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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
Category Variants Paths

FLT3 mutant FLT3 exon14 FLT3 exon 14 ins

FLT3 mutant FLT3 act mut FLT3 exon 14 ins

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

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 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 acute myeloid leukemia predicted - sensitive Pacritinib Preclinical - Cell line xenograft Actionable In a preclinical study, Vonjo (pacritinib) 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 predicted - sensitive Pacritinib Preclinical - Cell culture Actionable In a preclinical study, Vonjo (pacritinib) inhibited viability in acute myeloid leukemia cell lines harboring a FLT3-ITD mutation in culture (PMID: 31102119). 31102119
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 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 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 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 Phase II Actionable In a Phase II trial, treatment with Crenolanib (CP-868596) and chemotherapy demonstrated efficacy in patients with newly diagnosed acute myeloid leukemia harboring FLT3-ITD and/or FLT3 tyrosine kinase domain (exons 14-23) mutations, with an overall response rate of 86% (38/86, 34 complete remission and 4 complete remission with incomplete recovery), median event-free survival of 44.7 months, and median overall survival that was not reached (PMID: 38324741; NCT02283177). 38324741
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 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 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 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 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 Vanflyta (quizartinib) 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 Phase II Actionable In a Phase II trial, Vanflyta (quizartinib) 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 FDA approved - On Companion Diagnostic Actionable In a Phase III trial (QuANTUM-First) that supported FDA approval, Vanflyta (quizartinib) in combination with induction and consolidation chemotherapy, followed by Vanflyta (quizartinib) maintenance improved median overall survival (31.9 vs 15.1 months, HR 0.78, p=0.032) compared to placebo in patients with newly-diagnosed acute myeloid leukemia harboring FLT3 internal tandem duplication (ITD; exon 14 insertion) (PMID: 37116523; NCT02668653). 37116523 detail...
FLT3 exon 14 ins acute myeloid leukemia sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Vanflyta (quizartinib) 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 Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Vanflyta (quizartinib) 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 Guideline Actionable Vanflyta (quizartinib) is included in guidelines as maintenance therapy for patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org). detail...
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 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 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 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 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 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 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 FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org). detail...
FLT3 exon 14 ins acute myeloid leukemia sensitive Cytarabine + Daunorubicin + Midostaurin Guideline Actionable Rydapt (midostaurin), in combination with Cerubidine (daunorubicin) and Cytosar-U (cytarabine), is included in guidelines as first-line treatment for patients with acute myeloid leukemia harboring FLT3 ITD mutations (PMID: 32171751; ESMO.org). 32171751 detail...
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) improved median overall survival (9.3 vs 5.6 mo, HR. 0.64, p<0.001), median event-free survival (2.8 vs 0.7 mo, HR 0.79), and rate of complete remission with full or partial hematologic recovery (34.0% vs 15.3%) compared to chemotherapy in patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD; exon 14 insertion), D835, or I836 mutation (PMID: 31665578; NCT02421939). detail... 31665578 detail...
FLT3 exon 14 ins acute myeloid leukemia sensitive Gilteritinib Phase III Actionable In a Phase III trial, post-hematopoietic cell transplantation maintenance Xospata (gilteritinib) treatment improved relapse-free survival in patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation who had detectable minimal residual disease pre- or post-hematopoietic cell transplantation compared to placebo, but was not beneficial in patients without minimal residual disease (PMID: 38471061; NCT02997202). 38471061
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 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 (PMID: 32171751; ESMO.org). detail... 32171751
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 acute myeloid leukemia predicted - sensitive Azacitidine + Quizartinib Phase Ib/II Actionable In a Phase I/II trial, Vanflyta (quizartinib) 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 predicted - sensitive Cytarabine + Quizartinib Phase Ib/II Actionable In a Phase I/II trial, Vanflyta (quizartinib) 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 predicted - sensitive Cytarabine + Quizartinib Guideline Actionable Vanflyta (quizartinib) in combination with Cytosar-U (cytarabine) is included in guidelines as consolidation therapy for patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org). detail...
