 ins acute myeloid leukemia sensitive FF-10101 Preclinical - Pdx & cell culture Actionable In a preclinical study, FF-10101 inhibited Flt3 autophosphorylation and cell growth of leukemic cells in culture and in AML-patient-derived xenograft models with FLT3-ITD mutations (PMID: 29187377). 29187377
FLT3 exon 14 ins acute myeloid leukemia conflicting Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited Flt3 phosphorylation and growth of acute myeloid leukemia cell lines harboring FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). 31309543
FLT3 exon 14 ins acute myeloid leukemia conflicting Midostaurin Preclinical - Cell culture Actionable In a preclinical study, co-culturing human stromal cells with an acute myeloid cell line harboring a FLT3 internal tandem duplication (ITD) demonstrated resistance to Rydapt (midostaurin) treatment in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins acute myeloid leukemia sensitive Altiratinib Preclinical - Cell culture Actionable In a preclinical study, Altiratinib (DCC-0701) inhibited proliferation of an acute myeloid leukemia cell harboring a FLT3-ITD mutation in culture (PMID: 26285778). 26285778
FLT3 exon 14 ins myelodysplastic syndrome not applicable N/A Guideline Prognostic FLT3 internal tandem duplication (FLT3-ITD) mutations are associated with poor prognosis in patients with myelodysplastic syndrome (NCCN.org). detail...
FLT3 exon 14 ins Advanced Solid Tumor sensitive Pexidartinib Preclinical Actionable In a preclinical study, PLX3397 inhibited proliferation of transformed cells expressing FLT3-ITD in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins hematologic cancer sensitive HQP1351 Preclinical - Cell culture Actionable In a preclinical study, GZD824 (HQP1351) inhibited growth of transformed cells expressing FLT3-ITD in culture (PMID: 32247263). 32247263
FLT3 exon 14 ins acute myeloid leukemia not applicable N/A Guideline Prognostic FLT3 internal tandem duplication (FLT3-ITD) mutations are associated with inferior prognosis in acute myeloid leukemia patients with normal karyotype (NCCN.org). detail...
FLT3 exon 14 ins hematologic cancer sensitive Dubermatinib Preclinical - Cell culture Actionable In a preclinical study, Dubermatinib (TP-0903) inhibited growth of transformed cells expressing a FLT3-ITD mutation in culture (PMID: 33268594). 33268594
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive Pacritinib Preclinical - Cell line xenograft Actionable In a preclinical study, Pacritinib (SB1518) induced apoptosis and inhibited proliferation of acute myeloid leukemia cells harboring a FLT3-ITD mutation in culture, and inhibited tumor growth and induced tumor regression in cell line xenograft models (PMID: 22829080). 22829080
FLT3 exon 14 ins acute myeloid leukemia sensitive UNC1666 Preclinical - Cell culture Actionable In a preclinical study, UNC1666 inhibited FLT3 phosphorylation and downstream signaling, induced apoptosis of acute myeloid leukemia cells harboring FLT3 exon 14 insertions (ITD) in culture (PMID: 25762638). 25762638
FLT3 exon 14 ins acute myeloid leukemia sensitive HQP1351 Preclinical - Cell line xenograft Actionable In a preclinical study, GZD824 (HQP1351) reduced Flt3 and Stat5 phosphorylation, induced cell cycle arrest and apoptosis, and inhibited growth of acute myeloid leukemia cells harboring FLT3-ITD in culture, and suppressed tumor growth, decreased Flt3 activation, and induced apoptosis in cell line xenograft models (PMID: 32247263). 32247263
FLT3 exon 14 ins acute myeloid leukemia sensitive Cytarabine + LAM-003 Preclinical - Cell culture Actionable In a preclinical study, LAM-003 and Cytosar-U (cytarabine) combination treatment synergistically reduced viability of an acute myeloid leukemia cell line harboring FLT3 internal tandem duplication (ITD) in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive SHP099 Preclinical - Pdx Actionable In a preclinical study, treatment with SHP099 resulted in reduction of CD45-positive leukemic cells and decreased splenomegaly in a human primary tumor-derived xenograft model of acute myeloid leukemia harboring a FLT3-ITD mutation (PMID: 27362227). 27362227
FLT3 exon 14 ins acute myeloid leukemia sensitive Selinexor + Sorafenib Phase Ib/II Actionable In a Phase I/II trial, combination of Selinexor and Nexavar (sorafenib) treatment resulted in complete remission in 29% (4/14) and more than 50% blast reduction in 14% (2/14) of patients with acute myeloid leukemia harboring FLT3 ITD and/or D835 mutations (ASH, 59th Annual Meeting and Exposition, Dec 2017, Abstract 1344; NCT01607892). detail...
FLT3 exon 14 ins leukemia predicted - sensitive GMI-1359 + Sorafenib Preclinical - Cell culture Actionable In a preclinical study, combination of GMI-1359 with Nexavar (sorafenib) enhanced apoptosis compared to Nexavar (sorafenib) alone (48.9% vs 36.6%) in leukemia cell lines harboring FLT3 internal tandem duplication (ITD) mutations (Blood 2015 126(23):3790). detail...
FLT3 exon 14 ins acute myeloid leukemia sensitive LAM-003 Preclinical - Patient cell culture Actionable In a preclinical study, LAM-003 treatment inhibited colony formation, and reduced viability of acute myeloid cell lines harboring FLT3 internal tandem duplication (ITD) in the presence of stromal factors that confer resistance to Xospata (gilteritinib) and Crenolanib, and induced apoptosis in patient-derived cells in culture, and induced tumor regression, and increased survival in cell line xenograft models (PMID: 31751472). 31751472
FLT3 exon 14 ins acute myeloid leukemia sensitive SKI-G-801 Preclinical - Cell line xenograft Actionable In a preclinical study, SKI-G-801 induced apoptosis in acute myeloid leukemia cells harboring a FLT3 internal tandem duplication in culture, and inhibited tumor growth and induced tumor regression in cell line xenograft models (PMID: 24532805). 24532805
FLT3 exon 14 ins hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib inhibited growth of transformed hematologic cells expressing FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). 31309543
FLT3 exon 14 ins acute myeloid leukemia sensitive GTP-14564 Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication were sensitive to GTP-14564 treatment in culture, demonstrating growth inhibition (PMID: 12815052). 12815052
FLT3 exon 14 ins acute myeloid leukemia sensitive Ipatasertib + Palbociclib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Ibrance (palbociclib) and Alisertib (MLN8237) resulted in a synergistic effect in acute myeloid leukemia cells expressing a FLT3-ITD, demonstrating a greater reduced cell viability compared to either agent alone (PMID: 30544932). 30544932
FLT3 exon 14 ins acute myeloid leukemia sensitive Cytarabine + LT-171-861 Preclinical - Cell culture Actionable In a preclinical study, the combination of LT-171-861 and Cytosar-U (cytarabine) synergistically inhibited cell viability in acute myeloid leukemia cell lines harboring FLT3-ITD mutations in culture (PMID: 33391463). 33391463
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive Azacitidine + Quizartinib Phase Ib/II Actionable In a Phase I/II trial, Quizartinib (AC220) in combination with Vidaza (azacitidine) resulted in a median overall survival of 13.4 months and a median progression-free survival of 6.9 months in acute myeloid leukemia patients harboring FLT3 ITD mutations (ASH 59th Annual Meeting and Exposition, Dec 2017, Abstract 723). detail...
FLT3 exon 14 ins acute myeloid leukemia sensitive PD-0325901 + Sorafenib Preclinical - Patient cell culture Actionable In a preclinical study, Nexavar (sorafenib) and PD-0325901 synergistically induced apoptosis and inhibited proliferation of acute myeloid leukemia (AML) cell lines harboring FLT3 internal tandem duplication (ITD) mutations in culture, inhibited Erk phosphorylation in FLT3-ITD mutant AML patient cells, and reduced leukemic burden in a FLT3-ITD mutant AML cell line xenograft model (PMID: 28923853). 28923853
FLT3 exon 14 ins acute myeloid leukemia sensitive Abivertinib + Omacetaxine mepesuccinate Preclinical - Patient cell culture Actionable In a preclinical study, Abivertinib (AC0010) treatment in combination with Synribo (omacetaxine mepesuccinate) enhanced apoptosis and reduced viability of acute myeloid leukemia (AML) cells harboring FLT3 exon 14 insertion, and enhanced reduction in viability of patient-derived AML cells harboring FLT3 exon 14 insertion in culture, and enhanced reduction in tumor burden and increased survival in cell line xenograft models compared to either agents alone (PMID: 31310800). 31310800
FLT3 exon 14 ins acute myeloid leukemia sensitive Semaxanib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication were sensitive to Semaxanib (SU5416) in culture, demonstrating inhibition of cell proliferation and inhibition of Flt3, Mapk, and Stat5 phosphorylation (PMID: 12351406). 12351406
FLT3 exon 14 ins Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing FLT3 ITD in culture (PMID: 27780853). 27780853
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive Ibrutinib Preclinical - Cell culture Actionable In a preclinical study, Imbruvica (ibrutinib) treatment reduced viability of acute myeloid leukemia cells harboring FLT3 exon 14 insertion, however, with decreased response compared to cells treated with Abivertinib (AC0010) in culture (PMID: 31310800). 31310800
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive Ibrutinib Preclinical - Patient cell culture Actionable In a preclinical study, FLT3-ITD mutations correlated with sensitivity to Imbruvica (ibrutinib) in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). 30333627
FLT3 exon 14 ins hematologic cancer sensitive Palbociclib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3 ITD were sensitive to treatment with Ibrance (palbociclib), demonstrating inhibition of cell growth in culture (PMID: 30544932). 30544932
FLT3 exon 14 ins acute myeloid leukemia sensitive Sorafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, Nexavar (sorafenib) combined with Mekinist (trametinib) enhanced apoptosis in acute myeloid leukemia cell lines harboring FLT3 internal tandem duplication (ITD) mutations in culture (PMID: 28923853). 28923853
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive Cytarabine + Quizartinib Phase Ib/II Actionable In a Phase I/II trial, Quizartinib (AC220) in combination with Cytosar-U (cytarabine) resulted in a median overall survival of 6.7 months and a median progression-free survival of 3 months in acute myeloid leukemia patients harboring FLT3 ITD mutations (ASH 59th Annual Meeting and Exposition, Dec 2017, Abstract 723). detail...
