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Profile Name | FLT3 exon 14 ins FLT3 F691L |
Gene Variant Detail | |
Relevant Treatment Approaches |
Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|---|
FLT3 exon 14 ins FLT3 F691L | acute myeloid leukemia | resistant | Gilteritinib | Case Reports/Case Series | Actionable | In a Phase I trial, three patients with acute myeloid leukemia harboring FLT3 ITD with FLT3 F691L were resistant to Xospata (gilteritinib) (PMID: 32040554). | 32040554 | |
FLT3 exon 14 ins FLT3 F691L | acute myeloid leukemia | sensitive | MRX-2843 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant acute myeloid leukemia cells harboring FLT3 internal tandem duplication (ITD) and F691L in culture, and prolonged survival in cell line xenograft models (PMID: 27158668). | 27158668 | |
FLT3 exon 14 ins FLT3 F691L | acute myeloid leukemia | sensitive | FF-10101 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, FF-10101 inhibited Flt3 autophosphorylation and growth of leukemic cell lines and inhibited growth of cell line xenografts with FLT3-ITD/F691L compound mutations (PMID: 29187377). | 29187377 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | sensitive | Dubermatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Dubermatinib (TP-0903) treatment decreased phosphorylation of Flt3 and Stat5 and inhibited growth of transformed cells expressing a FLT3-ITD mutation and FLT3 F691L in culture, and reduced peripheral blood tumor burden in cell line xenograft models (PMID: 33268594). | 33268594 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | sensitive | LT-171-861 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, LT-171-861 inhibited cell viability and decreased FLT3 phosphorylation in transformed cells expressing a FLT3-ITD mutation and FLT3 F691L in culture, and inhibited tumor growth and prolonged survival in cell line xenograft models (PMID: 33391463). | 33391463 | |
FLT3 exon 14 ins FLT3 F691L | acute myeloid leukemia | resistant | Crenolanib + Sorafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, FLT3 F691L 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 F691L | 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 F691L (Cancer Res 2021;81(13_Suppl):Abstract nr 1257). | detail... | |
FLT3 exon 14 ins FLT3 F691L | 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 with FLT3 F691L in culture, and increased the median survival to 26 days vs 14.5 days in the vehicle-treated group in a cell line xenograft model (PMID: 36691065). | 36691065 | |
FLT3 exon 14 ins FLT3 F691L | 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 F691L in the context of a FLT3-ITD mutation (Blood (2020) 136 (Supplement 1): 802). | detail... | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | resistant | Quizartinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, cells expressing FLT3-ITD and FLT3 F691L were resistant to treatment with Vanflyta (quizartinib) in culture and in a cell line xenograft model (PMID: 38231480). | 38231480 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | resistant | Gilteritinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Xospata (gilteritinib) was not active against cells expressing FLT3-ITD with FLT3 F691L in culture and resulted in minimal survival benefit in a cell line xenograft model (PMID: 38231480). | 38231480 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | sensitive | Foretinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Foretinib (GSK1363089) inhibited viability of cultured cells expressing FLT3-ITD with FLT3 F691L, and inhibited tumor cell growth in a cell line xenograft model (PMID: 38231480). | 38231480 | |
FLT3 exon 14 ins FLT3 F691L | acute myeloid leukemia | sensitive | Ningetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Ningetinib (CT053PTSA) decreased leukemic burden in a cell line xenograft model of acute myeloid leukemia harboring a FLT3-ITD and expressing FLT3 F691L (PMID: 38978049). | 38978049 | |
FLT3 exon 14 ins FLT3 F691L | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing FLT3 ITD and F691L in culture (PMID: 27780853). | 27780853 | |
FLT3 exon 14 ins FLT3 F691L | Advanced Solid Tumor | resistant | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and F691L were resistant to Nexavar (sorafenib) in culture (PMID: 23392356). | 23392356 | |
FLT3 exon 14 ins FLT3 F691L | Advanced Solid Tumor | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and F691L were resistant to Vanflyta (quizartinib) in culture (PMID: 23392356). | 23392356 | |
FLT3 exon 14 ins FLT3 F691L | Advanced Solid Tumor | sensitive | MRX-2843 | Preclinical - Cell culture | Actionable | In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant transformed cells over expressing both FLT3 internal tandem duplication (ITD) and F691L in culture (PMID: 27158668). | 27158668 | |
FLT3 exon 14 ins FLT3 F691L | acute myeloid leukemia | decreased response | Lestaurtinib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 F691L demonstrated a decreased response to Lestaurtinib (CEP-701) compared to treated cells harboring a FLT3 ITD and expressing FLT3 Y842C (Blood 2009 114:3776). | detail... | |
