Molecular Profile Detail

Profile Name FLT3 S451F
Gene Variant Detail

FLT3 S451F (gain of function)

Relevant Treatment Approaches FLT3 Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
FLT3 exon 14 ins FLT3 R845G Advanced Solid Tumor resistant FLT3 Inhibitor 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 FLT3 Inhibitor 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 Y599_D600insGLYVDFREYEY acute myeloid leukemia sensitive FLT3 Inhibitor Tandutinib Preclinical Actionable In a preclinical study, tandutinib (CT53518) inhibited proliferation of cells expressing FLT3 Y599_D600insGLYVDFREYEY in culture (PMID: 12124172). 12124172
FLT3 exon 14 ins FLT3 F691L FLT3 Y842S Advanced Solid Tumor resistant FLT3 Inhibitor 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 D835Y FLT3 F691L hematologic cancer resistant FLT3 Inhibitor Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib did not decrease cell proliferation of transformed mouse cells expressing Flt3 D835Y and Flt3 F691L, indicating F691L as a resistance mutation since D835Y was sensitive alone (PMID: 30651561). 30651561
FLT3 exon 14 ins FLT3 F691L FLT3 Y842C Advanced Solid Tumor resistant FLT3 Inhibitor 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 N676S FLT3 F691L Advanced Solid Tumor resistant FLT3 Inhibitor 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 F691L acute myeloid leukemia sensitive FLT3 Inhibitor 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 leukemia sensitive FLT3 Inhibitor 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 sensitive FLT3 Inhibitor 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 Advanced Solid Tumor resistant FLT3 Inhibitor 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 leukemia predicted - sensitive FLT3 Inhibitor 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 resistant FLT3 Inhibitor 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 Advanced Solid Tumor sensitive FLT3 Inhibitor 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 acute myeloid leukemia decreased response FLT3 Inhibitor 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 FLT3 Inhibitor G-749 Preclinical - Cell culture Actionable In a preclinical study, cells co-expressing a FLT3 internal tandem duplication and FLT3 F691L were sensitive to G-749 in culture, demonstrating inhibition of cell growth and inhibition of Flt3 autophosphorylation (PMID: 22864397). 22864397
FLT3 exon 14 ins FLT3 F691L leukemia sensitive FLT3 Inhibitor 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 Advanced Solid Tumor sensitive FLT3 Inhibitor 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 Advanced Solid Tumor sensitive FLT3 Inhibitor 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 acute myeloid leukemia decreased response FLT3 Inhibitor 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 FLT3 D835G Advanced Solid Tumor resistant FLT3 Inhibitor 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 F691L FLT3 D698N Advanced Solid Tumor resistant FLT3 Inhibitor 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 F691L FLT3 D839N Advanced Solid Tumor resistant FLT3 Inhibitor 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 F691L FLT3 D835N Advanced Solid Tumor resistant FLT3 Inhibitor 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 Y842H Advanced Solid Tumor resistant FLT3 Inhibitor 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 F691L FLT3 R834Q Advanced Solid Tumor resistant FLT3 Inhibitor 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 F691L FLT3 D839G Advanced Solid Tumor resistant FLT3 Inhibitor 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 F691L FLT3 D835Y Advanced Solid Tumor resistant FLT3 Inhibitor 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 F691L FLT3 D839A Advanced Solid Tumor resistant FLT3 Inhibitor 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 M664I FLT3 F691L Advanced Solid Tumor resistant FLT3 Inhibitor 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 F691L FLT3 D835H Advanced Solid Tumor resistant FLT3 Inhibitor 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 F691L FLT3 D835E Advanced Solid Tumor resistant FLT3 Inhibitor 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 F691L FLT3 N841K Advanced Solid Tumor resistant FLT3 Inhibitor 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 F691L FLT3 G846R Advanced Solid Tumor resistant FLT3 Inhibitor 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 FLT3 Inhibitor 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 L611_E612insCSSDNEYFYVDFREYEYDLKWEFPRENL acute myeloid leukemia sensitive FLT3 Inhibitor Tandutinib Preclinical Actionable In a preclinical study, tandutinib (CT53518) inhibited proliferation of cells expressing FLT3 L611_E612insCSSDNEYFYVDFREYEYDLKWEFPRENL in culture (PMID: 12124172). 12124172
FLT3 act mut acute myeloid leukemia sensitive FLT3 Inhibitor 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
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 FLT3 Inhibitor 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 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 FLT3 Inhibitor 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 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 FLT3 Inhibitor 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 FLT3 Inhibitor Gilteritinib FDA approved 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...