FLT3 exon 14 ins acute myeloid leukemia sensitive Tandutinib Preclinical - Cell culture Actionable In a preclinical study, Tandutinib (CT53518) treatment inhibited viability of an acute myeloid leukemia cell line harboring FLT3 internal tandem duplication (ITD) in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins acute myeloid leukemia resistant Avapritinib Preclinical - Cell culture Actionable In a preclinical study, Ayvakit (avapritinib) did not inhibit Flt3 phosphorylation or growth of acute myeloid leukemia cell lines harboring FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). 31309543
FLT3 exon 14 ins hematologic cancer sensitive KW-2449 Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD were sensitive to treatment with KW-2449, demonstrating growth inhibition in culture (PMID: 22858906). 22858906
FLT3 exon 14 ins acute myeloid leukemia sensitive Alisertib + Palbociclib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Ibrance (palbociclib) and Alisertib (MLN8237) resulted in a synergistic effect in acute myeloid leukemia cells expressing a FLT3-ITD, demonstrating a greater reduced cell viability compared to either agent alone (PMID: 30544932). 30544932
FLT3 exon 14 ins acute myeloid leukemia sensitive Ki23819 Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication were sensitive to Ki23819 in culture, demonstrating inhibition of autophosphorylation and downstream signaling, and reduced cell proliferation (PMID: 15815726). 15815726
FLT3 exon 14 ins acute myeloid leukemia sensitive MK2206 + Palbociclib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Ibrance (palbociclib) and MK2206 resulted in a synergistic effect in acute myeloid leukemia cells expressing a FLT3-ITD, demonstrating a greater reduced cell viability compared to either agent alone (PMID: 30544932). 30544932
FLT3 exon 14 ins acute myeloid leukemia sensitive MK2206 + Venetoclax Preclinical - Cell culture Actionable In a preclinical study, MK2206 and Venclexta (venetoclax) combination treatment synergistically induced cell death of acute myeloid leukemia cell lines harboring FLT3 internal tandem duplication (ITD) in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins acute myeloid leukemia sensitive Quizartinib Phase II Actionable In a Phase II trial, Quizartinib (AC220) treatment resulted in a composite complete remission (CCR) in 56% (63/112; 3 complete remission (CR)) of FLT3-ITD-positive patients vs. 36% (16/44; 1 CR) of FLT3-ITD-negative patients with relapsed/refractory acute myeloid leukemia (AML) after first-line therapy, and CCR in 46% (62/136; 5 CR) of FLT3-ITD-positive vs. 30% (12/40; 1 CR) in FLT3-ITD-negative patients with relapsed/refractory AML after salvage chemotherapy or transplant (PMID: 29859851; NCT00989261). 29859851
FLT3 exon 14 ins acute myeloid leukemia sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Quizartinib (AC220) inhibited proliferation of several acute myeloid leukemia cell lines harboring different FLT3-ITD mutations in culture (PMID: 28895560). 28895560
FLT3 exon 14 ins acute myeloid leukemia sensitive Quizartinib Phase I Actionable In a Phase I trial, acute myeloid leukemia (AML) pediatric patients harboring a FLT3-ITD mutation demonstrated a greater sensitivity to treatment with Quizartinib (AC220) when compared to AML patients with wild-type FLT3, resulting in three complete responses, four with stable disease, and a lower bone marrow blast cell count (PMID: 26920889). 26920889
FLT3 exon 14 ins acute myeloid leukemia sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Quizartinib (AC220) inhibited Flt3 phosphorylation and growth of acute myeloid leukemia cell lines harboring FLT3_OT exon 14 insertions (ITD) in culture (PMID: 31309543). 31309543
FLT3 exon 14 ins acute myeloid leukemia no benefit Rebastinib Phase I Actionable In a Phase I trial, acute myeloid leukemia patients harboring a FLT3 internal tandem duplication did not benefit from treatment with Rebastinib (DCC-2036) (PMID: 27927766). 27927766
FLT3 exon 14 ins acute myeloid leukemia sensitive ENMD-2076 Phase I Actionable In a Phase I trial, an acute myeloid leukemia patient with a FLT3-ITD mutation demonstrated anti-leukemia activity when treated with ENMD-2076 (PMID: 27406088). 27406088
FLT3 exon 14 ins acute myeloid leukemia sensitive Cytarabine + Daunorubicin + Midostaurin FDA approved - On Companion Diagnostic Actionable In a Phase III trial that supported FDA approval, treatment with Rydapt (midostaurin), combined with Cytosar-U (cytarabine) and Daunorubicin, improved overall survival (74.7 mo vs 25.6 mo) in patients with FLT3-mutant (D835X and I836X) or FLT3-ITD (exon 14 insertions) acute myeloid leukemia compared to Cytosar-U (cytarabine) and Daunorubicin with placebo (PMID: 28644114). 28644114 detail... detail...
FLT3 exon 14 ins acute myeloid leukemia sensitive ARQ 531 + Venetoclax Preclinical - Cell line xenograft Actionable In a preclinical study, ARQ 531 treatment in combination with Venclexta (venetoclax) synergistically inhibited proliferation of acute myeloid leukemia cells harboring FLT3 exon 14 insertion (FLT3-ITD) in culture, and reduced tumor burden, and increased survival in a disseminated cell line xenograft model of acute myeloid leukemia compared to either agents alone (PMID: 31992353). 31992353
FLT3 exon 14 ins FLT3 F691L Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing FLT3 ITD and F691L in culture (PMID: 27780853). 27780853
FLT3 exon 14 ins FLT3 F691L hematologic cancer decreased response Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing both FLT3 exon 14 insertions (ITD) and FLT3 F691L were less sensitive to Quizartinib (AC220)-induced growth inhibition compared to cells expressing FLT3 ITD in culture (PMID: 31309543). 31309543
FLT3 exon 14 ins FLT3 F691L Advanced Solid Tumor sensitive LAM-003 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3 internal tandem duplication (ITD) and FLT3 F691L demonstrated sensitivity to LAM-003 treatment in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins FLT3 F691L hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited growth of transformed hematologic cells expressing both FLT3 exon 14 insertions (ITD) and FLT3 F691L in culture (PMID: 31309543). 31309543
FLT3 exon 14 ins FLT3 F691L hematologic cancer resistant KW-2449 Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 F691L were resistant to treatment with KW-2449 in culture (PMID: 22858906). 22858906
FLT3 exon 14 ins FLT3 F691L hematologic cancer decreased response Avapritinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing both FLT3 exon 14 insertions (ITD) and FLT3 F691L were less sensitive to Ayvakit (avapritinib)-induced growth inhibition compared to cells expressing FLT3 ITD in culture (PMID: 31309543). 31309543
FLT3 exon 14 ins FLT3 F691L hematologic cancer sensitive SKI-G-801 Preclinical - Cell culture Actionable In a preclinical study, cells co-expressing a FLT3 internal tandem duplication and FLT3 F691L were sensitive to SKI-G-801 in culture, demonstrating inhibition of cell growth and inhibition of Flt3 autophosphorylation (PMID: 24532805). 24532805
FLT3 exon 14 ins FLT3 F691L hematologic cancer resistant Sorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing both FLT3 exon 14 insertions (ITD) and FLT3 F691L were resistant to Nexavar (sorafenib)-induced growth inhibition in culture (PMID: 31309543). 31309543
FLT3 exon 14 ins FLT3 F691L acute myeloid leukemia sensitive FF-10101 Preclinical - Cell line xenograft Actionable In a preclinical study, FF-10101 inhibited Flt3 autophosphorylation and growth of leukemic cell lines and inhibited growth of cell line xenografts with FLT3-ITD/F691L compound mutations (PMID: 29187377). 29187377
FLT3 exon 14 ins FLT3 F691L acute myeloid leukemia sensitive MRX-2843 Preclinical - Cell line xenograft Actionable In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant acute myeloid leukemia cells harboring FLT3 internal tandem duplication (ITD) and F691L in culture, and prolonged survival in cell line xenograft models (PMID: 27158668). 27158668
FLT3 exon 14 ins FLT3 F691L hematologic cancer predicted - sensitive HM43239 Preclinical Actionable In a preclinical study, HM43239 treatment inhibited transformed cells expressing FLT3 ITD and F691L in cell culture (Cancer Res 2019;79(13 Suppl):Abstract nr 1293). detail...