FLT3 exon 14 ins FLT3 F691L | acute myeloid leukemia | decreased response | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 F691L demonstrated a decreased response to Rydapt (midostaurin) 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 | SKI-G-801 | Preclinical - Cell culture | Actionable | In a preclinical study, cells co-expressing a FLT3 internal tandem duplication and FLT3 F691L were sensitive to SKI-G-801 in culture, demonstrating inhibition of cell growth and inhibition of Flt3 autophosphorylation (PMID: 24532805). | 24532805 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | 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 F691L in culture (PMID: 35499387). | 35499387 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | predicted - resistant | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing both FLT3 exon 14 insertions (ITD) and FLT3 F691L were less sensitive to Crenolanib-induced growth inhibition compared to cells expressing FLT3 ITD in culture (PMID: 31309543). | 31309543 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing both FLT3 exon 14 insertions (ITD) and FLT3 F691L were less sensitive to Vanflyta (quizartinib)-induced growth inhibition compared to cells expressing FLT3 ITD in culture (PMID: 31309543). | 31309543 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | resistant | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing both FLT3 exon 14 insertions (ITD) and FLT3 F691L were less sensitive to Xospata (gilteritinib)-induced growth inhibition compared to cells expressing FLT3 ITD in culture (PMID: 31309543). | 31309543 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | resistant | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) did not inhibit growth of transformed hematologic cells expressing both FLT3 exon 14 insertions (ITD) and FLT3 F691L in culture (PMID: 31309543). | 31309543 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | resistant | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing both FLT3 exon 14 insertions (ITD) and FLT3 F691L were resistant to Nexavar (sorafenib)-induced growth inhibition in culture (PMID: 31309543). | 31309543 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | decreased response | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing both FLT3 exon 14 insertions (ITD) and FLT3 F691L were less sensitive to Ayvakit (avapritinib)-induced growth inhibition compared to cells expressing FLT3 ITD in culture (PMID: 31309543). | 31309543 | |
FLT3 exon 14 ins FLT3 F691L | Advanced Solid Tumor | sensitive | LAM-003 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing FLT3 internal tandem duplication (ITD) and FLT3 F691L demonstrated sensitivity to LAM-003 treatment in culture (PMID: 31751472). | 31751472 | |
FLT3 exon 14 ins FLT3 F691L | myeloid leukemia | resistant | A-419259 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed myeloid leukemia cells co-expressing FLT-ITD and FLT3 F691L demonstrated resistance to A-419259 treatment in culture (PMID: 31790499). | 31790499 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | resistant | KW-2449 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 F691L were resistant to treatment with KW-2449 in culture (PMID: 22858906). | 22858906 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | resistant | Momelotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 F691L demonstrated resistance to Momelotinib (CYT387) in culture (PMID: 34768286). | 34768286 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | resistant | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 F691L demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33780043). | 33780043 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | predicted - resistant | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 F691L demonstrated resistance to treatment with Crenolanib in culture (PMID: 33780043). | 33780043 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 F691L demonstrated resistance to treatment with Vanflyta (quizartinib) in culture (PMID: 33780043). | 33780043 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | resistant | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 F691L demonstrated resistance to treatment with Rydapt (midostaurin) in culture (PMID: 33780043). | 33780043 | |
FLT3 exon 14 ins FLT3 F691L | acute myeloid leukemia | sensitive | FF-10101 | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring FLT3-ITD and FLT3 F691L demonstrated sensitivity to treatment with FF-10101 in culture, but were less sensitive compared to cells harboring FLT3-ITD alone (PMID: 35395091). | 35395091 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | sensitive | FF-10101 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells harboring FLT3-ITD and FLT3 F691L demonstrated sensitivity to treatment with FF-10101 in culture, but were less sensitive compared to cells expressing FLT3-ITD alone (PMID: 35395091). | 35395091 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | resistant | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing FLT3 ITD with FLT3 F691L demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 32040554). | 32040554 | |
