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| Gene | FLT3 |
| Variant | F594_D600dup |
| Impact List | duplication |
| Protein Effect | gain of function - predicted |
| Gene Variant Descriptions | FLT3 F594_D600dup indicates the insertion of seven duplicate amino acids, phenylalanine (F)-594 through aspartic acid (D)-600, in the juxtamembrane domain of the Flt3 protein (PMID: 14759363). F594_D600dup has not been biochemically characterized, but can be predicted to lead to activation of Flt3 based on the effects of other Flt3 internal tandem duplication (ITD) mutations (PMID: 12970773, PMID: 9737679, PMID: 11090077). |
| Associated Drug Resistance | |
| Category Variants Paths |
FLT3 mutant FLT3 act mut FLT3 exon 14 ins FLT3 F594_D600dup FLT3 mutant FLT3 exon14 FLT3 exon 14 ins FLT3 F594_D600dup |
| Transcript | NM_004119.3 |
| gDNA | chr13:g.28034119_28034139 |
| cDNA | c.1780_1800 |
| Protein | p.F594_D600 |
| Source Database | RefSeq |
| Genome Build | GRCh38/hg38 |
| Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
|---|---|---|---|---|---|
| NM_004119.3 | chr13:g.28034119_28034139 | c.1780_1800 | p.F594_D600 | RefSeq | GRCh38/hg38 |
| NM_004119 | chr13:g.28034118_28034119insGTCATACTCATACTCCCTAAA | c.1800_1801insTTTAGGGAGTATGAGTATGAC | p.F594_D600dup | RefSeq | GRCh38/hg38 |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| 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 | 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 | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited growth of transformed hematologic cells expressing FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). | 31309543 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | 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 | 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 | 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 | Sorafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) combined with Mekinist (trametinib) enhanced apoptosis in acute myeloid leukemia cell lines harboring FLT3 internal tandem duplication (ITD) mutations in culture (PMID: 28923853). | 28923853 |
| FLT3 exon 14 ins | acute myeloid leukemia | predicted - sensitive | 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 | 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 | 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 | 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 | 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 | MRX-2843 + Venetoclax | Preclinical - Patient cell culture | Actionable | In a preclinical study, the combination of MRX-2843 and Venclexta (venetoclax) induced apoptosis in acute myeloid leukemia (AML) cell lines harboring a FLT3-ITD, including cell lines resistant to Cytosar-U (cytarabine), and induced apoptosis and inhibited colony growth in primary AML cells harboring a FLT3-ITD in culture (PMID: 38968731). | 38968731 |
| 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 | hematologic cancer | sensitive | Olverembatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Olverembatinib (HQP1351) inhibited growth of transformed cells expressing FLT3-ITD in culture (PMID: 32247263). | 32247263 |
| FLT3 exon 14 ins | acute myeloid leukemia | predicted - sensitive | Decitabine + Quizartinib + Venetoclax | Phase Ib/II | Actionable | In a Phase I/II trial, treatment with the combination of Vanflyta (quizartinib), Venclexta (venetoclax), and Dacogen (decitabine) resulted in a composite complete remission (CRc) rate of 68% (27/40), a median overall survival (OS) of 7.1 months, and a 1-year OS rate of 22% in relapsed/refractory acute myeloid leukemia patients with FLT3-ITD mutations, and in the frontline setting, the combination treatment resulted in a CRc of 100% (10/10) (Blood (2023) 142 (Supplement 1): 158; NCT03661307). | detail... |
| 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 | 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 | leukemia | sensitive | Pexidartinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX3397 inhibited proliferation of human leukemia cells harboring FLT3-ITD in culture and in cell line xenograft models (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins | acute myeloid leukemia | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | leukemia | predicted - sensitive | GMI-1359 + Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, combination of GMI-1359 with Nexavar (sorafenib) enhanced apoptosis compared to Nexavar (sorafenib) alone (48.9% vs 36.6%) in leukemia cell lines harboring FLT3 internal tandem duplication (ITD) mutations (Blood 2015 126(23):3790). | detail... |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | 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 | 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 | sensitive | Cytarabine + Idarubicin + Quizartinib | Guideline | Actionable | Vanflyta (quizartinib) in combination with Idamycin (idarubicin) 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 | Advanced Solid Tumor | sensitive | Pexidartinib | Preclinical | Actionable | In a preclinical study, PLX3397 inhibited proliferation