FLT3 exon 14 ins FLT3 F691L myeloid leukemia resistant A-419259 Preclinical - Cell culture Actionable In a preclinical study, transformed myeloid leukemia cells co-expressing FLT-ITD and FLT3 F691L demonstrated resistance to A-419259 treatment in culture (PMID: 31790499). 31790499
FLT3 exon 14 ins FLT3 F691L leukemia sensitive E6201 Preclinical Actionable In a preclinical study, E6201 inhibited proliferation and induced apoptosis in FLT3 inhibitor-resistant leukemia cell lines harboring FLT3 F691L in addition to FLT3 internal tandem duplications (ITD) in culture (PMID: 26822154). 26822154
FLT3 exon 14 ins FLT3 F691L acute myeloid leukemia decreased response Lestaurtinib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 F691L demonstrated a decreased response to Lestaurtinib (CEP-701) compared to treated cells harboring a FLT3 ITD and expressing FLT3 Y842C (Blood 2009 114:3776). detail...
FLT3 exon 14 ins FLT3 F691L hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited growth of transformed hematologic cells expressing both FLT3 exon 14 insertions (ITD) and FLT3 F691L in culture (PMID: 31309543). 31309543
FLT3 exon 14 ins FLT3 F691L Advanced Solid Tumor resistant Sorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and F691L were resistant to Nexavar (sorafenib) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 F691L hematologic cancer sensitive Dubermatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Dubermatinib (TP-0903) treatment decreased phosphorylation of Flt3 and Stat5 and inhibited growth of transformed cells expressing a FLT3-ITD mutation and FLT3 F691L in culture, and reduced peripheral blood tumor burden in cell line xenograft models (PMID: 33268594). 33268594
FLT3 exon 14 ins FLT3 F691L leukemia predicted - sensitive CG-806 Preclinical - Cell culture Actionable In a preclinical study, CG-806 inhibited FLT3 downstream signaling, resulted in growth inhibition in leukemia cells expressing FLT3 exon 14 insertion (ITD) mutation and F691L in culture (Clin Cancer Res 2017; 23(24_Suppl):Abstract nr 25). detail...
FLT3 exon 14 ins FLT3 F691L Advanced Solid Tumor sensitive MRX-2843 Preclinical - Cell culture Actionable In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant transformed cells over expressing both FLT3 internal tandem duplication (ITD) and F691L in culture (PMID: 27158668). 27158668
FLT3 exon 14 ins FLT3 F691L hematologic cancer sensitive LT-171-861 Preclinical - Cell line xenograft Actionable In a preclinical study, LT-171-861 inhibited cell viability and decreased FLT3 phosphorylation in transformed hematologic cells expressing a FLT3-ITD mutation and FLT3 F691L in culture, and inhibited tumor growth and prolonged survival in cell line xenograft models (PMID: 33391463). 33391463
FLT3 exon 14 ins FLT3 F691L leukemia sensitive Pexidartinib Preclinical Actionable In a preclinical study, PLX3397 inhibited proliferation of human leukemia cells harboring both FLT3-ITD and FLT3 F691L in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L acute myeloid leukemia decreased response Midostaurin Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 F691L demonstrated a decreased response to Lestaurtinib (CEP-701) compared to treated cells harboring a FLT3 ITD and expressing FLT3 Y842C (Blood 2009 114:3776). detail...
FLT3 exon 14 ins FLT3 F691L Advanced Solid Tumor sensitive Pexidartinib Preclinical Actionable In a preclinical study, PLX3397 inhibited growth of transformed cells expressing a compound FLT3 F691L/FLT3-ITD mutation in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L Advanced Solid Tumor resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and F691L were resistant to Quizartinib (AC220) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 F691L hematologic cancer decreased response Crenolanib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing both FLT3 exon 14 insertions (ITD) and FLT3 F691L were less sensitive to Crenolanib-induced growth inhibition compared to cells expressing FLT3 ITD in culture (PMID: 31309543). 31309543
FLT3 exon 14 ins FLT3 D835Y leukemia predicted - resistant Pexidartinib Case Reports/Case Series Actionable In a clinical case study, a patient with FLT3-ITD positive leukemia initially responded to Pexidartinib (PLX3397) therapy, but experienced relapse after emergence of FLT3 D835Y on the same allele as the FLT3-ITD mutation (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D835Y hematologic cancer no benefit Palbociclib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing FLT3 ITD and FLT3 D835Y did not respond to treatment with Ibrance (palbociclib) in culture (PMID: 30544932). 30544932
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia sensitive MRX-2843 Preclinical - Cell line xenograft Actionable In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant acute myeloid leukemia cells harboring FLT3 internal tandem duplication (ITD) and D835Y in culture, and prolonged survival in cell line xenograft models (PMID: 27158668). 27158668
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia predicted - sensitive Crenolanib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835Y demonstrated sensitivity to Crenolanib (CP-868596) treatment in culture, resulting in reduced cell viability (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 D835Y hematologic cancer predicted - sensitive HQP1351 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 D835Y demonstrated decreased proliferation in response to GZD824 (HQP1351) in culture, but were less sensitive to treatment than cells co-expressing FLT3-ITD with other FLT3 kinase domain mutations (PMID: 32247263). 32247263
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia sensitive Dubermatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Dubermatinib (TP-0903) treatment resulted in cell cycle arrest and apoptosis, induced differentiation, and inhibited growth of acute myeloid leukemia cells harboring a FLT3-ITD mutation and FLT3 D835Y in culture, and reduced tumor growth and increased survival in cell line xenograft models (PMID: 33268594). 33268594
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia predicted - sensitive Gilteritinib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835Y demonstrated sensitivity to Xospata (gilteritinib) treatment in culture, resulting in reduced cell viability (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia predicted - sensitive Gilteritinib Preclinical - Cell line xenograft Actionable In a preclinical study, Xospata (gilteritinib) treatment inhibited growth of acute myeloid leukemia cells harboring a FLT3-ITD mutation and FLT3 D835Y in culture, and reduced tumor growth and increased survival in cell line xenograft models (PMID: 33268594). 33268594
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia sensitive LAM-003 Preclinical - Patient cell culture Actionable In a preclinical study, LAM-003 treatment inhibited viability of an acute myeloid leukemia cell line and patient-derived cells harboring FLT3 internal tandem duplication (ITD) and FLT3 D835Y in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia resistant Tandutinib Preclinical - Cell culture Actionable In a preclinical study, an acute myeloid cell line harboring FLT3 internal tandem duplication (ITD) and FLT3 D835Y demonstrated resistance to Tandutinib (CT53518) treatment in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins FLT3 D835Y hematologic cancer predicted - sensitive HM43239 Preclinical Actionable In a preclinical study, HM43239 treatment inhibited transformed cells expressing FLT3 ITD and D835Y in cell culture (Cancer Res 2019;79(13 Suppl):Abstract nr 1293). detail...
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia resistant Sorafenib Case Reports/Case Series Actionable In a clinical case study, FLT3 D835Y was identified as an acquired resistance mutation in a patient with acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD) whose disease progressed on Nexavar (sorafenib) after initial response (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia resistant Sorafenib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835Y demonstrated resistance to Nexavar (sorafenib) treatment in culture (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia resistant Sorafenib Preclinical - Cell culture Actionable In a preclinical study, an acute myeloid cell line harboring FLT3 internal tandem duplication (ITD) and FLT3 D835Y did not demonstrate sensitivity to Nexavar (sorafenib) treatment in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins FLT3 D835Y Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, FLT3 D835Y conferred resistance to PLX3397 when expressed in a compound mutation with FLT3-ITD in cell culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D835Y Advanced Solid Tumor sensitive MRX-2843 Preclinical - Cell culture Actionable In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant transformed cells over expressing both FLT3 internal tandem duplication (ITD) and D835Y in culture (PMID: 27158668). 27158668
FLT3 exon 14 ins FLT3 D835Y leukemia predicted - sensitive CG-806 Preclinical - Cell culture Actionable In a preclinical study, CG-806 inhibited FLT3 downstream signaling, resulted in growth inhibition in leukemia cells expressing FLT3 exon 14 insertion (ITD) mutation and D835Y in culture (Clin Cancer Res 2017; 23(24_Suppl):Abstract nr 25). detail...