FLT3 exon 14 ins FLT3 F691L | acute myeloid leukemia | resistant | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring FLT3 ITD with FLT3 F691L were resistant to Xospata (gilteritinib) in culture (PMID: 32040554). | 32040554 | |
FLT3 exon 14 ins FLT3 F691L | acute myeloid leukemia | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring FLT3 ITD with FLT3 F691L were resistant to Vanflyta (quizartinib) in culture (PMID: 32040554). | 32040554 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | resistant | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 F691L were moderately resistant to Xospata (gilteritinib) treatment in culture (PMID: 35395091). | 35395091 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 F691L were resistant to Vanflyta (quizartinib) treatment in culture (PMID: 35395091). | 35395091 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | resistant | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 F691L were moderately resistant to Rydapt (midostaurin) treatment in culture (PMID: 35395091). | 35395091 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | resistant | Lestaurtinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 F691L demonstrated resistance to Lestaurtinib (CEP-701) in culture (PMID: 34768286). | 34768286 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | resistant | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 F691L demonstrated resistance to Nexavar (sorafenib) in culture (PMID: 34768286). | 34768286 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | conflicting | Pacritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 F691L demonstrated resistance to Vonjo (pacritinib) in culture (PMID: 34768286). | 34768286 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | predicted - resistant | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 F691L, and FLT3 D835Y were resistant to Crenolanib (CP-868596) in culture (PMID: 34768286). | 34768286 | |
FLT3 exon 14 ins FLT3 F691L | 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 F691L in culture (PMID: 31102119). | 31102119 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | sensitive | PLM-101 | Preclinical - Cell culture | Actionable | In a preclinical study, PLM-101 inhibited proliferation in cells expressing FLT3 F691L in the context of a FLT3-ITD mutation in culture (PMID: 37392657). | 37392657 | |
FLT3 exon 14 ins FLT3 F691L | acute myeloid leukemia | sensitive | RMC-4550 | Preclinical - Cell culture | Actionable | In a preclinical study, RMC-4550 inhibited viability in an acute myeloid leukemia cell line harboring FLT3 ITD and expressing FLT3 F691L in culture (PMID: 37992684). | 37992684 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | predicted - sensitive | PHI-101 | Preclinical - Biochemical | Actionable | In a preclinical study, PHI-101 demonstrated activity against FLT3 F691L in the context of a FLT3-ITD mutation in culture (Cancer Res 2020;80(16 Suppl):Abstract nr 4226). | detail... | |
FLT3 exon 14 ins FLT3 F691L | Advanced Solid Tumor | sensitive | Pexidartinib | Preclinical | Actionable | In a preclinical study, PLX3397 inhibited growth of transformed cells expressing a compound FLT3 F691L/FLT3-ITD mutation in culture (PMID: 25847190). | 25847190 | |
FLT3 exon 14 ins FLT3 F691L | leukemia | sensitive | Pexidartinib | Preclinical | Actionable | In a preclinical study, PLX3397 inhibited proliferation of human leukemia cells harboring both FLT3-ITD and FLT3 F691L in culture (PMID: 25847190). | 25847190 | |
FLT3 exon 14 ins FLT3 F691L | leukemia | sensitive | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited proliferation and induced apoptosis in FLT3 inhibitor-resistant leukemia cell lines harboring FLT3 F691L in addition to FLT3 internal tandem duplications (ITD) in culture (PMID: 26822154). | 26822154 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | predicted - sensitive | Tuspetinib | Preclinical | Actionable | In a preclinical study, Tuspetinib (HM43239) treatment inhibited transformed cells expressing FLT3 ITD and F691L in cell culture (Cancer Res 2019;79(13 Suppl):Abstract nr 1293). | detail... | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | sensitive | KX2-391 | Preclinical | Actionable | In a preclinical study, KX2-391 treatment inhibited viability, decreased downstream signaling, and induced apoptosis in cells expressing a FLT3-ITD mutation with FLT3 F691L in culture, and inhibited tumor growth and prolonged survival in mouse models (PMID: 34217323). | 34217323 | |
FLT3 exon 14 ins FLT3 F691L | hematologic cancer | sensitive | Ningetinib | Preclinical | Actionable | In a preclinical study, Ningetinib (CT053PTSA) inhibited Flt3 downstream signaling and viability in a cell line expressing a FLT3-ITD and FLT3 F691L in culture and decreased leukemic burden and prolonged survival in a mouse model (PMID: 38978049). | 38978049 |
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