FLT3 act mut acute myeloid leukemia sensitive FLT3 Inhibitor 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 leukemia sensitive FLT3 Inhibitor 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 FLT3 Inhibitor 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 exon 14 ins FLT3 S652G leukemia predicted - resistant FLT3 Inhibitor 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 D835V Advanced Solid Tumor resistant FLT3 Inhibitor 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 FLT3 Inhibitor 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 D835V Advanced Solid Tumor sensitive FLT3 Inhibitor 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 FLT3 D835V in culture (PMID: 27158668). 27158668
FLT3 D835V Advanced Solid Tumor resistant FLT3 Inhibitor Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3 D835V were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 I836del cancer sensitive FLT3 Inhibitor Tandutinib Preclinical - Cell culture Actionable In a preclinical study, Tandutinib (CT53518) inhibited phosphorylation of FLT3 and activation of ERK and STAT5, and reduced growth of transformed cells expressing FLT3 I836del in culture (PMID: 15256420). 15256420
FLT3 I836del cancer sensitive FLT3 Inhibitor Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited phosphorylation of FLT3, ERK, and STAT5, and growth of transformed cells expressing FLT3 I836del in culture (PMID: 17827387). 17827387
FLT3 D835X FLT3 exon 14 ins acute myeloid leukemia sensitive FLT3 Inhibitor 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 D835X FLT3 exon 14 ins acute myeloid leukemia sensitive FLT3 Inhibitor 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 D835X acute myeloid leukemia sensitive FLT3 Inhibitor 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 D835X acute myeloid leukemia sensitive FLT3 Inhibitor Crenolanib Phase I Actionable In a Phase I trial, Crenolanib treatment resulted in an overall survival (OS) of 185 days in AML patients harboring FLT3 D835X that received no prior therapy (J Clin Oncol 34, 2016 (suppl; abstr 7008)). detail...
FLT3 exon 14 ins FLT3 G846R Advanced Solid Tumor resistant FLT3 Inhibitor 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 amp colorectal cancer predicted - sensitive FLT3 Inhibitor Sorafenib Case Reports/Case Series Actionable In a clinical case study, Nexavar (sorafenib) treatment targeting FLT3 amplification in a rectal adenocarcinoma patient who had progressed on all standard therapies resulted in rapid clinical improvement (PMID: 25848357). 25848357
FLT3 exon 14 ins FLT3 M837G FLT3 S838R FLT3 D839H leukemia predicted - resistant FLT3 Inhibitor 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 Y842C acute myeloid leukemia sensitive FLT3 Inhibitor Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) induced cell death and inhibited FLT3 activation and downstream STAT5 activation in primary acute myeloid leukemic blasts harboring FLT3 Y842C in culture (PMID: 15345593). 15345593
FLT3 Y842C acute myeloid leukemia resistant Imatinib Preclinical Actionable In a preclinical study, primary AML blasts expressing FLT3 Y842C were resistant to Gleevec (imatinib) as demonstrated by constitutively phosphorylated FLT3 and STAT-5 (PMID: 15345593). 15345593
FLT3 ITD FLT3 N676D FLT3 Y842C leukemia sensitive FLT3 Inhibitor 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 Y842C leukemia sensitive FLT3 Inhibitor 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 acute myeloid leukemia resistant FLT3 Inhibitor 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 sensitive FLT3 Inhibitor 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 Advanced Solid Tumor resistant FLT3 Inhibitor 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 Advanced Solid Tumor sensitive FLT3 Inhibitor 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 Y842C hematologic cancer sensitive FLT3 Inhibitor 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 acute myeloid leukemia resistant FLT3 Inhibitor 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 acute myeloid leukemia sensitive FLT3 Inhibitor 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 FLT3 Inhibitor 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 F691I Advanced Solid Tumor decreased response FLT3 Inhibitor 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 Advanced Solid Tumor resistant FLT3 Inhibitor 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 decreased response FLT3 Inhibitor 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 resistant FLT3 Inhibitor 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 resistant FLT3 Inhibitor 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 D835F Advanced Solid Tumor resistant FLT3 Inhibitor 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 - sensitive FLT3 Inhibitor 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 acute myeloid leukemia predicted - resistant FLT3 Inhibitor 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 Advanced Solid Tumor sensitive FLT3 Inhibitor 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 Y842S Advanced Solid Tumor resistant FLT3 Inhibitor 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 D835Y FLT3 D200N hematologic cancer sensitive FLT3 Inhibitor Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib decreased cell proliferation of transformed mouse cells expressing Flt3 D835Y and Flt3 D200N (PMID: 30651561). 30651561