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 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 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 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 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 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 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 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 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 acute myeloid leukemia sensitive Cytarabine + Daunorubicin + Quizartinib Phase I Actionable In a Phase I trial, the combination therapy, Vanflyta (quizartinib) 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 acute myeloid leukemia sensitive Cytarabine + Daunorubicin + Quizartinib Guideline Actionable Vanflyta (quizartinib) in combination with Cerubidine (daunorubicin) and Cytosar-U (cytarabine) is included in guidelines for patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org). detail...
FLT3 exon 14 ins acute myeloid leukemia sensitive CG-806 Preclinical - Cell line xenograft Actionable In a preclinical study, CG-806 inhibited downstream signaling, induced apoptosis, and inhibited proliferation of acute myeloid leukemia cell lines harboring a FLT3 exon 14 insertion (ITD) mutation in culture, and inhibited tumor growth in a cell line xenograft model (PMID: 35499387). 35499387
FLT3 exon 14 ins acute myeloid leukemia sensitive FF-10101 Phase I Actionable In a Phase I trial, FF-10101 treatment was well tolerated, and resulted in a composite complete remission (CRc) in 13% (4/30) and a partial remission (PR) in 13% (4/30) of patients with relapsed or refractory acute myeloid leukemia, 1 of the patients achieved CRc and 2 of the patients achieved PR harbored FLT3 ITD mutations (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 7008-7008; NCT03194685). detail...
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 sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of acute myeloid leukemia cells harboring FLT3-ITD in culture (PMID: 35395091). 35395091
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 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 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 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 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 Sorafenib Guideline Actionable Nexavar (sorafenib) is included in guidelines as maintenance therapy for patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org). detail...
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 a 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 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 Ibrutinib Preclinical - Cell culture Actionable In a preclinical study, Imbruvica (ibrutinib) treatment reduced viability of acute myeloid leukemia cells harboring FLT3-ITD mutations, however, with decreased response compared to cells treated with Abivertinib (AC0010) in culture (PMID: 31310800). 31310800
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 hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib (CP-868596) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD in culture (PMID: 35395091). 35395091
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 hematologic cancer sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Vanflyta (quizartinib) inhibited growth of transformed hematologic cells expressing FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). 31309543
FLT3 exon 14 ins hematologic cancer sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Vanflyta (quizartinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD in culture (PMID: 35395091). 35395091
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 hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD in culture (PMID: 35395091). 35395091
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 hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) treatment inhibited growth of transformed hematologic cells expressing a FLT3-ITD mutation in culture (PMID: 35395091). 35395091
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 Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Nexavar (sorafenib) treatment inhibited growth of transformed cells expressing a FLT3-ITD in culture (PMID: 31511612). 31511612
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 acute myeloid leukemia sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, an acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) demonstrated sensitivity to Rydapt (midostaurin) treatment, but when co-cultured with human stromal cells, demonstrated resistance to Rydapt (midostaurin) treatment in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins acute myeloid leukemia sensitive 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 sensitive Midostaurin Guideline Actionable Rydapt (midostaurin) is included in guidelines as maintenance therapy for patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org). detail...
