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Profile Name FLT3 exon 14 ins FLT3 D835Y
Gene Variant Detail

FLT3 D835Y (gain of function)

FLT3 exon 14 ins (gain of function - predicted)

Relevant Treatment Approaches

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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 D835Y Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, FLT3 D835Y conferred resistance to PLX3397 when expressed in a compound mutation with FLT3-ITD in cell culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D835Y leukemia predicted - resistant Pexidartinib Case Reports/Case Series Actionable In a clinical case study, a patient with FLT3-ITD positive leukemia initially responded to Pexidartinib (PLX3397) therapy, but experienced relapse after emergence of FLT3 D835Y on the same allele as the FLT3-ITD mutation (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D835Y Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing a FLT3-ITD mutation and FLT3 D835Y in culture (PMID: 27780853). 27780853
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia sensitive MRX-2843 Preclinical - Cell line xenograft Actionable In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant acute myeloid leukemia cells harboring FLT3 internal tandem duplication (ITD) and D835Y in culture, and prolonged survival in cell line xenograft models (PMID: 27158668). 27158668
FLT3 exon 14 ins FLT3 D835Y Advanced Solid Tumor sensitive MRX-2843 Preclinical - Cell culture Actionable In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant transformed cells over expressing both FLT3 internal tandem duplication (ITD) and D835Y in culture (PMID: 27158668). 27158668
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia sensitive FF-10101 Preclinical - Cell line xenograft Actionable In a preclinical study, FF-10101 inhibited Flt3 autophosphorylation and growth of leukemic cell lines and inhibited growth of cell line xenografts with FLT3-ITD/D835Y compound mutations (PMID: 29187377). 29187377
FLT3 exon 14 ins FLT3 D835Y 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 and FLT3 D835Y in culture (PMID: 35499387). 35499387
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia sensitive LAM-003 Preclinical - Patient cell culture Actionable In a preclinical study, LAM-003 treatment inhibited viability of an acute myeloid leukemia cell line and patient-derived cells harboring FLT3 internal tandem duplication (ITD) and FLT3 D835Y in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia resistant Sorafenib Preclinical - Cell culture Actionable In a preclinical study, an acute myeloid cell line harboring FLT3 internal tandem duplication (ITD) and FLT3 D835Y did not demonstrate sensitivity to Nexavar (sorafenib) treatment in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia resistant Tandutinib Preclinical - Cell culture Actionable In a preclinical study, an acute myeloid cell line harboring FLT3 internal tandem duplication (ITD) and FLT3 D835Y demonstrated resistance to Tandutinib (CT53518) treatment in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins FLT3 D835Y hematologic cancer no benefit Palbociclib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing FLT3 ITD and FLT3 D835Y did not respond to treatment with Ibrance (palbociclib) in culture (PMID: 30544932). 30544932
FLT3 exon 14 ins FLT3 D835Y hematologic cancer no benefit Danusertib + Palbociclib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing FLT3 ITD and FLT3 D835Y did not respond to the combination treatment of Ibrance (palbociclib) and Danusertib (PHA-739358) in culture (PMID: 30544932). 30544932
FLT3 exon 14 ins FLT3 D835Y hematologic cancer predicted - sensitive HQP1351 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 D835Y demonstrated decreased proliferation in response to GZD824 (HQP1351) in culture, but were less sensitive to treatment than cells co-expressing FLT3-ITD with other FLT3 kinase domain mutations (PMID: 32247263). 32247263
FLT3 exon 14 ins FLT3 D835Y hematologic cancer predicted - sensitive Tuspetinib Preclinical Actionable In a preclinical study, Tuspetinib (HM43239) treatment inhibited transformed cells expressing FLT3 ITD and D835Y in cell culture (Cancer Res 2019;79(13 Suppl):Abstract nr 1293). detail...