FLT3 exon 14 ins FLT3 D835Y myeloid leukemia resistant A-419259 Preclinical - Cell culture Actionable In a preclinical study, transformed myeloid leukemia cells co-expressing FLT-ITD and FLT3 D835Y demonstrated resistance to A-419259 treatment in culture (PMID: 31790499). 31790499
FLT3 exon 14 ins FLT3 D835Y Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing FLT3 ITD and D835Y in culture (PMID: 27780853). 27780853
FLT3 exon 14 ins FLT3 D835Y hematologic cancer sensitive Dubermatinib Preclinical - Cell culture Actionable In a preclinical study, Dubermatinib (TP-0903) inhibited growth of transformed cells expressing a FLT3-ITD mutation and FLT3 D835Y in culture (PMID: 33268594). 33268594
FLT3 exon 14 ins FLT3 D835Y hematologic cancer no benefit Danusertib + Palbociclib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing FLT3 ITD and FLT3 D835Y did not respond to the combination treatment of Ibrance (palbociclib) and Danusertib (PHA-739358) in culture (PMID: 30544932). 30544932
FLT3 exon 14 ins FLT3 D835Y hematologic cancer predicted - sensitive LT-171-861 Preclinical - Cell culture Actionable In a preclinical study, LT-171-861 inhibited cell viability and decreased FLT3 phosphorylation in transformed hematologic cells expressing a FLT3-ITD mutation and FLT3 D835Y in culture (PMID: 33391463). 33391463
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia predicted - resistant Midostaurin Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835Y demonstrated resistance to Rydapt (midostaurin) treatment in culture (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia sensitive FF-10101 Preclinical - Cell line xenograft Actionable In a preclinical study, FF-10101 inhibited Flt3 autophosphorylation and growth of leukemic cell lines and inhibited growth of cell line xenografts with FLT3-ITD/D835Y compound mutations (PMID: 29187377). 29187377
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia predicted - resistant Quizartinib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835Y demonstrated resistance to Vanflyta (Quizartinib) treatment in culture (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 D835V Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D835V were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D835V Advanced Solid Tumor sensitive MRX-2843 Preclinical - Cell culture Actionable In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant transformed cells over expressing both FLT3 internal tandem duplication (ITD) and D835V in culture (PMID: 27158668). 27158668
FLT3 exon 14 ins FLT3 D835V hematologic cancer predicted - sensitive HQP1351 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 D835V demonstrated decreased proliferation in response to GZD824 (HQP1351) in culture, but were less sensitive to treatment than cells co-expressing FLT3-ITD with other FLT3 kinase domain mutations (PMID: 32247263). 32247263
FLT3 exon 14 ins FLT3 D835F Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D835F were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D835F acute myeloid leukemia predicted - resistant Sorafenib Case Reports/Case Series Actionable In a clinical case study, FLT3 D835F was identified as an acquired resistance mutation in a patient with acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD) whose disease progressed on Nexavar (sorafenib) after initial response (PMID: 24227820). 24227820
FLT3 exon 14 ins FLT3 D835F acute myeloid leukemia predicted - sensitive Crenolanib Preclinical - Patient cell culture Actionable In a preclinical study, Crenolanib inhibited growth of blasts derived from a patient with acute myeloid leukemia harboring FLT3 internal tandem duplication (ITD) and FLT3 D835F (PMID: 24227820). 24227820
FLT3 exon 14 ins FLT3 D835F Advanced Solid Tumor sensitive MRX-2843 Preclinical - Cell culture Actionable In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant transformed cells over expressing both FLT3 internal tandem duplication (ITD) and D835F in culture (PMID: 27158668). 27158668
FLT3 exon 14 ins FLT3 Y842H Advanced Solid Tumor decreased response Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and Y842H demonstrated reduced sensitivity to Quizartinib (AC220) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 Y842H Advanced Solid Tumor sensitive MRX-2843 Preclinical - Cell culture Actionable In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant transformed cells over expressing both FLT3 internal tandem duplication (ITD) and Y842H in culture (PMID: 27158668). 27158668
FLT3 exon 14 ins FLT3 Y842H hematologic cancer sensitive HQP1351 Preclinical - Cell culture Actionable In a preclinical study, GZD824 (HQP1351) inhibited growth of transformed cells expressing FLT3-ITD and FLT3 Y842H in culture (PMID: 32247263). 32247263
FLT3 exon 14 ins FLT3 Y842H hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101, as compared to Quizartinib, inhibited Flt3 autophosphorylation and cell proliferation of transformed 32Dcl3 murine myeloid cells expressing a human FLT3-ITD/Y842H compound mutation (PMID: 29187377). 29187377
FLT3 exon 14 ins FLT3 Y842H Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD with FLT3 Y842H were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 Y842H Advanced Solid Tumor decreased response Sorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and Y842H demonstrated reduced sensitivity to Nexavar (sorafenib) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 Y842C Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, FLT3 Y842C conferred resistance to PLX3397 when expressed in a compound mutation with FLT3-ITD in cell culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 Y842C acute myeloid leukemia sensitive Lestaurtinib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 Y842C demonstrated sensitivity to Lestaurtinib (CEP-701) in culture (Blood 2009 114:3776). detail...
FLT3 exon 14 ins FLT3 Y842C hematologic cancer resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 Y842C were resistant to treatment with Vanflyta (Quizartinib) in culture (PMID: 22858906). 22858906
FLT3 exon 14 ins FLT3 Y842C hematologic cancer sensitive LT-171-861 Preclinical - Cell culture Actionable In a preclinical study, LT-171-861 inhibited cell viability and decreased FLT3 phosphorylation in transformed hematologic cells expressing a FLT3-ITD mutation and FLT3 Y842C in culture (PMID: 33391463). 33391463
FLT3 exon 14 ins FLT3 Y842C leukemia sensitive E6201 Preclinical Actionable In a preclinical study, E6201 inhibited proliferation and induced apoptosis in FLT3 inhibitor-resistant leukemia cell lines harboring FLT3 Y842C in addition to FLT3 internal tandem duplications (ITD) in culture (PMID: 26822154). 26822154
FLT3 exon 14 ins FLT3 Y842C hematologic cancer resistant KW-2449 Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 Y842C were resistant to treatment with KW-2449 in culture (PMID: 22858906). 22858906
FLT3 exon 14 ins FLT3 Y842C acute myeloid leukemia resistant Sorafenib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 Y842C demonstrated resistance to Nexavar (sorafenib) in culture (Blood 2009 114:3776). detail...
FLT3 exon 14 ins FLT3 Y842C acute myeloid leukemia sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 Y842C demonstrated sensitivity to Rydapt (midostaurin) in culture (Blood 2009 114:3776). detail...
FLT3 exon 14 ins FLT3 Y842C acute myeloid leukemia resistant AGL2043 Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 Y842C demonstrated resistance to AGL2043 in culture (Blood 2009 114:3776). detail...
FLT3 exon 14 ins FLT3 Y842C acute myeloid leukemia resistant Sunitinib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 Y842C demonstrated resistance to Sutent (sunitinib) in culture (Blood 2009 114:3776). detail...