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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 Ipatasertib + Palbociclib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Ibrance (palbociclib) and Ipatasertib (GDC-0068) 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 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 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 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 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 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 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 predicted - sensitive IACS-13909 Preclinical - Cell line xenograft Actionable In a preclinical study, IACS-13909 decreased Erk phosphorylation and inhibited proliferation in a acute myeloid leukemia cell line harboring a FLT3-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 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 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 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 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 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 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 cells expressing a FLT3-ITD mutation in culture (PMID: 33391463). 33391463
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-ITD mutations, and decreased viability of patient-derived acute myeloid leukemia blasts harboring FLT3-ITD mutations in culture (PMID: 31310800). 31310800
FLT3 exon 14 ins acute myeloid leukemia sensitive Abivertinib + Omacetaxine mepesuccinate Preclinical - Patient cell culture Actionable In a preclinical study, treatment with the combination of Abivertinib (AC0010) and Synribo (omacetaxine mepesuccinate) resulted in increased apoptosis and reduced viability of acute myeloid leukemia (AML) cell lines harboring FLT3-ITD mutations and decreased viability of patient-derived AML cells harboring FLT3-ITD mutations in culture, and reduced tumor burden and increased survival in cell line xenograft models compared to either agent alone (PMID: 31310800). 31310800
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive OTS167 Preclinical - Patient cell culture Actionable In a preclinical study, OTS167 treatment induced cell death in patient-derived acute myeloid leukemia cells harboring FLT3-ITD in culture (PMID: 33658483). 33658483
FLT3 exon 14 ins acute myeloid leukemia sensitive Gilteritinib + OTS167 Preclinical - Cell line xenograft Actionable In a preclinical study, combination treatment with OTS167 and Xospata (gilteritinib) synergistically inhibited cell viability and led to inhibition of colony formation in acute myeloid leukuemia (AML) cell lines harboring a FLT3-ITD and patient-derived AML cell lines with a FLT3-ITD in culture, and led to improved overall survival and reduction of leukemia burden in a cell line xenograft model (PMID: 33658483). 33658483
FLT3 exon 14 ins hematologic cancer sensitive KX2-391 Preclinical - Cell culture Actionable In a preclinical study, KX2-391 treatment inhibited cell viability, decreased downstream signaling, and induced apoptosis in cells expressing a FLT3-ITD mutation in culture (PMID: 34217323). 34217323
FLT3 exon 14 ins acute myeloid leukemia sensitive KX2-391 Preclinical - Patient cell culture Actionable In a preclinical study, KX2-391 treatment inhibited cell viability and decreased downstream signaling in acute myeloid leukemia cell lines and patient-derived cells harboring a FLT3-ITD mutation in culture (PMID: 34217323). 34217323
FLT3 exon 14 ins acute myeloid leukemia sensitive CUDC-907 + Gilteritinib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of CUDC-907 (fimepinostat) and Xospata (gilteritinib) synergistically inhibited cell growth, decreased Flt3 signaling, and induced apoptosis in patient-derived acute myeloid leukemia cells harboring FLT3-ITD mutations in culture, and resulted in prolonged survival compared to either agent alone in cell line xenograft models (PMID: 34099621). 34099621
FLT3 exon 14 ins acute myeloid leukemia sensitive AZD1480 + CUDC-907 Preclinical - Cell culture Actionable In a preclinical study, the combination of CUDC-907 (fimepinostat) and AZD1480 inhibited phosphorylation of Stat5 and induced apoptosis in acute myeloid leukemia cell lines harboring FLT3-ITD mutations in culture, and demonstrated improved activity over either agent alone (PMID: 34099621). 34099621
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive APG-2575 + HQP1351 Preclinical - Pdx & cell culture Actionable In a preclinical study, combination treatment with GZD824 (HQP1351) and APG-2575 induced apoptosis to a greater degree than either therapy alone in acute myeloid leukemia cells harboring FLT3-ITD in culture, and resulted in a synergistic tumor burden reduction in a patient-derived xenograft (PDX) model of acute myeloid leukemia harboring FLT3-ITD and inhibited tumor growth in a cell line xenograft model with a T/C ratio of 2.8% (PMID: 34710737). 34710737