of transformed cells expressing FLT3-ITD in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins | hematologic cancer | sensitive | 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 | 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 | 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 | 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 | 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 | 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 | 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 | Gilteritinib + Metformin | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Xospata (gilteritinib) and Glucophage (metformin) synergistically inhibited viability and induced apoptosis and cell cycle arrest in acute myeloid leukemia cell lines and patient-derived cells harboring a FLT3-ITD mutation in culture, and reduced leukemia burden and increased median survival compared to either drug alone (>70 days vs 46 days (metformin) or 52 days (gilteritinib)) in cell line xenograft models (PMID: 39019012). | 39019012 |
| 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 | 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 | 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 | 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 | 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 | 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 | 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 | predicted - sensitive | Pexidartinib | Phase Ib/II | Actionable | In a Phase I/II trial, treatment with Turalio (pexidartinib) was well-tolerated and resulted in an overall response rate of 21% (19/90) and a composite complete remission (CRc) rate of 11% (10/90) in patients with relapsed/refractory acute myeloid leukemia harboring a FLT3-ITD mutation (PMID: 32330242; NCT01349049). | 32330242 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | 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 | 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 | 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 | 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 | acute myeloid leukemia | sensitive | Olverembatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Olverembatinib (HQP1351) reduced Flt3 and Stat5 phosphorylation, induced cell cycle arrest and apoptosis, and inhibited growth of acute myeloid leukemia cells harboring FLT3-ITD in culture, and suppressed tumor growth, decreased Flt3 activation, and induced apoptosis in cell line xenograft models (PMID: 32247263). | 32247263 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | 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 | 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 | 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 | 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 | 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 | 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 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 | 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 | 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 | 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 | 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 | hematologic cancer | sensitive | Flonoltinib maleate | Preclinical - Cell culture | Actionable | In a preclinical study, Flonoltinib maleate inhibited proliferation of a cell line expressing a FLT3-ITD in culture (PMID: 35256594). | 35256594 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Cytarabine + LT-171-861 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of LT-171-861 and Cytosar-U (cytarabine) synergistically inhibited cell viability in acute myeloid leukemia cell lines harboring FLT3-ITD mutations in culture (PMID: 33391463). | 33391463 |
| FLT3 exon 14 ins | acute myeloid leukemia | 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 | Dubermatinib + Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with the combination of Dubermatinib (TP-0903) and Nexavar (sorafenib) inhibited proliferation of an acute myeloid leukemia cell line harboring a FLT3-ITD in culture (PMID: 39395205). | 39395205 |
| 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 | 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 | 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 | 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 | 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 | acute myeloid leukemia | sensitive | Ningetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Ningetinib (CT053PTSA) induced cell cycle arrest and apoptosis and inhibited Flt3 downstream signaling and viability in acute myeloid leukemia cell lines harboring a FLT3-ITD, inhibited Flt3 downstream signaling and proliferation in patient-derived cells in culture, and decreased leukemic burden in a cell line xenograft model (PMID: 38978049). | 38978049 |