FLT3 exon 14 ins FLT3 D835Y myeloid leukemia resistant A-419259 Preclinical - Cell culture Actionable In a preclinical study, transformed myeloid leukemia cells co-expressing FLT-ITD and FLT3 D835Y demonstrated resistance to A-419259 treatment in culture (PMID: 31790499). 31790499
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia resistant Sorafenib Case Reports/Case Series Actionable In a clinical case study, FLT3 D835Y was identified as an acquired resistance mutation in a patient with acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD) whose disease progressed on Nexavar (sorafenib) after initial response (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia resistant Sorafenib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835Y demonstrated resistance to Nexavar (sorafenib) treatment in culture (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia resistant Quizartinib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835Y demonstrated resistance to Vanflyta (quizartinib) treatment in culture (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia sensitive Gilteritinib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835Y demonstrated sensitivity to Xospata (gilteritinib) treatment in culture, resulting in reduced cell viability (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia conflicting Crenolanib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835Y demonstrated sensitivity to Crenolanib (CP-868596) treatment in culture, resulting in reduced cell viability (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia predicted - resistant Midostaurin Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835Y demonstrated resistance to Rydapt (midostaurin) treatment in culture (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia sensitive Dubermatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Dubermatinib (TP-0903) treatment resulted in cell cycle arrest and apoptosis, induced differentiation, and inhibited growth of acute myeloid leukemia cells harboring a FLT3-ITD mutation and FLT3 D835Y in culture, and reduced tumor growth and increased survival in cell line xenograft models (PMID: 33268594). 33268594
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia sensitive Gilteritinib Preclinical - Cell line xenograft Actionable In a preclinical study, Xospata (gilteritinib) treatment inhibited growth of acute myeloid leukemia cells harboring a FLT3-ITD mutation and FLT3 D835Y in culture, and reduced tumor growth and increased survival in cell line xenograft models (PMID: 33268594). 33268594
FLT3 exon 14 ins FLT3 D835Y hematologic cancer sensitive Dubermatinib Preclinical - Cell culture Actionable In a preclinical study, Dubermatinib (TP-0903) inhibited growth of transformed cells expressing a FLT3-ITD mutation and FLT3 D835Y in culture (PMID: 33268594). 33268594
FLT3 exon 14 ins FLT3 D835Y hematologic cancer predicted - sensitive LT-171-861 Preclinical - Cell culture Actionable In a preclinical study, LT-171-861 inhibited cell viability and decreased FLT3 phosphorylation in transformed cells expressing a FLT3-ITD mutation and FLT3 D835Y in culture (PMID: 33391463). 33391463
FLT3 exon 14 ins FLT3 D835Y 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 with FLT3 D835Y in culture (PMID: 34217323). 34217323
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia predicted - sensitive KX2-391 Preclinical - Patient cell culture Actionable In a preclinical study, KX2-391 treatment inhibited cell viability and decreased Flt3 phosphorylation in patient-derived acute myeloid leukemia cell lines harboring a FLT3-ITD mutation with FLT3 D835Y in culture (PMID: 34217323). 34217323
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia predicted - resistant Pexidartinib Case Reports/Case Series Actionable In a Phase I/II trial, an acute myeloid leukemia patient harboring a FLT3-ITD was found to have acquired FLT3 D535Y following relapse on Turalio (pexidartinib) treatment (PMID: 34103301; NCT01349049). 34103301
FLT3 exon 14 ins FLT3 D835Y 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 FLT3-ITD and FLT3 D835Y in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins FLT3 D835Y 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 and FLT3 D835Y in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835Y 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 and FLT3 D835Y in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835Y hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) resulted in reduced cell viability in transformed cells expressing FLT3 ITD with FLT3 D835Y in culture (PMID: 32040554). 32040554
FLT3 exon 14 ins FLT3 D835Y hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835Y in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) resulted in reduced cell viability in acute myeloid leukemia cells harboring FLT3 ITD with FLT3 D835Y in culture (PMID: 32040554). 32040554