FLT3 exon 14 ins acute myeloid leukemia sensitive ASTX029 Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cell lines harboring FLT3-ITD mutations were sensitive to treatment with ASTX029 in culture (PMID: 34330842). 34330842
FLT3 exon 14 ins hematologic cancer sensitive Dovitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells harboring FLT3-ITD were sensitive to treatment with Dovitinib (TKI258) in culture, demonstrating decreased cell viability (PMID: 29296813). 29296813
FLT3 exon 14 ins hematologic cancer sensitive NVP-BSK805 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD were sensitive to treatment with NVP-BSK805 in culture, demonstrating decreased cell viability (PMID: 29296813). 29296813
FLT3 exon 14 ins hematologic cancer sensitive NVP-BVB808 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD were sensitive to treatment with NVP-BVB808 in culture, demonstrating decreased cell viability (PMID: 29296813). 29296813
FLT3 exon 14 ins acute myeloid leukemia sensitive ONO-7475 Preclinical - Pdx & cell culture Actionable In a preclinical study, ONO-7475 treatment inhibited Erk phosphorylation and cell viability in acute myeloid leukemia cell lines harboring a FLT3-ITD mutation in culture, and reduced leukemia burden and prolonged survival in patient-derived xenograft (PDX) and cell line xenograft models (PMID: 34732043). 34732043
FLT3 exon 14 ins acute myeloid leukemia sensitive ONO-7475 + Venetoclax Preclinical - Pdx & cell culture Actionable In a preclinical study, the combination of ONO-7475 and Venclexta (venetoclax) synergistically inhibited cell viability and induced apoptosis in acute myeloid leukemia cell lines harboring a FLT3-ITD mutation in culture, and reduced leukemia burden and prolonged overall survival in patient-derived xenograft (PDX) and cell line xenograft models with increased efficacy over either agent alone (PMID: 34732043). 34732043
FLT3 exon 14 ins acute myeloid leukemia sensitive PF-04691502 + Quizartinib Preclinical - Cell culture Actionable In a preclinical study, the combination of PF-04691502 and Vanflyta (quizartinib) induced apoptosis and cell-cycle arrest and synergistically inhibited viability of an acute myeloid leukemia cell line harboring a FLT3-ITD mutation in culture (PMID: 34555701). 34555701
FLT3 exon 14 ins hematologic cancer sensitive Momelotinib Preclinical - Cell culture Actionable In a preclinical study, Momelotinib (CYT387) decreased phosphorylation of Flt3 and Stat5 and inhibited proliferation of transformed cells expressing a FLT3-ITD mutation in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins acute myeloid leukemia sensitive Momelotinib Preclinical - Cell line xenograft Actionable In a preclinical study, Momelotinib (CYT387) inhibited proliferation of acute myeloid leukemia cell lines and patient-derived cells harboring FLT3-ITD mutations in culture, and resulted in prolonged survival and reduced leukemic burden in cell line xenograft models (PMID: 34768286). 34768286
FLT3 exon 14 ins hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive Gilteritinib + Venetoclax Phase I Actionable In a Phase Ib trial, combination treatment with Venclexta (venetoclax) and Xospata (gilteritinib) demonstrated clinical activity in patients with acute myeloid leukemia harboring FLT3 internal tandem duplication (ITD) or tyrosine kinase domain mutations, leading to a a modified composite complete response (mCRc) rate of 75% (42/56), duration of response of 4.9 mo., and median overall survival of 10 mo., with a mCRc of 82% (36/44) in patients with FLT3-ITD mutations (PMID: 35849791; NCT03625505). 35849791
FLT3 exon 14 ins acute myeloid leukemia sensitive Saridegib + Sorafenib Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of Nexavar (sorafenib) and Saridegib (IPI-926) resulted in significantly decreased cell proliferation compared to Nexavar (sorafenib) alone in two acute myeloid leukemia cell lines harboring FLT3-ITD mutations in culture (PMID: 26062848). 26062848
FLT3 exon 14 ins acute myeloid leukemia sensitive Sonidegib + Sorafenib Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of Nexavar (sorafenib) and Odomzo (sonidegib) resulted in significantly decreased cell proliferation compared to Nexavar (sorafenib) alone in an acute myeloid leukemia cell line harboring a FLT3-ITD mutation in culture (PMID: 26062848). 26062848
FLT3 exon 14 ins hematologic cancer sensitive CG-806 Preclinical - Cell culture Actionable In a preclinical study, CG-806 inhibited proliferation of a cell line expressing a FLT3 exon 14 insertion (ITD) mutation in culture (PMID: 35499387). 35499387