FLT3 exon 14 ins FLT3 Y842C hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101, as compared to Quizartinib, inhibited Flt3 autophosphorylation and cell proliferation of transformed 32Dcl3 murine myeloid cells expressing a human FLT3-ITD/Y842C compound mutation (PMID: 29187377). 29187377
FLT3 exon 14 ins FLT3 Y842C Advanced Solid Tumor sensitive MRX-2843 Preclinical - Cell culture Actionable In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant transformed cells over expressing both FLT3 internal tandem duplication (ITD) and Y842C in culture (PMID: 27158668). 27158668
FLT3 exon 14 ins FLT3 R834Q Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD with FLT3 R834Q were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L FLT3 R834Q Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691Q/R834Q mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D835E Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D835E were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L FLT3 D835E Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3 ITD with R834Q and F691L were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D835H Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, FLT3 D835H conferred resistance to PLX3397 in transformed cells when expressed as a compound mutation with FLT3-ITD in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D835H leukemia resistant Pexidartinib Clinical Study Actionable In a clinical study, a patient with FLT3-ITD positive leukemia initially responded to PLX3397, but experienced relapse after emergence of a FLT3 D835H mutation on the same allele as the FLT3-ITD mutation (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D835H hematologic cancer sensitive Dubermatinib Preclinical - Cell culture Actionable In a preclinical study, Dubermatinib (TP-0903) inhibited growth of transformed cells expressing a FLT3-ITD mutation and FLT3 D835H in culture (PMID: 33268594). 33268594
FLT3 exon 14 ins FLT3 D835H acute myeloid leukemia sensitive FF-10101 Preclinical - Pdx Actionable In a preclinical study, FF-10101 inhibited cell growth in AML-patient-derived xenograft models with FLT3-ITD/D835H compound mutations (PMID: 29187377). 29187377
FLT3 exon 14 ins FLT3 F691L FLT3 D835H Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/D835H mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D835N hematologic cancer sensitive HQP1351 Preclinical - Cell culture Actionable In a preclinical study, GZD824 (HQP1351) inhibited growth of transformed cells expressing FLT3-ITD and FLT3 D835N in culture (PMID: 32247263). 32247263
FLT3 exon 14 ins FLT3 D835N Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D835N were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L FLT3 D835N Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/D835N mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L FLT3 D839G Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD /F691L/D839G mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D839G Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, FLT3 D835G conferred resistance to PLX3397 when expressed in a compound mutation with FLT3-ITD in cell culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D839H Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D839H were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L FLT3 Y842C Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/Y842C mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L FLT3 Y842H Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/Y842H mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 M837G FLT3 S838R FLT3 D839H leukemia predicted - resistant Pexidartinib Case Reports/Case Series Actionable In a clinical case study, a leukemia patient with FLT3-ITD positive leukemia initially responded to Pexidartinib (PLX3397), but experienced relapse after emergence of a compound FLT3 M837G/S838R/D839H mutation on the FLT3-ITD allele (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D835G Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D835G were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D835G hematologic cancer sensitive HQP1351 Preclinical - Cell culture Actionable In a preclinical study, GZD824 (HQP1351) inhibited growth of transformed cells expressing FLT3-ITD and FLT3 D835G in culture (PMID: 32247263). 32247263
FLT3 exon 14 ins FLT3 F691L FLT3 D835G Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/D835G mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D698N Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D698N were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D698N Advanced Solid Tumor resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing FLT3 ITD and FLT3 D698N were resistant to treatment with Xospata (gilteritinib) in culture (Blood (2019) 134 (Supplement_1): 2672). detail...
FLT3 exon 14 ins FLT3 F691L FLT3 D698N Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/D698N mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D839A Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D839A were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L FLT3 D839A Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/D835A mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D839N Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D839N were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L FLT3 D839N Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/D839N were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 G846R Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD with FLT3 G846R were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L FLT3 G846R Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691Q/G846R mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 M664I Advanced Solid Tumor decreased response Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD with FLT3 M664I displayed reduced sensitivity to PLX3397 relative to cells expressing FLT3-ITD in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 M664I FLT3 F691L Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/M664I mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 N676S Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD with FLT3 N676S were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 N676S myeloid leukemia resistant A-419259 Preclinical - Cell culture Actionable In a preclinical study, transformed myeloid leukemia cells co-expressing FLT-ITD and FLT3 N676S demonstrated resistance to A-419259 treatment in culture (PMID: 31790499). 31790499
FLT3 exon 14 ins FLT3 N676S FLT3 F691L Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/N676S mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 N841K Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 N841K were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L FLT3 N841K Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/N841K mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 R845G Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD with FLT3 R845G were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L FLT3 R845G Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/R845G mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 Y842S Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD with FLT3 Y842S were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L FLT3 Y842S Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/Y842S mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L FLT3 D835Y Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/D835Y mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 S652G leukemia predicted - resistant Pexidartinib Case Reports/Case Series Actionable In a clinical case study, a patient with FLT3-ITD positive leukemia initially responded to Pexidartinib (PLX3397), but experienced relapse after emergence of a FLT3 S652G mutation on the same allele as FLT3-ITD (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 N676D FLT3 Y842C leukemia sensitive E6201 Preclinical Actionable In a preclinical study, E6201 inhibited proliferation and induced apoptosis in FLT3 inhibitor-resistant leukemia cell lines harboring FLT3 N676D and Y842C in addition to FLT3 internal tandem duplications (ITD) in culture (PMID: 26822154). 26822154
FLT3 exon 14 ins FLT3 D835X acute myeloid leukemia sensitive Crenolanib Phase I Actionable In a Phase I trial, Crenolanib treatment resulted in an overall survival (OS) of 128 days in AML patients harboring both FLT3 D835X and exon 14 insertion (ITD) that received no prior therapy, and an OS of 63 days in those progressed on TKIs (J Clin Oncol 34, 2016 (suppl; abstr 7008)). detail...
FLT3 exon 14 ins FLT3 D835X acute myeloid leukemia sensitive Selinexor + Sorafenib Phase Ib/II Actionable In a Phase I/II trial, combination of Selinexor and Nexavar (sorafenib) treatment resulted in complete remission in 29% (4/14) and more than 50% blast reduction in 14% (2/14) of patients with acute myeloid leukemia harboring FLT3 ITD and/or D835 mutations (ASH, 59th Annual Meeting and Exposition, Dec 2017, Abstract 1344; NCT01607892). detail...
FLT3 exon 14 ins FLT3 F691I Advanced Solid Tumor resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and F691I were resistant to Rydapt (midostaurin) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 F691I Advanced Solid Tumor resistant Sorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and F691I were resistant to Nexavar (sorafenib) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 F691I Advanced Solid Tumor resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and F691I were resistant to Quizartinib (AC220) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 F691I Advanced Solid Tumor decreased response Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3 ITD and F691I demonstrated reduced sensitivity to Alunbrig (brigatinib) compared to cells expressing FLT3 ITD in culture (PMID: 27780853). 27780853
FLT3 exon 14 ins FLT3 F691I Advanced Solid Tumor decreased response Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and F691I demonstrated reduced response to Sutent (sunitinib) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 F691I hematologic cancer sensitive HQP1351 Preclinical - Cell line xenograft Actionable In a preclinical study, GZD824 (HQP1351) reduced Flt3 and Stat5 phosphorylation and inhibited growth of transformed cells expressing FLT3-ITD and FLT3 F691I in culture, and suppressed tumor growth, decreased Flt3 activation, and induced apoptosis in cell line xenograft models (PMID: 32247263). 32247263
FLT3 exon 14 ins FLT3 N676D hematologic cancer sensitive SKI-G-801 Preclinical - Cell culture Actionable In a preclinical study, cells co-expressing a FLT3 internal tandem duplication and FLT3 N676D were sensitive to SKI-G-801 in culture, demonstrating inhibition of cell growth and inhibition of Flt3 autophosphorylation (PMID: 24532805). 24532805
FLT3 exon 14 ins FLT3 N676D Advanced Solid Tumor decreased response Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and N676D demonstrated reduced sensitivity to Quizartinib (AC220) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 N676D hematologic cancer sensitive LT-171-861 Preclinical - Cell line xenograft Actionable In a preclinical study, LT-171-861 inhibited cell viability and decreased FLT3 phosphorylation in transformed hematologic cells expressing a FLT3-ITD mutation and FLT3 N676D in culture, and inhibited tumor growth and prolonged survival in cell line xenograft models (PMID: 33391463). 33391463
FLT3 exon 14 ins FLT3 N676D Advanced Solid Tumor resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and N676D were resistant to Rydapt (midostaurin) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 N676D hematologic cancer sensitive HQP1351 Preclinical - Cell culture Actionable In a preclinical study, GZD824 (HQP1351) inhibited growth of transformed cells expressing FLT3-ITD and FLT3 N676D in culture (PMID: 32247263). 32247263
FLT3 exon 14 ins FLT3 A848P Advanced Solid Tumor decreased response Sorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and A848P demonstrated reduced sensitivity to Nexavar (sorafenib) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 A848P Advanced Solid Tumor resistant Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and A848P were resistant to Sutent (sunitinib) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 A848P Advanced Solid Tumor decreased response Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and A848P demonstrated reduced sensitivity to Quizartinib (AC220) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 F621L acute myeloid leukemia sensitive Sorafenib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication (ITD) and expressing FLT3 F621L demonstrated sensitivity to Nexavar (sorafenib) in culture (Blood 2009 114:3776). detail...
FLT3 exon 14 ins FLT3 F621L acute myeloid leukemia decreased response AGL2043 Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication (ITD) and expressing FLT3 F621L demonstrated a decreased response to AGL2043 in culture when compared to treated cells harboring a FLT3 ITD and expressing FLT3 Y842C (Blood 2009 114:3776). detail...
FLT3 exon 14 ins FLT3 F621L acute myeloid leukemia sensitive Lestaurtinib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication (ITD) and expressing FLT3 F621L demonstrated sensitivity to Lestaurtinib (CEP-701) in culture (Blood 2009 114:3776). detail...
FLT3 exon 14 ins FLT3 F621L hematologic cancer sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 F621L were sensitive to treatment with Vanflyta (Quizartinib), demonstrating growth inhibition in culture (PMID: 22858906). 22858906
FLT3 exon 14 ins FLT3 F621L acute myeloid leukemia sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication (ITD) and expressing FLT3 F621L demonstrated sensitivity to Rydapt (midostaurin) in culture (Blood 2009 114:3776). detail...