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring FLT3 ITD with FLT3 D835Y were resistant to Vanflyta (quizartinib) in culture (PMID: 32040554). 32040554
FLT3 exon 14 ins FLT3 D835Y 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 and FLT3 D835Y in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835Y hematologic cancer resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 D835Y were resistant to treatment with Vanflyta (quizartinib) in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835Y hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835Y in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835Y hematologic cancer sensitive Lestaurtinib Preclinical - Cell culture Actionable In a preclinical study, Lestaurtinib (CEP-701) inhibited proliferation of transformed cells expressing FLT3-ITD and FLT3 D835Y in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins FLT3 D835Y hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited proliferation of transformed cells expressing FLT3-ITD and FLT3 D835Y in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins FLT3 D835Y hematologic cancer resistant Sorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 D835Y demonstrated resistance to Nexavar (sorafenib) in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins FLT3 D835Y hematologic cancer conflicting Pacritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 D835Y demonstrated resistance to Vonjo (pacritinib) in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins FLT3 D835Y hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 D835Y were sensitive to Rydapt (midostaurin) treatment in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins FLT3 D835Y hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 D835Y were sensitive to Crenolanib (CP-868596) treatment in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia resistant Sorafenib Preclinical - Cell line xenograft Actionable In a preclinical study, FLT3 D835Y was identified as a secondary resistance mutation in FLT3 ITD-positive acute myeloid leukemia cell line xenograft models that progressed on Nexavar (sorafenib) (PMID: 35344039). 35344039
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia resistant Crenolanib + Sorafenib Preclinical - Cell line xenograft Actionable In a preclinical study, FLT3 D835Y was identified as a secondary resistance mutation in FLT3 ITD-positive acute myeloid leukemia cell line xenograft models that progressed on the combination of Crenolanib (CP-868596) and Nexavar (sorafenib) (PMID: 35344039). 35344039
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia conflicting Crenolanib Preclinical - Cell line xenograft Actionable In a preclinical study, FLT3 D835Y was identified as a secondary resistance mutation in FLT3 ITD-positive acute myeloid leukemia cell line xenograft models that progressed on Crenolanib (CP-868596) (PMID: 35344039). 35344039
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia predicted - sensitive Tuspetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Tuspetinib (HM43239) treatment resulted in tumor regression in a cell line xenograft model of acute myeloid leukemia expressing a FLT3 ITD mutation and FLT3 D835Y (Cancer Res 2021;81(13_Suppl):Abstract nr 1257). detail...
FLT3 exon 14 ins FLT3 D835Y hematologic cancer resistant Sitravatinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD mutation with FLT3 D835Y were resistant to treatment with Sitravatinib (MGCD516) in culture (PMID: 36691065). 36691065
FLT3 exon 14 ins FLT3 D835Y hematologic cancer predicted - sensitive PHI-101 Preclinical - Cell line xenograft Actionable In a preclinical study, PHI-101 decreased leukemia burden in a cell line xenograft model expressing FLT3 D835Y in the context of a FLT3-ITD mutation (Blood (2020) 136 (Supplement 1): 802). detail...
FLT3 exon 14 ins FLT3 D835Y hematologic cancer conflicting Pacritinib Preclinical - Cell culture Actionable In a preclinical study, Vonjo (pacritinib) inhibited phosphorylation of Flt3 and Stat5 and viability in a transformed cell line expressing a FLT3-ITD mutation and FLT3 D835Y in culture (PMID: 31102119). 31102119
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia sensitive Pacritinib Preclinical - Cell culture Actionable In a preclinical study, Vonjo (pacritinib) inhibited viability in an acute myeloid leukemia cell line harboring a FLT3-ITD mutation and FLT3 D835Y in culture (PMID: 31102119). 31102119
FLT3 exon 14 ins FLT3 D835Y hematologic cancer sensitive PLM-101 Preclinical - Cell culture Actionable In a preclinical study, PLM-101 inhibited proliferation in cells expressing FLT3 D835Y in the context of a FLT3-ITD mutation in culture (PMID: 37392657). 37392657