FLT3 S451F Advanced Solid Tumor decreased response FLT3 Inhibitor Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3 S451F demonstrated decreased sensitivity to inhibition of FLT3 phosphorylation and growth by Rydapt (midostaurin) in culture, when compared to cells expressing other FLT3 activating mutations (PMID: 18068628). 18068628
FLT3 exon 14 ins FLT3 D839G Advanced Solid Tumor resistant FLT3 Inhibitor 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 K429E hematologic cancer resistant FLT3 Inhibitor Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib did not decrease cell proliferation of transformed mouse cells expressing Flt3 K429E (PMID: 30651561). 30651561
FLT3 wild-type acute myeloid leukemia sensitive FLT3 Inhibitor Palbociclib + TCS 359 Preclinical Actionable In a preclinical study, Ibrance (palbociclib) following TCS-359 treatment enhanced growth inhibition of FLT3 wild-type acute myeloid leukemia cell lines in culture (PMID: 27099147). 27099147
FLT3 wild-type Advanced Solid Tumor sensitive FLT3 Inhibitor Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited FLT3 phosphorylation in transformed cells expressing wild-type FLT3 in culture (PMID: 12124173). 12124173
FLT3 wild-type acute myeloid leukemia sensitive FLT3 Inhibitor 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 74% (20 of 27) of acute myeloid leukemia patients carrying wild-type FLT3 (PMID: 22627678). 22627678
FLT3 wild-type acute myeloid leukemia sensitive Palbociclib Preclinical Actionable In a preclinical study, Ibrance (palbociclib) inhibited growth of human FLT3 wild-type human leukemia cells in culture (PMID: 27099147). 27099147
FLT3 wild-type acute myeloid leukemia predicted - sensitive FLT3 Inhibitor CG-806 Preclinical - Cell culture Actionable In a preclinical study, CG'806 inhibited Btk and aurora kinase activation, induced G2/M arrest and autophagy in acute myeloid leukemia cells harboring wild-type FLT3 in culture (Blood 2017 130:4629). detail...
FLT3 wild-type acute myeloid leukemia sensitive FLT3 Inhibitor TCS 359 Preclinical Actionable In a preclinical study, TCS-359 inhibited growth of FLT3 wild-type acute myeloid leukemia cell lines in culture (PMID: 27099147). 27099147
FLT3 exon 14 ins FLT3 Y842H Advanced Solid Tumor resistant FLT3 Inhibitor 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 sensitive FLT3 Inhibitor 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 Advanced Solid Tumor decreased response FLT3 Inhibitor 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 hematologic cancer sensitive FLT3 Inhibitor 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 decreased response FLT3 Inhibitor 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 F621L acute myeloid leukemia sensitive FLT3 Inhibitor 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 acute myeloid leukemia sensitive FLT3 Inhibitor 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 acute myeloid leukemia sensitive FLT3 Inhibitor 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 FLT3 Inhibitor 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 decreased response FLT3 Inhibitor 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 N841K Advanced Solid Tumor resistant FLT3 Inhibitor 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 N676S Advanced Solid Tumor resistant FLT3 Inhibitor 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 D835E Advanced Solid Tumor resistant FLT3 Inhibitor 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 D839A Advanced Solid Tumor resistant FLT3 Inhibitor 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 D698N Advanced Solid Tumor resistant FLT3 Inhibitor 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 R834Q Advanced Solid Tumor resistant FLT3 Inhibitor Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD with FLT3 R834Q were resistant to PLX3397 in culture (PMID: 25847190). 25847190
DNMT3A mut FLT3 exon 14 ins NPM1 mut acute myeloid leukemia predicted - sensitive Entospletinib Preclinical - Patient cell culture Actionable In a preclinical study, co-occurrence of FLT3-ITD, DNMT3A, and NPM1 mutations correlated with sensitivity to Entospletinib in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). 30333627
DNMT3A mut FLT3 exon 14 ins NPM1 mut acute myeloid leukemia predicted - sensitive KO-539 Preclinical - Pdx Actionable In a preclinical study, KO-539 treatment resulted in clearance of leukemia cells in patient-derived xenograft (PDX) models of acute myeloid leukemia harboring mutations in NPM1, DNMT3, and FLT3 exon 14 (ITD) (AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr LB-A27). detail...