| FLT3 exon 14 ins | acute myeloid leukemia | predicted - sensitive | APG-2575 + Olverembatinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, combination treatment with Olverembatinib (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 | 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 | 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 | 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 | 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 | Selinexor + Sorafenib | Phase Ib/II | Actionable | In a Phase I/II trial, combination of Selinexor and Nexavar (sorafenib) treatment resulted in complete remission in 29% (4/14) and more than 50% blast reduction in 14% (2/14) of patients with acute myeloid leukemia harboring FLT3 ITD and/or D835 mutations (ASH, 59th Annual Meeting and Exposition, Dec 2017, Abstract 1344; NCT01607892). | detail... |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | 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 | 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 | 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 | 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 | 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 | 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 | Bemcentinib + Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with the combination of Bemcentinib (BGB-324) and Nexavar (sorafenib) synergistically inhibited proliferation of an acute myeloid leukemia cell line harboring a FLT3-ITD (PMID: 39395205). | 39395205 |
| 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 - 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 | 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 | 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 | 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 in culture and decreased leukemic burden in a mouse model (PMID: 38978049). | 38978049 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Azacitidine + Gilteritinib + Venetoclax | Clinical Study | Actionable | In a retrospective analysis, real-world treatment with Xospata (gilteritinib), Venclexta (venetoclax), and Vidaza (azacitidine) resulted in a modified composite complete remission rate (mCRc) of 62.1% (18/29) and a 2-yr overall survival (OS) rate of 60.9% in acute myeloid leukemia patients with FLT3-ITD and/or TKD mutations, with an mCRc of 70% (7/10) and a 1-yr OS rate of 80% in patients without prior FLT3 TKI, and an mCRc of 57.9% (11/19) and a 1-yr OS rate of 58.8% with prior FLT3 TKI (PMID: 39180903). | 39180903 |
| 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 |
| 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 | 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 | 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 | 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 | 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 | PD-0325901 + Sorafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) and PD-0325901 synergistically induced apoptosis and inhibited proliferation of acute myeloid leukemia (AML) cell lines harboring FLT3 internal tandem duplication (ITD) mutations in culture, inhibited Erk phosphorylation in FLT3-ITD mutant AML patient cells, and reduced leukemic burden in a FLT3-ITD mutant AML cell line xenograft model (PMID: 28923853). | 28923853 |
| FLT3 exon 14 ins | acute myeloid leukemia | 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 | 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 | 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 | 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 | 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 | 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 | sensitive | A-1210477 + Venetoclax | Preclinical - Cell culture | Actionable | In a preclinical study, A-1210477 and Venclexta (venetoclax) combination treatment synergistically inhibited viability of acute myeloid leukemia cell lines harboring FLT3 internal tandem duplication (ITD) in culture (PMID: 31751472). | 31751472 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Cytarabine + SKI-G-801 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of SKI-G-801 and Cytosar-U (cytarabine) resulted in a synergistic effect, demonstrating greater inhibition of proliferation compared to G-749 alone in acute myeloid leukemia cells harboring a FLT3 internal tandem duplication (PMID: 24532805). | 24532805 |
| FLT3 exon 14 ins | 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 | 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 | not applicable | N/A | Guideline | Prognostic | FLT3 internal tandem duplication (FLT3-ITD) mutations are associated with inferior prognosis in acute myeloid leukemia patients with normal karyotype (NCCN.org). | detail... |
| FLT3 exon 14 ins | hematologic cancer | sensitive | 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 | 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 | 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 | Bemcentinib + Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with the combination of Bemcentinib (BGB-324) and Xospata (gilteritinib) synergistically inhibited proliferation and induced apoptosis in an acute myeloid leukemia cell line harboring a FLT3-ITD (PMID: 39395205). | 39395205 |