FLT3 exon 14 ins acute myeloid leukemia sensitive Crenolanib + Sorafenib Clinical Study Actionable In a clinical study, combination Nexavar (sorafenib) and Crenolanib (CP-868596) resulted in 2 complete remissions, 1 complete remission with incomplete blood count recovery, and 1 partial response of 8 evaluable pediatric patients with relapsed or refractory FLT3 ITD-positive acute myeloid leukemia, and in preclinical studies, resulted in synergy in cell culture and improved leukemia response and survival in xenograft models compared to either agent alone (PMID: 35344039). 35344039
FLT3 exon 14 ins acute myeloid leukemia sensitive Sitravatinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Sitravatinib (MGCD516) inhibited proliferation and induced cell cycle arrest in acute myeloid leukemia cells harboring a FLT3-ITD mutation in culture, increased median survival to 59 days vs 30 days in the vehicle-treated group in a cell line xenograft model, and resulted in a reduced leukemia burden in patient-derived xenograft (PDX) models compared to either Xospata (gilteritinib) or Vanflyta (quizartinib) (PMID: 36691065). 36691065
FLT3 exon 14 ins hematologic cancer sensitive Sitravatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Sitravatinib (MGCD516) inhibited proliferation of transformed hematologic cells expressing a FLT3-ITD mutation in culture, and increased the median survival to 26 days vs 20 days in the Xospata (gilteritinib)-treated group in a cell line xenograft model (PMID: 36691065). 36691065
FLT3 exon 14 ins hematologic cancer predicted - sensitive PHI-101 Preclinical - Cell line xenograft Actionable In a preclinical study, PHI-101 induced tumor regression in a cell line xenograft model expressing a FLT3-ITD mutation (Blood (2020) 136 (Supplement 1): 802). detail...
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive PHI-101 Preclinical - Patient cell culture Actionable In a preclinical study, PHI-101 decreased proliferation and induced apoptosis in patient-derived acute myeloid leukemia samples harboring a FLT3-ITD mutation in culture (Blood (2020) 136 (Supplement 1): 802). detail...
FLT3 exon 14 ins hematologic cancer sensitive Pacritinib Preclinical - Cell culture Actionable In a preclinical study, Vonjo (pacritinib) inhibited kinase activity, phosphorylation of Flt3 and Stat5, and viability in a transformed cell line expressing a FLT3-ITD mutation in culture (PMID: 31102119). 31102119
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive Cytarabine + Daunorubicin + Pacritinib Phase I Actionable In a Phase I trial, treatment with Vonjo (pacritinib) in combination with Cytosar-U (cytarabine) and Cerubidine (daunorubicin) resulted in 2 complete responses and 2 stable disease in 4 evaluable patients with acute myeloid leukemia harboring a FLT3-ITD mutation and resulted in a median overall survival of 292 days and a response rate of 23.1% when combined with either the combination of Cytosar-U (cytarabine) and Cerubidine (daunorubicin) or Dacogen (decitabine) (PMID: 31102119; NCT02323607). 31102119
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive Decitabine + Pacritinib Phase I Actionable In a Phase I trial, treatment with Vonjo (pacritinib) in combination with Dacogen (decitabine) resulted in morphologic leukemia free state in 1 patient and stable disease in 5 of 8 patients with acute myeloid leukemia harboring a FLT3-ITD mutation, and resulted in a median overall survival of 292 days and a response rate of 23.1% when combined with either the combination of Cytosar-U (cytarabine) and Cerubidine (daunorubicin) or Dacogen (decitabine) (PMID: 31102119; NCT02323607). 31102119
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive BMF-500 Preclinical - Patient cell culture Actionable In a preclinical study, BMF-500 decreased viability of patient-derived acute myeloid leukemia cells harboring a FLT3-ITD mutation in culture (Blood (2022) 140 (Supplement 1): 6191-6192). detail...
FLT3 exon 14 ins hematologic cancer sensitive PLM-101 Preclinical - Cell culture Actionable In a preclinical study, PLM-101 inhibited kinase activity and proliferation in cells expressing a FLT3-ITD mutation in culture (PMID: 37392657). 37392657
FLT3 exon 14 ins acute myeloid leukemia sensitive PLM-101 Preclinical - Cell line xenograft Actionable In a preclinical study, PLM-101 induced apoptosis and cell cycle arrest and inhibited Flt3 phosphorylation, downstream signaling, and proliferation in acute myeloid leukemia cell lines harboring a FLT3-ITD mutation in culture and inhibited tumor growth in cell line xenograft models (PMID: 37392657). 37392657
FLT3 exon 14 ins acute myeloid leukemia sensitive Cytarabine + Midostaurin Guideline Actionable Rydapt (midostaurin) in combination with Cytosar-U (cytarabine) is included in guidelines as consolidation therapy for patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org). detail...