DNMT3A mut FLT3 exon 14 ins NPM1 mut acute myeloid leukemia predicted - sensitive Ibrutinib Preclinical - Patient cell culture Actionable In a preclinical study, co-occurrence of FLT3-ITD , DNMT3A, and NPM1 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 FLT3 D835N Advanced Solid Tumor resistant FLT3 Inhibitor 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 D835G Advanced Solid Tumor resistant FLT3 Inhibitor 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 acute myeloid leukemia predicted - sensitive FLT3 Inhibitor 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 FLT3 Inhibitor 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 acute myeloid leukemia sensitive FLT3 Inhibitor 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 FLT3 Inhibitor 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 leukemia sensitive FLT3 Inhibitor 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 FLT3 Inhibitor G-749 Preclinical - Cell line xenograft Actionable In a preclinical study, G-749 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 acute myeloid leukemia sensitive FLT3 Inhibitor 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 hematologic cancer sensitive FLT3 Inhibitor 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 FLT3 Inhibitor Cytarabine + Daunorubicin + Midostaurin Phase III 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 or FLT3-ITD acute myeloid leukemia compared to Cytosar-U (cytarabine) and Daunorubicin with placebo (PMID: 28644114). 28644114
FLT3 exon 14 ins leukemia predicted - sensitive FLT3 Inhibitor 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 FLT3 Inhibitor 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 FLT3 Inhibitor 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 no benefit FLT3 Inhibitor 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 FLT3 Inhibitor 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 FLT3 Inhibitor Cytarabine + G-749 Preclinical - Cell culture Actionable In a preclinical study, the combination of G-749 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 sensitive FLT3 Inhibitor 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 FLT3 Inhibitor 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 acute myeloid leukemia sensitive FLT3 Inhibitor 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 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 predicted - sensitive FLT3 Inhibitor 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 FLT3 Inhibitor 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 leukemia sensitive FLT3 Inhibitor 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 predicted - 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 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 Advanced Solid Tumor predicted - sensitive FLT3 Inhibitor 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 leukemia sensitive FLT3 Inhibitor 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 Advanced Solid Tumor sensitive FLT3 Inhibitor 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 predicted - sensitive FLT3 Inhibitor 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 FLT3 Inhibitor 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 predicted - sensitive FLT3 Inhibitor 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 FLT3 Inhibitor 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 acute myeloid leukemia sensitive FLT3 Inhibitor 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 FLT3 Inhibitor 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 FLT3 Inhibitor 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 predicted - sensitive FLT3 Inhibitor 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 FLT3 Inhibitor 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 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 acute myeloid leukemia predicted - sensitive FLT3 Inhibitor 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 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 Advanced Solid Tumor sensitive FLT3 Inhibitor 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 sensitive FLT3 Inhibitor 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 FLT3 Inhibitor 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 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 acute myeloid leukemia sensitive FLT3 Inhibitor 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 FLT3 D835Y leukemia predicted - resistant FLT3 Inhibitor 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 Advanced Solid Tumor sensitive FLT3 Inhibitor 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 Advanced Solid Tumor resistant FLT3 Inhibitor 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 leukemia predicted - sensitive FLT3 Inhibitor 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 Advanced Solid Tumor sensitive FLT3 Inhibitor 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 acute myeloid leukemia sensitive FLT3 Inhibitor 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 sensitive FLT3 Inhibitor 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 D839N Advanced Solid Tumor resistant FLT3 