FLT3 exon 14 ins FLT3 F621L hematologic cancer resistant KW-2449 Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 F621L were resistant to treatment with KW-2449 in culture (PMID: 22858906). 22858906
FLT3 exon 14 ins FLT3 F621L acute myeloid leukemia decreased response Sunitinib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication (ITD) and expressing FLT3 F621L demonstrated a decreased response to Sutent (sunitinib) in culture when compared to treated cells harboring a FLT3 ITD and expressing FLT3 Y842C (Blood 2009 114:3776). detail...
FLT3 exon 14 ins FLT3 LOH acute myeloid leukemia sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Quizartinib (AC220) inhibited proliferation of a acute myeloid leukemia cell line harboring a FLT3-ITD mutation with FLT3 loss of heterozygosity (PMID: 28895560). 28895560
FLT3 exon 14 ins FLT3 LOH acute myeloid leukemia sensitive FLT3/CD3 Fabsc antibody + Quizartinib Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of Quizartinib (AC220) and an Fabsc FLT3/CD3 bi-specific antibody resulted in increased cytotoxicity over either agent alone in an acute myeloid leukemia cell line and patient-derived xenograft (PDX)-derived AML cells with a FLT3-ITD mutation and FLT3 loss of heterozygosity, leading to near complete eradication of AML cells in culture (PMID: 28895560). 28895560
FLT3 exon 14 ins FLT3 E654D acute myeloid leukemia predicted - sensitive HQP1351 Preclinical - Patient cell culture Actionable In a preclinical study, GZD824 (HQP1351) reduced Flt3 and Stat5 activation and inhibited growth of patient-derived acute myeloid leukemia cells harboring FLT3-ITD and FLT3 E654D in culture (PMID: 32247263). 32247263
FLT3 exon 14 ins FLT3 G697R hematologic cancer sensitive HQP1351 Preclinical - Cell culture Actionable In a preclinical study, GZD824 (HQP1351) inhibited growth of transformed cells expressing FLT3-ITD and FLT3 G697R in culture (PMID: 32247263). 32247263
FLT3 exon 14 ins FLT3 Y842R hematologic cancer sensitive HQP1351 Preclinical Actionable In a preclinical study, GZD824 (HQP1351) inhibited growth of transformed cells expressing FLT3-ITD and FLT3 Y842R in culture (PMID: 32247263). 32247263
FLT3 exon 14 ins FLT3 D835A hematologic cancer sensitive HQP1351 Preclinical - Cell culture Actionable In a preclinical study, GZD824 (HQP1351) inhibited growth of transformed cells expressing FLT3-ITD and FLT3 D835A in culture (PMID: 32247263). 32247263
FLT3 exon 14 ins FLT3 D835I hematologic cancer predicted - sensitive HQP1351 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 D835I demonstrated decreased proliferation in response to GZD824 (HQP1351) in culture, but were less sensitive to treatment than cells co-expressing FLT3-ITD with other FLT3 kinase domain mutations (PMID: 32247263). 32247263
FLT3 exon 14 ins FLT3 D835I acute myeloid leukemia predicted - resistant Sorafenib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835I demonstrated resistance to Nexavar (sorafenib) treatment in culture (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 D835I acute myeloid leukemia predicted - sensitive Gilteritinib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835I demonstrated sensitivity to Xospata (gilteritinib) treatment in culture, resulting in reduced cell viability and inhibition of Flt3 phosphorylation (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 D835I acute myeloid leukemia predicted - resistant Quizartinib Case Reports/Case Series Actionable In a clinical case study, FLT3 D835I was identified as an acquired resistance mutation in a patient with acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD) whose disease progressed on Vanflyta (Quizartinib) after an initial response (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 A627P hematologic cancer resistant Sorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 A627P were resistant to treatment with Nexavar (sorafenib) in culture (PMID: 22858906). 22858906
FLT3 exon 14 ins FLT3 A627P hematologic cancer resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 A627P were resistant to treatment with Vanflyta (Quizartinib) in culture (PMID: 22858906). 22858906
FLT3 exon 14 ins FLT3 A627P hematologic cancer resistant Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 A627P were resistant to treatment with Sutent (sunitinib) in culture (PMID: 22858906). 22858906
FLT3 exon 14 ins FLT3 A627P hematologic cancer resistant Lestaurtinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 A627P were resistant to treatment with Lestaurtinib (CEP-701) in culture (PMID: 22858906). 22858906
FLT3 exon 14 ins FLT3 A627P hematologic cancer resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 A627P were resistant to treatment with Rydapt (midostaurin) in culture (PMID: 22858906). 22858906
FLT3 exon 14 ins FLT3 A627P hematologic cancer resistant KW-2449 Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 A627P were resistant to treatment with KW-2449 in culture (PMID: 22858906). 22858906
FLT3 exon 14 ins FLT3 N676T Advanced Solid Tumor resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing FLT3 ITD and FLT3 N676T were resistant to treatment with Rydapt (midostaurin) in culture (Blood (2019) 134 (Supplement_1): 2672). detail...
FLT3 exon 14 ins FLT3 N676T Advanced Solid Tumor resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing FLT3 ITD and FLT3 N676T were resistant to treatment with Vanflyta (quizartinib) in culture (Blood (2019) 134 (Supplement_1): 2672). detail...
FLT3 exon 14 ins FLT3 F691L FLT3 D835I acute myeloid leukemia predicted - resistant Crenolanib Case Reports/Case Series Actionable In a clinical case study, FLT3 F691L was identified as an acquired resistance mutation in a patient with acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835I whose disease progressed following Crenolanib (CP-868596) treatment (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 F691L FLT3 D835I acute myeloid leukemia predicted - resistant Crenolanib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) with FLT3 F691L and FLT3 D835I demonstrated resistance to Crenolanib (CP-868596) treatment in culture (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 F691L FLT3 D835I acute myeloid leukemia predicted - resistant Gilteritinib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) with FLT3 F691L and FLT3 D835I demonstrated resistance to Xospata (gilteritinib) treatment in culture (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 F691L FLT3 D835I acute myeloid leukemia predicted - resistant Quizartinib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) with FLT3 F691L and FLT3 D835I demonstrated resistance to Vanflyta (Quizartinib) treatment in culture (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 F691L FLT3 D835I acute myeloid leukemia predicted - resistant Midostaurin Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) with FLT3 F691L and FLT3 D835I demonstrated resistance to Rydapt (midostaurin) treatment in culture (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 F691L FLT3 D835I acute myeloid leukemia predicted - resistant Sorafenib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) with FLT3 F691L and FLT3 D835I demonstrated resistance to Nexavar (sorafenib) treatment in culture (PMID: 27908881). 27908881
FLT3 exon 14 ins NRAS G12D acute myeloid leukemia predicted - resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) failed to inhibit growth of acute myeloid leukemia cells harboring a FLT3-ITD mutation and NRAS G12D in culture (PMID: 33268594). 33268594
FLT3 exon 14 ins NRAS G12D acute myeloid leukemia predicted - sensitive Dubermatinib Preclinical - Cell culture Actionable In a preclinical study, Dubermatinib (TP-0903) inhibited growth of acute myeloid leukemia cells harboring a FLT3-ITD mutation and NRAS G12D in culture (PMID: 33268594). 33268594
FLT3 exon 14 ins IDH2 R140Q acute myeloid leukemia predicted - sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, high dosage Xospata (gilteritinib) treatment resulted in reduced viability and colony formation of cells isolated from a transgenic mouse model of acute myeloid leukemia harboring a FLT3-ITD mutation and IDH2 R140Q in culture (PMID: 33268594). 33268594
FLT3 exon 14 ins IDH2 R140Q acute myeloid leukemia predicted - resistant Midostaurin Preclinical Actionable In a preclinical study, Rydapt (midostaurin) failed to inhibit growth of cells isolated from a transgenic mouse model of acute myeloid leukemia harboring a FLT3-ITD mutation and IDH2 R140Q in culture (PMID: 33268594). 33268594
FLT3 exon 14 ins IDH2 R140Q acute myeloid leukemia predicted - resistant Quizartinib Preclinical Actionable In a preclinical study, Vanflyta (Quizartinib) failed to inhibit growth of cells isolated from a transgenic mouse model of acute myeloid leukemia harboring a FLT3-ITD mutation and IDH2 R140Q in culture (PMID: 33268594). 33268594
FLT3 exon 14 ins IDH2 R140Q acute myeloid leukemia predicted - sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, high dosage Crenolanib (CP-868596) treatment resulted in reduced viability of cells isolated from a transgenic mouse model of acute myeloid leukemia harboring a FLT3-ITD mutation and IDH2 R140Q in culture (PMID: 33268594). 33268594
FLT3 exon 14 ins IDH2 R140Q acute myeloid leukemia predicted - sensitive Dubermatinib Preclinical Actionable In a preclinical study, Dubermatinib (TP-0903) treatment inhibited growth and colony formation of cells isolated from a transgenic mouse model of acute myeloid leukemia harboring a FLT3-ITD mutation and IDH2 R140Q in culture, and increased survival in mouse models (PMID: 33268594). 33268594
FLT3 exon 14 ins IDH2 R140Q acute myeloid leukemia predicted - resistant Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) failed to inhibit growth of cells isolated from a transgenic mouse model of acute myeloid leukemia harboring a FLT3-ITD mutation and IDH2 R140Q in culture (PMID: 33268594). 33268594