FLT3 exon 14 ins acute myeloid leukemia sensitive RMC-4550 Preclinical - Cell culture Actionable In a preclinical study, RMC-4550 inhibited viability in acute myeloid leukemia cell lines harboring FLT3 ITD in culture (PMID: 37992684). 37992684
FLT3 exon 14 ins acute myeloid leukemia sensitive TP-0184 Preclinical - Pdx & cell culture Actionable In a preclinical study, TP-0184 inhibited proliferation and growth of acute myeloid leukemia cells harboring a FLT3-ITD mutation in culture, and inhibited tumor growth and improved survival in cell line and patient-derived xenograft models (PMID: 38007585). 38007585
FLT3 exon 14 ins acute myeloid leukemia sensitive TP-0184 + Venetoclax Preclinical - Cell culture Actionable In a preclinical study, the combination of TP-0184 and Venclexta (venetoclax) synergistically inhibited proliferation of acute myeloid leukemia cells harboring a FLT3-ITD in culture, and inhibited tumor growth and prolonged survival in a cell line xenograft model (PMID: 38007585). 38007585
FLT3 exon 14 ins acute myeloid leukemia sensitive RMC-4550 + Venetoclax Preclinical - Pdx & cell culture Actionable In a preclinical study, the combination of RMC-4550 and Venclexta (venetoclax) synergistically inhibited viability and induced apoptosis in acute myeloid leukemia cell lines harboring FLT3 ITD in culture, reduced tumor burden and improved survival in a cell line xenograft model, and reduced leukemia burden in a patient-derived xenograft (PDX) model (PMID: 37992684). 37992684
FLT3 exon 14 ins acute myeloid leukemia sensitive Trametinib + Venetoclax Preclinical - Cell culture Actionable In a preclinical study, the combination of Venclexta (venetoclax) and Mekinist (trametinib) synergistically inhibited proliferation in acute myeloid leukemia cell lines harboring FLT3 ITD in culture (PMID: 37992684). 37992684
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive HC-7366 + Venetoclax Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with the combination of HC-7366 and Venclexta (venetoclax) resulted in tumor regression in a cell line xenograft model of acute myeloid leukemia harboring a FLT3 ITD mutation (Blood (2023) 142 (Supplement 1): 2943). detail...
FLT3 exon 14 ins hematologic cancer sensitive Foretinib Preclinical - Cell line xenograft Actionable In a preclinical study, Foretinib (GSK1363089) inhibited growth of cultured cells expressing FLT3-ITD mutations, and led to decreased tumor burden and improved survival in a cell line xenograft model (PMID: 38231480). 38231480
FLT3 exon 14 ins acute myeloid leukemia sensitive Foretinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Foretinib (GSK1363089) inhibited viability of cell lines and primary patient-derived acute myeloid leukemia cells harboring FLT3-ITD in culture, led to decreased tumor burden and improved survival in a cell line and a patient-derived xenograft (PDX) model (PMID: 38231480). 38231480
FLT3 exon 14 ins acute myeloid leukemia sensitive Azacitidine + Gilteritinib + Venetoclax Phase Ib/II Actionable In a Phase I/II trial, Venclexta (venetoclax), Vidaza (azacitidine), and Xospata (gilteritinib) treatment demonstrated safety in acute myeloid leukemia patients with FLT3-ITD or FLT3 D835 mutations and led to a combined complete remission (CR)/CR with incomplete hematologic recovery (CR/CRi) rate of 96% and a median relapse-free survival and median overall survival not reached in newly diagnosed patients (n=30), and a CR/CRi rate of 27% in relapsed/refractory patients (n=22) (PMID: 38277619; NCT04140487). 38277619