Inhibitor 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 D835H leukemia resistant FLT3 Inhibitor 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 acute myeloid leukemia sensitive FLT3 Inhibitor 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 D835H Advanced Solid Tumor resistant FLT3 Inhibitor 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 A848P Advanced Solid Tumor resistant FLT3 Inhibitor 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 FLT3 Inhibitor 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 A848P Advanced Solid Tumor decreased response FLT3 Inhibitor 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 N676D Advanced Solid Tumor decreased response FLT3 Inhibitor 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 FLT3 Inhibitor G-749 Preclinical - Cell culture Actionable In a preclinical study, cells co-expressing a FLT3 internal tandem duplication and FLT3 N676D were sensitive to G-749 in culture, demonstrating inhibition of cell growth and inhibition of Flt3 autophosphorylation (PMID: 22864397). 22864397
FLT3 exon 14 ins FLT3 N676D Advanced Solid Tumor resistant FLT3 Inhibitor 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 D839H Advanced Solid Tumor resistant FLT3 Inhibitor 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 NPM1 mutant leukemia predicted - sensitive EPZ004777 Preclinical Actionable In a preclinical study, EPZ004777 inhibited growth and induced differentiation of murine leukemia cells expressing an NPM1 mutation and FLT3 internal tandem duplication in culture, and improved survival in mouse models (PMID: 27535106). 27535106
FLT3 exon 14 ins NPM1 mutant acute myeloid leukemia predicted - sensitive FLT3 Inhibitor Sorafenib Preclinical - Patient cell culture Actionable In a preclinical study, co-occurrence of FLT3-ITD and NPM1 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 NPM1 mutant acute myeloid leukemia predicted - sensitive FLT3 Inhibitor Sunitinib Preclinical - Patient cell culture Actionable In a preclinical study, co-occurrence of FLT3-ITD and NPM1 mutations correlated with sensitivity to Sutent (sunitinib) in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). 30333627
FLT3 exon 14 ins NPM1 mutant acute myeloid leukemia sensitive FLT3 Inhibitor ENMD-2076 Phase I Actionable In a Phase I trial, two acute myeloid leukemia patients co-harboring a FLT3-ITD mutation and NPM1 mutation demonstrated anti-leukemia activity when treated with ENMD-2076 (PMID: 27406088). 27406088
FLT3 exon 14 ins NPM1 mutant acute myeloid leukemia predicted - sensitive Ibrutinib Preclinical - Patient cell culture Actionable In a preclinical study, co-occurrence of FLT3-ITD and NPM1 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 NPM1 mutant leukemia predicted - sensitive MI-503 Preclinical Actionable In a preclinical study, MI-503 inhibited growth of murine leukemia cells expressing an NPM1 mutation and FLT3 internal tandem duplication in culture, and improved survival in mouse models (PMID: 27535106). 27535106
FLT3 exon 14 ins NPM1 mutant acute myeloid leukemia predicted - sensitive Entospletinib Preclinical - Patient cell culture Actionable In a preclinical study, co-occurrence of FLT3-ITD and NPM1 mutations correlated with sensitivity to Entospletinib in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). 30333627
FLT3 V592G Advanced Solid Tumor sensitive FLT3 Inhibitor Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited FLT3-induced phosphorylation of ERK1/2 and reduced growth of transformed cells expressing FLT3 V592G in culture (PMID: 18068628). 18068628
FLT3 Y572C Advanced Solid Tumor sensitive FLT3 Inhibitor Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited FLT3 phosphorylation of ERK1/2 and reduced cell growth in transformed cells expressing FLT3 Y572C in culture (PMID: 18068628). 18068628
FLT3 Y572C hematologic cancer sensitive FLT3 Inhibitor Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib decreased cell proliferation of transformed mouse cells expressing Flt3 Y572C (PMID: 30651561). 30651561
FLT3 mutant acute myeloid leukemia sensitive FLT3 Inhibitor 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 FLT3 Inhibitor TG02 Preclinical - Cell line xenograft Actionable In a preclinical study, 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 predicted - sensitive FLT3 Inhibitor 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 FLT3 Inhibitor 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 FLT3 Inhibitor 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 FLT3 Inhibitor 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 FLT3 Inhibitor 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 mutant acute myeloid leukemia sensitive FLT3 Inhibitor Cytarabine + Daunorubicin + Midostaurin FDA approved 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 acute myeloid leukemia compared to Cytosar-U (cytarabine) and Daunorubicin with placebo (PMID: 28644114; NCT00651261). 28644114
FLT3 mutant acute myeloid leukemia predicted - 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 FLT3 Inhibitor 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...