| 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 | 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 | Decitabine + Sorafenib | Guideline | Actionable | Nexavar (sorafenib) in combination with Dacogen (decitabine) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org). | detail... |
| FLT3 exon 14 ins | acute myeloid leukemia | predicted - sensitive | 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 | 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 | 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 | 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 | 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 | 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 | Dubermatinib + Gilteritinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, treatment with the combination of Dubermatinib (TP-0903) and Xospata (gilteritinib) inhibited proliferation and synergistically induced apoptosis in an acute myeloid leukemia cell line and in patient-derived cells harboring a FLT3-ITD in culture, and led to a greater decrease in leukemic burden and improved survival compared to treatment with either agent alone in a cell line xenograft model (PMID: 39395205). | 39395205 |
| 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 | 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 | Flonoltinib maleate | Preclinical - Cell culture | Actionable | In a preclinical study, Flonoltinib maleate inhibited Flt3 pathway signaling and cell cycle progression and induced apoptosis in acute myeloid leukemia cells harboring a FLT3-ITD in culture (PMID: 35256594). | 35256594 |
| 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 | 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 | 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 | 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 | Cytarabine + Idarubicin + Midostaurin | Guideline | Actionable | Rydapt (midostaurin) in combination with Idamycin (idarubicin) and Cytosar-U (cytarabine) is included in guidelines (category 1) 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 | Ponatinib | Phase I | Actionable | In a Phase I trial, Iclusig (ponatinib) resulted in a 25% (3/12) overall response rate, indicated as partial remission or better, in acute myeloid leukemia patients harboring FLT3-ITD (PMID: 23691988). | 23691988 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Ponatinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Iclusig (ponatinib) inhibited viability of patient derived acute myeloid leukemia cells harboring FLT3 ITD mutations in culture, and inhibited growth of tumors in cell line xenograft models (PMID: 21482694). | 21482694 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | 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 | 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 | 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 | 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 | 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 | 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 | 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 exon14 | acute myeloid leukemia | sensitive | Midostaurin | Guideline | Actionable | Rydapt (midostaurin) is included in guidelines as maintenance therapy for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org). | detail... |
| FLT3 exon14 | acute myeloid leukemia | sensitive | Cytarabine + 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 mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org). | detail... |
| FLT3 exon14 | acute myeloid leukemia | sensitive | Cytarabine + Daunorubicin + Midostaurin | Guideline | Actionable | Rydapt (midostaurin), in combination with Cerubidine (daunorubicin) and Cytosar-U (cytarabine), is included in guidelines as first-line treatment for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (PMID: 32171751; ESMO.org). | 32171751 detail... |
| FLT3 exon14 | acute myeloid leukemia | sensitive | Cytarabine + Daunorubicin + Midostaurin | Guideline | Actionable | Rydapt (midostaurin), in combination with Cerubidine (daunorubicin) and Cytosar-U (cytarabine), is included in guidelines for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org). | detail... |
| FLT3 exon14 | acute myeloid leukemia | sensitive | Gilteritinib | Guideline | Actionable | Xospata (gilteritinib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org). | detail... |
| FLT3 exon14 | acute myeloid leukemia | sensitive | Gilteritinib | Guideline | Actionable | Xospata (gilteritinib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (PMID: 32171751; ESMO.org). | detail... 32171751 |
| FLT3 exon14 | acute myeloid leukemia | sensitive | Cytarabine + Idarubicin + Midostaurin | Guideline | Actionable | Rydapt (midostaurin) in combination with Idamycin (idarubicin) and Cytosar-U (cytarabine) is included in guidelines for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org). | detail... |
| FLT3 mutant | acute myeloid leukemia | sensitive | Azacitidine + Venetoclax | Guideline | Actionable | Venclexta (venetoclax) in combination with Vidaza (azacitidine) is included in guidelines for adult patients with acute myeloid leukemia harboring a FLT3 mutation (NCCN.org). | detail... |