FLT3 exon 14 ins JAK2 V617F hematologic cancer resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK2 V617F were resistant to treatment with Xospata (gilteritinib) in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK2 V617F hematologic cancer resistant Ruxolitinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK2 V617F were resistant to treatment with Jakafi (ruxolitinib) in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK2 V617F hematologic cancer resistant Tofacitinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK2 V617F were resistant to treatment with Xeljanz (tofacitinib) in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK2 V617F hematologic cancer decreased response Midostaurin + Tofacitinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK2 V617F demonstrated a decreased response to treatment with the combination of Rydapt (midostaurin) and Xeljanz (tofacitinib) compared to cells expressing a FLT3-ITD mutation and activating mutations of JAK1 or JAK3 in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK2 V617F hematologic cancer resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK2 V617F were resistant to treatment with Rydapt (midostaurin) in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK2 V617F hematologic cancer predicted - sensitive Pacritinib Preclinical - Cell culture Actionable In a preclinical study, Pacritinib (SB1518) treatment decreased cell proliferation and downstream signaling in transformed hematologic cells expressing a FLT3-ITD mutation and JAK2 V617F in culture but may not be capable of fully inhibiting Flt3 and Jak signaling at clinically achievable concentrations (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK2 V617F hematologic cancer sensitive Midostaurin + Ruxolitinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Rydapt (midostaurin) and Jakafi (ruxolitinib) inhibited cell growth and downstream signaling of transformed hematologic cells expressing a FLT3-ITD mutation and JAK2 V617F in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK2 V617F hematologic cancer sensitive Gilteritinib + Ruxolitinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Xospata (gilteritinib) and Jakafi (ruxolitinib) inhibited growth of transformed hematologic cells expressing a FLT3-ITD mutation and JAK2 V617F in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 V722I hematologic cancer resistant Tofacitinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I were resistant to treatment with Xeljanz (tofacitinib) in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 V722I hematologic cancer sensitive Midostaurin + Tofacitinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Rydapt (midostaurin) and Xeljanz (tofacitinib) inhibited cell growth and downstream signaling of transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 V722I acute myeloid leukemia predicted - resistant Sorafenib Case Reports/Case Series Actionable In a clinical case study, a patient with acute myeloid leukemia harboring a FLT3-ITD mutation treated with Nexavar (sorafenib) was found to have acquired a JAK3 V722I mutation with a variant allele frequency of 49% upon relapse (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 V722I hematologic cancer resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I were resistant to treatment with Xospata (gilteritinib) in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 V722I hematologic cancer resistant Ruxolitinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I were resistant to treatment with Jakafi (ruxolitinib) in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 V722I hematologic cancer resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I were resistant to treatment with Rydapt (midostaurin) in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 V722I hematologic cancer sensitive Midostaurin + Ruxolitinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Rydapt (midostaurin) and Jakafi (ruxolitinib) inhibited cell growth and downstream signaling of transformed hematologic cells expressing aa FLT3-ITD mutation and JAK3 V722I in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 V722I hematologic cancer sensitive Gilteritinib + Ruxolitinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Xospata (gilteritinib) and Jakafi (ruxolitinib) inhibited growth of transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 V722I hematologic cancer decreased response Pacritinib Preclinical - Cell culture Actionable In a preclinical study, Pacritinib (SB1518) treatment decreased cell proliferation and Akt and Erk phosphorylation, but did not fully inhibit Stat5 phosphorylation in transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I and was less effective compared to treatment with the combination of a FLT3 inhibitor and a JAK inhibitor in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 R953* acute myeloid leukemia predicted - resistant Quizartinib Case Reports/Case Series Actionable In a clinical case study, a patient with acute myeloid leukemia harboring a FLT3-ITD mutation treated with Vanflyta (Quizartinib) was found to have acquired a JAK3 R953* mutation upon relapse (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 R953* hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited growth of transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 R953* in culture (PMID: 33149267). 33149267
KMT2A - AFF1 FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive CYC065 Preclinical - Cell culture Actionable In a preclinical study, an acute myeloid leukemia cell line harboring KMT2A-AFF1 and a FLT3-ITD was sensitive to treatment with CYC065 (Fadraciclib) in culture, demonstrating decreased cell viability (PMID: 32645016). 32645016
KMT2A - MLLT3 FLT3 exon 14 ins acute myeloid leukemia sensitive CYC065 Preclinical - Cell culture Actionable In a preclinical study, an acute myeloid leukemia cell line harboring a FLT3-ITD and KMT2A-MLLT3 was sensitive to treatment with CYC065 (Fadraciclib) in culture, demonstrating reduced cell viability, increased PARP cleavage, and decreased Mcl1 protein levels (PMID: 32645016). 32645016
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FLT3 exon14 acute myeloid leukemia sensitive Gilteritinib Guideline Actionable Xospata (gilteritinib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org). detail...
FLT3 exon14 acute myeloid leukemia sensitive Cytarabine + Daunorubicin + Midostaurin Guideline Actionable Rydapt (midostaurin), in combination with Cerubidine (daunorubicin) and Cytosar-U (cytarabine), is included in guidelines for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org). detail...
FLT3 mutant acute myeloid leukemia sensitive Zotiraciclib Preclinical - Cell line xenograft Actionable In a preclinical study, Zotiraciclib (TG02) inhibited growth of FLT3-mutated acute myeloid leukemia cells in culture, resulted in complete tumor regression in cell line xenograft animal models (PMID: 21860433). 21860433
FLT3 mutant acute myeloid leukemia sensitive Cytarabine + Venetoclax Guideline Actionable Venclexta (venetoclax) in combination with Cytosar-U (cytarabine) is included in guidelines for adult patients with acute myeloid leukemia harboring a FLT3 mutation (NCCN.org). detail...
FLT3 mutant acute myeloid leukemia sensitive Cytarabine + Venetoclax Phase Ib/II Actionable In a Phase I/II trial, Venclexta (venetoclax) in combination with low-dose cytarabine resulted in complete remission or complete remission with incomplete count recovery in 44% (7/16) of patients with acute myeloid leukemia harboring FLT3 mutations who were ineligible for intensive chemotherapy (ASH Annual Meeting, Dec 2018, Abstract 284; NCT02287233). detail...
FLT3 mutant acute myeloid leukemia sensitive Azacitidine + Midostaurin Phase Ib/II Actionable In a Phase Ib/II trial, acute myeloid leukemia patients harboring a FLT3 mutation demonstrated an improved remission duration when treated with the combination therapy, Rydapt (midostaurin) and Vidaza (azacitidine) (PMID: 25530214). 25530214
FLT3 mutant acute myeloid leukemia sensitive Decitabine + Venetoclax Guideline Actionable Venclexta (venetoclax) in combination with Dacogen (decitabine) is included in guidelines for adult patients with acute myeloid leukemia harboring a FLT3 mutation (NCCN.org). detail...
FLT3 mutant acute myeloid leukemia sensitive Crenolanib Phase I Actionable In a Phase I trial, Crenolanib treatment resulted in complete response (CR) in 39% (7/18), partial response (PR) in 11% (2/18), and an overall survival (OS) of 234 days in AML patients harboring FLT3 mutations (D835X, ITD, or both) that received no prior therapy, and CR in 17% (6/36), PR in 14% (5/36), and OS of 94 days in those progressed on TKIs (J Clin Oncol 34, 2016 (suppl; abstr 7008)). detail...
FLT3 mutant acute myeloid leukemia sensitive UNC2025 Preclinical Actionable In a preclinical study, UNC2025 inhibited FLT3 activation and growth of acute myeloid leukemia cells harboring a FLT3-ITD mutation in culture (PMID: 25068800). 25068800
FLT3 mutant acute myeloid leukemia sensitive Gilteritinib FDA approved - Has Companion Diagnostic Actionable In a Phase III trial (ADMIRAL) that supported FDA approval, Xospata (gilteritinib) treatment resulted in complete remission (CR) or CR with partial hematologic recovery in 21% (29/138) of patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD), D835, or I836 mutation (FDA.gov; NCT02421939). detail... detail...
FLT3 mutant acute myeloid leukemia sensitive Gilteritinib Phase Ib/II Actionable In a Phase I/II trial, treatment with Gilteritinib (ASP2215) resulted in an overall response rate of 49% (93/191) in patients with relapsed or refractory acute myeloid leukemia harboring FLT3 mutations, compared to 12% (7/58) in patients with wild-type FLT3 (PMID: 28645776; NCT02014558). detail... 28645776
FLT3 mutant acute myeloid leukemia sensitive Selinexor + Sorafenib Phase Ib/II Actionable In a Phase I/II trial, combination of Selinexor and Nexavar (sorafenib) treatment resulted in complete remission in 29% (4/14) and more than 50% blast reduction in 14% (2/14) of patients with acute myeloid leukemia harboring FLT3 ITD and/or D835 mutations (ASH, 59th Annual Meeting and Exposition, Dec 2017, Abstract 1344; NCT01607892). detail...