DNMT3A wild-type FLT3 mut NPM1 mut acute myeloid leukemia predicted - sensitive KO-539 Preclinical - Pdx Actionable In a preclinical study, KO-539 treatment prevented disease progression in patient-derived xenograft (PDX) models of DNMT3A wild-type acute myeloid leukemia harboring mutations in NPM1 and FLT3 (AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr LB-A27). detail...
DNMT3A mut FLT3 mut NPM1 mut acute myeloid leukemia not applicable N/A Clinical Study Emerging In a retrospective analysis, the combination of DNMT3A, FLT3, and NPM1 mutations in patients with acute myeloid leukemia was highly associated with decreased event-free survival and overall survival, suggesting that this combination profile may serve as a future prognostic biomarker (PMID: 25281355). 25281355
FLT3 D835H acute myeloid leukemia sensitive FLT3 Inhibitor Crenolanib Preclinical Actionable In a preclinical study, Crenolanib (CP-868596) inhibited Flt3 phosphorylation and induced apoptosis in leukemia cells expressing FLT3 D835H (PMID: 24623852). 24623852
FLT3 D835Y FLT3 L601F hematologic cancer sensitive FLT3 Inhibitor Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib decreased cell proliferation of transformed mouse cells expressing Flt3 D835Y and Flt3 L601F (PMID: 30651561). 30651561
FLT3 E612_F613insGYVDFREYEYDLKWEFRPRENLEF acute myeloid leukemia sensitive FLT3 Inhibitor Tandutinib Preclinical Actionable In a preclinical study, tandutinib (CT53518) inhibited proliferation of cells expressing FLT3 E612_F613insGYVDFREYEYDLKWEFRPRENLEF in culture (PMID: 12124172). 12124172
FLT3 D835Y PTPN11 A72D hematologic cancer resistant FLT3 Inhibitor Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib, did not decrease cell proliferation of transformed mouse cells expressing Flt3 D835Y and Ptpn11 A72D, indicating Ptpn11 A72D as a resistance mutation since Flt3 D835Y was sensitive alone (PMID: 30651561). 30651561
FLT3 D835Y PTPN11 A72D hematologic cancer sensitive FLT3 Inhibitor Crenolanib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib, in combination with Mekinist (trametinib), synergistically decreased cell proliferation of transformed mouse cells expressing Flt3 D835Y and Ptpn11 A72D (PMID: 30651561). 30651561
FLT3 D835Y FLT3 N676D hematologic cancer sensitive FLT3 Inhibitor G-749 Preclinical - Cell culture Actionable In a preclinical study, cells co-expressing FLT3 D835Y and FLT3 N676D were sensitive to G-749 in culture, demonstrating inhibition of cell growth and inhibition of Flt3 autophosphorylation (PMID: 22864397). 22864397
FLT3 D835Y hematologic cancer sensitive FLT3 Inhibitor G-749 Preclinical - Cell culture Actionable In a preclinical study, cells expressing FLT3 D835Y were sensitive to G-749 in culture, demonstrating inhibition of cell growth and inhibition of Flt3 autophosphorylation (PMID: 22864397). 22864397
FLT3 D835Y hematologic cancer sensitive FLT3 Inhibitor Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib decreased cell proliferation of transformed mouse cells expressing Flt3 D835Y (PMID: 30651561). 30651561
FLT3 D835Y acute promyelocytic leukemia predicted - resistant Tretinoin Case Reports/Case Series Actionable In a clinical case study, a patient with acute promyelocytic leukemia developed meningeal relapse after maintenance therapy with Vesanoid (tretinoid), which was found to be due to a FLT3 D835Y variant (PMID: 27626069). 27626069
FLT3 D835Y leukemia predicted - sensitive FLT3 Inhibitor 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 D835Y in culture (Clin Cancer Res 2017; 23(24_Suppl):Abstract nr 25). detail...