| FLT3 mutant | acute myeloid leukemia | sensitive | Selinexor + Sorafenib | Phase Ib/II | Actionable | In a Phase I/II trial, combination of Selinexor and Nexavar (sorafenib) treatment resulted in complete remission in 29% (4/14) and more than 50% blast reduction in 14% (2/14) of patients with acute myeloid leukemia harboring FLT3 ITD and/or D835 mutations (ASH, 59th Annual Meeting and Exposition, Dec 2017, Abstract 1344; NCT01607892). | detail... |
| FLT3 mutant | acute myeloid leukemia | sensitive | Azacitidine + Midostaurin | Phase Ib/II | Actionable | In a Phase Ib/II trial, acute myeloid leukemia patients harboring a FLT3 mutation demonstrated an improved remission duration when treated with the combination therapy, Rydapt (midostaurin) and Vidaza (azacitidine) (PMID: 25530214). | 25530214 |
| FLT3 mutant | acute myeloid leukemia | sensitive | Zotiraciclib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Zotiraciclib (TG02) inhibited growth of FLT3-mutated acute myeloid leukemia cells in culture, resulted in complete tumor regression in cell line xenograft animal models (PMID: 21860433). | 21860433 |
| FLT3 mutant | acute myeloid leukemia | sensitive | Crenolanib | Phase I | Actionable | In a Phase I trial, Crenolanib treatment resulted in complete response (CR) in 39% (7/18), partial response (PR) in 11% (2/18), and an overall survival (OS) of 234 days in AML patients harboring FLT3 mutations (D835X, ITD, or both) that received no prior therapy, and CR in 17% (6/36), PR in 14% (5/36), and OS of 94 days in those progressed on TKIs (J Clin Oncol 34, 2016 (suppl; abstr 7008)). | detail... |
| FLT3 mutant | acute myeloid leukemia | sensitive | E6201 | Preclinical | Actionable | In a preclinical study, acute myeloid leukemia cell lines harboring FLT3 mutations demonstrated increased sensitivity to E6201 induced growth inhibition and apoptosis in culture compared to FLT3 wild-type cells (PMID: 26822154). | 26822154 |
| FLT3 mutant | acute myeloid leukemia | sensitive | Gilteritinib | Phase Ib/II | Actionable | In a Phase I/II trial, treatment with Gilteritinib (ASP2215) resulted in an overall response rate of 49% (93/191) in patients with relapsed or refractory acute myeloid leukemia harboring FLT3 mutations, compared to 12% (7/58) in patients with wild-type FLT3 (PMID: 28645776; NCT02014558). | detail... 28645776 |
| FLT3 mutant | acute myeloid leukemia | sensitive | Gilteritinib | FDA approved - Has 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) compared to chemotherapy, resulted in superior 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%) in patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD), D835, or I836 mutation (PMID: 31665578; NCT02421939). | detail... detail... 31665578 |
| FLT3 mutant | acute myeloid leukemia | predicted - sensitive | ERAS-601 + Gilteritinib | Preclinical | Actionable | In a preclinical study, the combination of ERAS-601 and Xospata (gilteritinib) demonstrated synergy, resulting in decreased viability of acute myeloid leukemia cells harboring FLT3 mutations in culture and inhibition of tumor growth in in vivo models (Cancer Res (2022) 82 (12_Supplement): 3345). | detail... |
| FLT3 mutant | acute myeloid leukemia | sensitive | Cytarabine + Venetoclax | Phase Ib/II | Actionable | In a Phase I/II trial, Venclexta (venetoclax) in combination with low-dose cytarabine resulted in complete remission or complete remission with incomplete count recovery in 44% (7/16) of patients with acute myeloid leukemia harboring FLT3 mutations who were ineligible for intensive chemotherapy (ASH Annual Meeting, Dec 2018, Abstract 284; NCT02287233). | detail... |
| FLT3 mutant | acute myeloid leukemia | sensitive | Cytarabine + Venetoclax | Guideline | Actionable | Venclexta (venetoclax) in combination with Cytosar-U (cytarabine) is included in guidelines for adult patients with acute myeloid leukemia harboring a FLT3 mutation (NCCN.org). | detail... |
| FLT3 mutant | acute myeloid leukemia | sensitive | Decitabine + Venetoclax | Guideline | Actionable | Venclexta (venetoclax) in combination with Dacogen (decitabine) is included in guidelines for adult patients with acute myeloid leukemia harboring a FLT3 mutation (NCCN.org). | detail... |
| FLT3 mutant | acute myeloid leukemia | sensitive | Cytarabine + Daunorubicin + Midostaurin | Phase Ib/II | Actionable | In a Phase Ib clinical trial, Rydapt (midostaurin) treatment after Daunorubicin and Cytosar-U (cytarabine) induction resulted in complete remission in 92% (12/13) of acute myeloid leukemia patients carrying FLT3 mutations, although overall survival rate was similar to patients with wild-type FLT3 (PMID: 22627678). | 22627678 |
| FLT3 mutant | acute myeloid leukemia | sensitive | Cytarabine + Daunorubicin + Midostaurin | FDA approved - Has Companion Diagnostic | Actionable | In a Phase III trial that supported FDA approval, treatment with Rydapt (midostaurin), combined with Cytosar-U (cytarabine) and Daunorubicin, improved overall survival (HR=0.78, p=0.009) and event-free survival (HR=0.78, p=0.002) in patients with FLT3-mutant (ITD, D835X, and I836X mutations) acute myeloid leukemia compared to Cytosar-U (cytarabine) and Daunorubicin with placebo (PMID: 28644114; NCT00651261). | 28644114 detail... detail... |