FLT3 mutant acute myeloid leukemia sensitive E6201 Preclinical Actionable In a preclinical study, acute myeloid leukemia cell lines harboring FLT3 mutations demonstrated increased sensitivity to E6201 induced growth inhibition and apoptosis in culture compared to FLT3 wild-type cells (PMID: 26822154). 26822154
FLT3 mutant acute myeloid leukemia sensitive Azacitidine + Venetoclax Guideline Actionable Venclexta (venetoclax) in combination with Vidaza (azacitidine) is included in guidelines for adult patients with acute myeloid leukemia harboring a FLT3 mutation (NCCN.org). detail...
FLT3 mutant acute myeloid leukemia sensitive Cytarabine + Daunorubicin + Midostaurin FDA approved - Has Companion Diagnostic Actionable In a Phase III trial that supported FDA approval, treatment with Rydapt (midostaurin), combined with Cytosar-U (cytarabine) and Daunorubicin, improved overall survival (HR=0.78, p=0.009) and event-free survival (HR=0.78, p=0.002) in patients with FLT3-mutant (ITD, D835X, and I836X mutations) acute myeloid leukemia compared to Cytosar-U (cytarabine) and Daunorubicin with placebo (PMID: 28644114; NCT00651261). 28644114 detail... detail...
FLT3 mutant acute myeloid leukemia sensitive Cytarabine + Daunorubicin + Midostaurin Phase Ib/II Actionable In a Phase Ib clinical trial, Rydapt (midostaurin) treatment after Daunorubicin and Cytosar-U (cytarabine) induction resulted in complete remission in 92% (12/13) of acute myeloid leukemia patients carrying FLT3 mutations, although overall survival rate was similar to patients with wild-type FLT3 (PMID: 22627678). 22627678
FLT3 act mut acute myeloid leukemia sensitive Crenolanib Phase II Actionable In a Phase II trial, relapsed or refractory acute myeloid leukemia patients harboring FLT3 activating mutations without a history of FLT3 therapy demonstrated a significantly greater overall survival and event free survival compared to those that had prior FLT3 therapy when treated with Crenolanib (ASH meeting, Dec 2014, abstract #389). detail...
FLT3 act mut acute myeloid leukemia sensitive Palbociclib + SGI-1776 Preclinical Actionable In a preclinical study, Ibrance (palbociclib) and SGI-1776 were synergistic towards growth inhibition of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147). 27099147
FLT3 act mut acute myeloid leukemia sensitive Cytarabine + Daunorubicin + Sunitinib Phase Ib/II Actionable In a Phase Ib/II trial, 59% (13/22) of acute myeloid leukemia patients harboring FLT3 activating mutations achieved complete remission following treatment with Sutent (sunitinib) in combination with Cytarabine and Daunorubicin (PMID: 25818407). 25818407
FLT3 act mut acute myeloid leukemia sensitive Palbociclib + Tandutinib Preclinical Actionable In a preclinical study, Ibrance (palbociclib) and tandutinib (MLN518) were synergistic towards growth inhibition of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147). 27099147
FLT3 act mut leukemia sensitive Pexidartinib Preclinical - Cell line xenograft Actionable In a preclinical study, PLX3397 inhibited FLT3 autophosphorylation in leukemia cells overexpressing FLT3 or harboring FLT3 activating mutations, and inhibited growth of leukemia cells harboring FLT3-ITD mutations in culture and in cell line xenograft models (ASH Annual Meeting Abstracts 2011 118: 3632). detail...
FLT3 act mut acute myeloid leukemia sensitive Palbociclib Preclinical Actionable In a preclinical study, Ibrance (palbociclib) blocked growth, induced apoptosis, and inhibited STAT activation in human FLT3-ITD positive human acute myeloid leukemia cells in culture (PMID: 27099147). 27099147
FLT3 act mut acute myeloid leukemia sensitive TCS 359 Preclinical Actionable In a preclinical study, TCS-359 inhibited growth of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147). 27099147
FLT3 act mut acute myeloid leukemia sensitive VS-5584 Preclinical - Cell line xenograft Actionable In a preclinical study, VS-5584 inhibited PI3K/mTOR signaling and cell proliferation in a FLT3-ITD positive human acute myeloid leukemia cell line in culture, and inhibited tumor growth in xenograft models (PMID: 23270925). 23270925
FLT3 act mut acute myeloid leukemia sensitive Palbociclib + TCS 359 Preclinical Actionable In a preclinical study, Ibrance (palbociclib) following TCS-359 treatment enhanced growth inhibition of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147). 27099147
FLT3 act mut acute myeloid leukemia sensitive Palbociclib + Quizartinib Preclinical Actionable In a preclinical study, Ibrance (palbociclib) and Quizartinib (AC220) were synergistic towards growth inhibition of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147). 27099147
Molecular Profile Protein Effect Treatment Approaches
FLT3 exon 14 ins gain of function - predicted FLT3 Inhibitor
FLT3 exon 14 ins FLT3 F691L
FLT3 exon 14 ins FLT3 D835Y
FLT3 exon 14 ins FLT3 D835V
FLT3 exon 14 ins FLT3 D835F
FLT3 exon 14 ins FLT3 Y842H
FLT3 exon 14 ins FLT3 Y842C
FLT3 exon 14 ins FLT3 R834Q
FLT3 exon 14 ins FLT3 F691L FLT3 R834Q
FLT3 exon 14 ins FLT3 D835E
FLT3 exon 14 ins FLT3 F691L FLT3 D835E
FLT3 exon 14 ins FLT3 D835H
FLT3 exon 14 ins FLT3 F691L FLT3 D835H
FLT3 exon 14 ins FLT3 D835N
FLT3 exon 14 ins FLT3 F691L FLT3 D835N
FLT3 exon 14 ins FLT3 F691L FLT3 D839G
FLT3 exon 14 ins FLT3 D839G
FLT3 exon 14 ins FLT3 D839H
FLT3 exon 14 ins FLT3 F691L FLT3 Y842C
FLT3 exon 14 ins FLT3 F691L FLT3 Y842H
FLT3 exon 14 ins FLT3 M837G FLT3 S838R FLT3 D839H
FLT3 exon 14 ins FLT3 D835G
FLT3 exon 14 ins FLT3 F691L FLT3 D835G
FLT3 exon 14 ins FLT3 D698N
FLT3 exon 14 ins FLT3 F691L FLT3 D698N
FLT3 exon 14 ins FLT3 D839A
FLT3 exon 14 ins FLT3 F691L FLT3 D839A
FLT3 exon 14 ins FLT3 D839N
FLT3 exon 14 ins FLT3 F691L FLT3 D839N
FLT3 exon 14 ins FLT3 G846R
FLT3 exon 14 ins FLT3 F691L FLT3 G846R
FLT3 exon 14 ins FLT3 M664I
FLT3 exon 14 ins FLT3 M664I FLT3 F691L
FLT3 exon 14 ins FLT3 N676S
FLT3 exon 14 ins FLT3 N676S FLT3 F691L
FLT3 exon 14 ins FLT3 N841K
FLT3 exon 14 ins FLT3 F691L FLT3 N841K
FLT3 exon 14 ins FLT3 R845G
FLT3 exon 14 ins FLT3 F691L FLT3 R845G
FLT3 exon 14 ins FLT3 T820A
FLT3 exon 14 ins FLT3 Y842S
FLT3 exon 14 ins FLT3 F691L FLT3 Y842S
FLT3 exon 14 ins FLT3 F691L FLT3 D835Y
FLT3 exon 14 ins FLT3 S652G
FLT3 exon 14 ins FLT3 N676D FLT3 Y842C
FLT3 exon 14 ins FLT3 D835X
FLT3 exon 14 ins FLT3 F691I
FLT3 exon 14 ins FLT3 N676D
FLT3 exon 14 ins FLT3 A848P
FLT3 exon 14 ins FLT3 F621L
FLT3 exon 14 ins FLT3 LOH
FLT3 exon 14 ins FLT3 E654D
FLT3 exon 14 ins FLT3 G697R
FLT3 exon 14 ins FLT3 Y842R
FLT3 exon 14 ins FLT3 D835A
FLT3 exon 14 ins FLT3 D835I
FLT3 exon 14 ins FLT3 A627P
FLT3 exon 14 ins FLT3 N676T
FLT3 exon 14 ins FLT3 F691L FLT3 D835I
FLT3 exon 14 ins NRAS G12D
FLT3 exon 14 ins IDH2 R140Q
FLT3 exon 14 ins JAK2 V617F
FLT3 exon 14 ins JAK3 V722I
FLT3 exon 14 ins JAK3 R953*
KMT2A - AFF1 FLT3 exon 14 ins
KMT2A - MLLT3 FLT3 exon 14 ins