FLT3 D835Y Advanced Solid Tumor resistant FLT3 Inhibitor Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3 D835Y were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 D835Y Advanced Solid Tumor sensitive FLT3 Inhibitor 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 FLT3 D835Y in culture (PMID: 27158668). 27158668
FLT3 D835Y Advanced Solid Tumor sensitive FLT3 Inhibitor Midostaurin Preclinical - Cell culture Actionable In a preclinical study, treatment with Rydapt (midostaurin) inhibited FLT3 phosphorylation and resulted in decreased proliferation and viability of transformed cells expressing FLT3 D835Y in culture (PMID: 12124173). 12124173
FLT3 D835Y leukemia sensitive FLT3 Inhibitor E6201 Preclinical Actionable In a preclinical study, E6201 inhibited proliferation and induced apoptosis in FLT3 inhibitor-resistant leukemia cell lines over expressing FLT3 D835Y in culture (PMID: 26822154). 26822154
FLT3 D835Y acute myeloid leukemia sensitive FLT3 Inhibitor E6201 Preclinical - Cell culture Actionable In a preclinical study, E6201 induced apoptosis in blast samples derived from acute myeloid leukemia patients harboring FLT3 D835Y in culture (PMID: 26822154). 26822154
FLT3 D835Y acute promyelocytic leukemia predicted - sensitive Arsenic trioxide + Cytarabine + Methotrexate + Tretinoin Case Reports/Case Series Actionable In a clinical case study, a patient with acute promyelocytic leukemia harboring FLT3 D835Y demonstrated a complete molecular remission after treatment with Trisenox (arsenic trioxide) and Vesanoid (tretinoin) combined with Cytosar-U (cytarabine) and Methotrexate (PMID: 27626069). 27626069
FLT3 D835Y hematologic cancer sensitive FLT3 Inhibitor Crenolanib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib, in combination with Mekinist (trametinib), synergistically decreased cell proliferation of transformed mouse cells expressing Flt3 D835Y (PMID: 30651561). 30651561
FLT3 D835Y IDH1 wild-type hematologic cancer resistant AGI-5198 Preclinical - Cell culture Actionable In a preclinical study, AGI-5198, did not decrease cell proliferation of transformed mouse cells expressing Flt3 D835Y and Idh1 wild-type (PMID: 30651561). 30651561
FLT3 D835Y IDH1 wild-type hematologic cancer sensitive FLT3 Inhibitor AGI-5198 + Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib, in combination with AGI-5198, synergistically decreased cell proliferation of transformed mouse cells expressing Flt3 D835Y and Idh1 wild-type (PMID: 30651561). 30651561
FLT3 D835Y IDH1 wild-type hematologic cancer sensitive FLT3 Inhibitor Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib, decreased cell proliferation of transformed mouse cells expressing Flt3 D835Y and Idh1 wild-type (PMID: 30651561). 30651561
FLT3 D835Y IDH1 R132H hematologic cancer resistant AGI-5198 Preclinical - Cell culture Actionable In a preclinical study, AGI-5198, did not decrease cell proliferation of transformed mouse cells expressing Flt3 D835Y and Idh1 R132H (PMID: 30651561). 30651561
FLT3 D835Y IDH1 R132H hematologic cancer sensitive FLT3 Inhibitor AGI-5198 + Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib, in combination with AGI-5198, synergistically decreased cell proliferation of transformed mouse cells expressing Flt3 D835Y and Idh1 R132H (PMID: 30651561). 30651561
FLT3 D835Y IDH1 R132H hematologic cancer sensitive FLT3 Inhibitor Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib, decreased cell proliferation of transformed mouse cells expressing Flt3 D835Y and Idh1 R132H (PMID: 30651561). 30651561
FLT3 E598_Y599insGLVQVTGSSDNEYFYVDFREYE acute myeloid leukemia sensitive FLT3 Inhibitor Tandutinib Preclinical Actionable In a preclinical study, tandutinib (CT53518) inhibited proliferation of cells expressing FLT3 E598_Y599insGLVQVTGSSDNEYFYVDFREYE in culture (PMID: 12124172). 12124172
FLT3 D835G leukemia sensitive FLT3 Inhibitor E6201 Preclinical Actionable In a preclinical study, E6201 inhibited proliferation and induced apoptosis in FLT3 inhibitor-resistant leukemia cell lines over expressing FLT3 D835G in culture (PMID: 26822154). 26822154
FLT3 D835G acute myeloid leukemia sensitive FLT3 Inhibitor E6201 Preclinical - Cell culture Actionable In a preclinical study, E6201 induced apoptosis in blast samples derived from acute myeloid leukemia patients harboring FLT3 D835G in culture (PMID: 26822154). 26822154
FLT3 positive acute myeloid leukemia not applicable AGS62P1 Preclinical - Patient cell culture Actionable In a preclinical study, AGS62P1 inhibited growth of FLT3-positive acute myeloid leukemia cell lines in culture, and led to tumor growth inhibition and regression in patient-derived xenograft (PDX) models (Blood 2015 126(23):3806). detail...