| FLT3 mutant | acute myeloid leukemia | sensitive | UNC2025 | Preclinical | Actionable | In a preclinical study, UNC2025 inhibited FLT3 activation and growth of acute myeloid leukemia cells harboring a FLT3-ITD mutation in culture (PMID: 25068800). | 25068800 |
| FLT3 act mut | acute myeloid leukemia | sensitive | VS-5584 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, VS-5584 inhibited PI3K/mTOR signaling and cell proliferation in a FLT3-ITD positive human acute myeloid leukemia cell line in culture, and inhibited tumor growth in xenograft models (PMID: 23270925). | 23270925 |
| FLT3 act mut | acute myeloid leukemia | sensitive | 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 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 rate of 56% (5/9) in patients with tyrosine kinase domain mutations (PMID: 35849791; NCT03625505). | 35849791 |
| FLT3 act mut | acute myeloid leukemia | sensitive | Cytarabine + Daunorubicin + Sunitinib | Phase Ib/II | Actionable | In a Phase Ib/II trial, 59% (13/22) of acute myeloid leukemia patients harboring FLT3 activating mutations achieved complete remission following treatment with Sutent (sunitinib) in combination with Cytarabine and Daunorubicin (PMID: 25818407). | 25818407 |
| FLT3 act mut | acute myeloid leukemia | sensitive | Palbociclib + TCS 359 | Preclinical | Actionable | In a preclinical study, Ibrance (palbociclib) following TCS-359 treatment enhanced growth inhibition of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147). | 27099147 |
| FLT3 act mut | acute myeloid leukemia | sensitive | Palbociclib + SGI-1776 | Preclinical | Actionable | In a preclinical study, Ibrance (palbociclib) and SGI-1776 were synergistic towards growth inhibition of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147). | 27099147 |
| FLT3 act mut | acute myeloid leukemia | sensitive | TCS 359 | Preclinical | Actionable | In a preclinical study, TCS-359 inhibited growth of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147). | 27099147 |
| FLT3 act mut | acute myeloid leukemia | sensitive | Palbociclib + Quizartinib | Preclinical | Actionable | In a preclinical study, Ibrance (palbociclib) and Vanflyta (quizartinib) were synergistic towards growth inhibition of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147). | 27099147 |
| FLT3 act mut | acute myeloid leukemia | predicted - sensitive | Azacitidine + Glasdegib | Case Reports/Case Series | Emerging | In a Phase Ib trial, the combination of Daurismo (glasdegib) and Vidaza (azacitidine) resulted in an improved overall survival in acute myeloid leukemia patients harboring FLT3 mutations compared to those with wild-type FLT3 (P=0.039) (PMID: 35488900; NCT02367456). | 35488900 |
| FLT3 act mut | leukemia | sensitive | Pexidartinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX3397 inhibited FLT3 autophosphorylation in leukemia cells overexpressing FLT3 or harboring FLT3 activating mutations, and inhibited growth of leukemia cells harboring FLT3-ITD mutations in culture and in cell line xenograft models (ASH Annual Meeting Abstracts 2011 118: 3632). | detail... |
| FLT3 act mut | acute myeloid leukemia | predicted - sensitive | NMS-P088 | Phase I | Actionable | In a Phase I trial, NMS-P088 demonstrated manageable safety and preliminary efficacy with responses in 5 of 12 patients with acute myeloid leukemia harboring FLT3 mutations (Cancer Res (2023) 83 (8_Supplement): CT025; NCT03922100). | detail... |
| FLT3 act mut | acute myeloid leukemia | sensitive | Crenolanib | Phase II | Actionable | In a Phase II trial, relapsed or refractory acute myeloid leukemia patients harboring FLT3 activating mutations without a history of FLT3 therapy demonstrated a significantly greater overall survival and event free survival compared to those that had prior FLT3 therapy when treated with Crenolanib (ASH meeting, Dec 2014, abstract #389). | detail... |
| FLT3 act mut | acute myeloid leukemia | predicted - sensitive | BMF-500 | Preclinical | Actionable | In a preclinical study, BMF-500 inhibited Flt3 phosphorylation and downstream signaling and decreased viability of acute myeloid leukemia cell lines harboring FLT3 activating mutations in culture and induced tumor regression and improved survival in xenograft models (Blood (2022) 140 (Supplement 1): 6191-6192). | detail... |
| FLT3 act mut | acute myeloid leukemia | sensitive | Palbociclib | Preclinical | Actionable | In a preclinical study, Ibrance (palbociclib) blocked growth, induced apoptosis, and inhibited STAT activation in human FLT3-ITD positive human acute myeloid leukemia cells in culture (PMID: 27099147). | 27099147 |
| FLT3 act mut | acute myeloid leukemia | sensitive | Palbociclib + Tandutinib | Preclinical | Actionable | In a preclinical study, Ibrance (palbociclib) and tandutinib (MLN518) were synergistic towards growth inhibition of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147). | 27099147 |