FLT3 Y599_D600insSTDNEYFYVDFREYEY acute myeloid leukemia predicted - sensitive FLT3 Inhibitor FLX925 Preclinical Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3-ITD secondary resistance mutation demonstrated sensitivity to FLX925 (Cancer Res, August 1, 2015 75; 787). detail...
FLT3 Y599_D600insSTDNEYFYVDFREYEY acute myeloid leukemia predicted - sensitive FLT3 Inhibitor E6201 Preclinical - Cell line xenograft Actionable In a preclinical study, E6201 induced cell death, inhibited cell growth, and decreased tumor burden in acute myeloid leukemia cells harboring FLT3-ITD mutations in culture and in cell line xenograft models (Blood Nov 2013, 122 (21) 2683). detail...
FLT3 Y599_D600insSTDNEYFYVDFREYEY acute myeloid leukemia predicted - sensitive FLT3 Inhibitor Azacitidine + Sorafenib Phase II Actionable In a Phase II trial, 93% (40/43) of acute myeloid leukemia patients harbored a FLT3-ITD and of the 37 patients that were evaluable, the combination therapy, Nexavar (sorafenib) and Vidaza (azacitidine), resulted in a 46% (17/37) response rate, which included 10 CRi, 6 CR, and 1 PR (PMID: 23613521). 23613521
FLT3 Y599_D600insSTDNEYFYVDFREYEY acute myeloid leukemia predicted - sensitive FLT3 Inhibitor Quizartinib Phase I Actionable In a Phase I clinical trial, patients with refractory or relapsed acute myeloid leukemia positive for FLT3-ITD demonstrated a 53% (9/17) response rate compared to a 14% (5/37) response rate in those patients negative for FLT3-ITD when treated with Quizartinib (AC220) (PMID: 24002496). 24002496
IDH2 R140W FLT3 Y599_D600insSTDNEYFYVDFREYEY acute myeloid leukemia predicted - sensitive FLT3 Inhibitor Enasidenib + Quizartinib Preclinical Actionable In a preclinical study, the combination of Enasidenib (AG-221) and Quizartinib (AC220) stimulated leukemic cell differentiation and reduced leukemic cell self-renewal in an acute myeloid leukemia mouse model simultaneously expressing IDH2 R140Q and a FLT3-ITD mutation (Blood Dec 2014, 124 (21) 437). detail...
FLT3 R595_L601dup acute myeloid leukemia sensitive FLT3 Inhibitor Tandutinib Preclinical Actionable In a preclinical study, tandutinib (CT53518) inhibited cell proliferation in cell culture and in mouse models carrying FLT3 L601_K602insREYEYDL (PMID: 12124172). 12124172
FLT3 R834Q Advanced Solid Tumor sensitive FLT3 Inhibitor Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited FLT3-induced phosphorylation of ERK1/2 and reduced growth of transformed cells expressing FLT3 R834Q in culture (PMID: 18068628). 18068628
FLT3 R834Q Advanced Solid Tumor sensitive PD98059 Preclinical Actionable In a preclinical study, PD98059 inhibited ERK1/2 phosphorylation and reduced cell growth in transformed cells expressing FLT3 R834Q (PMID: 18068628). 18068628
Clinical Trial Phase Therapies Title Recruitment Status