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Therapy Name | Quizartinib |
Synonyms | |
Therapy Description |
Vanflyta (quizartinib) is a small molecule that selectively inhibits FLT3, which may induce apoptosis and inhibit tumor growth (PMID: 19654408, PMID: 23497317). Vanflyta (quizartinib) is FDA-approved for use in combination with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, in patients with newly diagnosed acute myeloid leukemia harboring FLT3 ITD mutations (FDA.gov). |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
---|---|---|---|---|
Quizartinib | Vanflyta | AC220 | FLT3 Inhibitor 69 | Vanflyta (quizartinib) is a small molecule that selectively inhibits FLT3, which may induce apoptosis and inhibit tumor growth (PMID: 19654408, PMID: 23497317). Vanflyta (quizartinib) is FDA-approved for use in combination with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, in patients with newly diagnosed acute myeloid leukemia harboring FLT3 ITD mutations (FDA.gov). |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FLT3 exon 14 ins FLT3 D835V | hematologic cancer | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 D835V were resistant to treatment with Vanflyta (quizartinib) in culture (PMID: 35395091). | 35395091 |
FLT3 exon 14 ins FLT3 D835V | hematologic cancer | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FLT3-ITD with FLT3 D835V were resistant to treatment with Vanflyta (quizartinib) in culture (PMID: 38231480). | 38231480 |
KIT D816V | acute myeloid leukemia | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) did not inhibit Kit phosphorylation or growth of erythroleukemia cells expressing KIT D816V in culture (PMID: 31309543). | 31309543 |
FLT3 exon 14 ins FLT3 D835del | hematologic cancer | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 D835del were resistant to treatment with Vanflyta (quizartinib) in culture (PMID: 35395091). | 35395091 |
FLT3 exon 14 ins FLT3 D835I | acute myeloid leukemia | predicted - resistant | Quizartinib | Case Reports/Case Series | Actionable | In a clinical case study, FLT3 D835I was identified as an acquired resistance mutation in a patient with acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD) whose disease progressed on Vanflyta (quizartinib) after an initial response (PMID: 27908881). | 27908881 |
KIT V560G KIT D816V | mast cell neoplasm | resistant | Quizartinib | Preclinical | Actionable | In a preclinical study, KIT D816V conferred resistance to Quizartinib in a mast cell line harboring both KIT V560G and KIT D816V in culture (PMID: 23497317). | 23497317 |
CBL Y371del FLT3 pos | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) inhibited proliferation of cells expressing wild-type FLT3 and CBL Y371del in culture (PMID: 31943762). | 31943762 |
FLT3 exon 14 ins FLT3 D835N | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835N in culture (PMID: 35395091). | 35395091 |
FLT3 E598_Y599del | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) inhibited Flt3 and Stat5 phosphorylation and viability in cells expressing FLT3 E598_Y599del in culture (PMID: 26012842). | 26012842 |
FLT3 exon 14 ins FLT3 D835Y | hematologic cancer | resistant | Quizartinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, cells expressing FLT3-ITD with FLT3 D835Y were resistant to treatment with Vanflyta (quizartinib) in culture and in a cell line xenograft model (PMID: 38231480). | 38231480 |
FLT3 exon 14 ins FLT3 D835Y | hematologic cancer | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 D835Y were resistant to treatment with Vanflyta (quizartinib) in culture (PMID: 35395091). | 35395091 |
FLT3 exon 14 ins FLT3 D835F | hematologic cancer | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 D835F were resistant to treatment with Vanflyta (quizartinib) in culture (PMID: 35395091). | 35395091 |
FLT3 D835A | hematologic cancer | no benefit | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) did not inhibit viability of transformed cells expressing FLT3 D835A in culture (PMID: 28077790). | 28077790 |
FLT3 exon 14 ins NRAS G12C | acute myeloid leukemia | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3-ITD mutation and expressing NRAS G12C demonstrated resistance to treatment with Vanflyta (quizartinib) in culture (PMID: 35395091). | 35395091 |
FLT3 exon 14 ins NRAS G12C | acute myeloid leukemia | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring FLT3-ITD and expressing NRAS G12C were resistant to Vanflyta (quizartinib) in culture (PMID: 38231480). | 38231480 |
FLT3 exon 14 ins FLT3 Y842C | acute myeloid leukemia | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring FLT3 ITD with FLT3 Y842C were resistant to Vanflyta (quizartinib) in culture (PMID: 32040554). | 32040554 |
CBL Y371H FLT3 wild-type | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) inhibited growth of transformed hematologic cells expressing CBL Y371H and wild-type FLT3 in culture (PMID: 31309543). | 31309543 |
FLT3 Q577_Y589delinsPSD | hematologic cancer | predicted - sensitive | Quizartinib | Preclinical - Biochemical | Actionable | In a preclinical study, Vanflyta (quizartinib) inhibited Flt3 phosphorylation in cells expressing FLT3 Q577_Y589delinsPSD in culture (PMID: 37246158). | 37246158 |
FLT3 exon 14 ins FLT3 A627P | hematologic cancer | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 A627P were resistant to treatment with Vanflyta (quizartinib) in culture (PMID: 22858906). | 22858906 |
FLT3 D835V | hematologic cancer | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, cultured cells expressing FLT3 D835V were resistant to treatment with Vanflyta (quizartinib) (PMID: 38231480). | 38231480 |
FLT3 exon 14 ins | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD in culture (PMID: 35395091). | 35395091 |
FLT3 exon 14 ins | hematologic cancer | sensitive | 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 FLT3 D698N | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D698N in culture (PMID: 35395091). | 35395091 |
FLT3 I836S | hematologic cancer | no benefit | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) did not inhibit viability of transformed cells expressing FLT3 I836S in culture (PMID: 28077790). | 28077790 |
FLT3 exon 14 ins FLT3 N841K | acute myeloid leukemia | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring FLT3 ITD with FLT3 N841K were resistant to Vanflyta (quizartinib) in culture (PMID: 32040554). | 32040554 |
FLT3 exon 14 ins FLT3 F691I | Advanced Solid Tumor | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and F691I were resistant to Vanflyta (quizartinib) in culture (PMID: 23392356). | 23392356 |
FLT3 exon 14 ins FLT3 G697R | hematologic cancer | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and FLT3 G697R were resistant to Vanflyta (quizartinib) in culture (PMID: 22875611). | 22875611 |
FLT3 Y599_D600insSTDNEYFYVDFREYEY | acute myeloid leukemia | predicted - sensitive | Quizartinib | Phase I | Actionable | In a Phase I clinical trial, patients with refractory or relapsed acute myeloid leukemia positive for FLT3-ITD demonstrated a 53% (9/17) response rate compared to a 14% (5/37) response rate in those patients negative for FLT3-ITD when treated with Vanflyta (quizartinib) (PMID: 24002496). | 24002496 |
FLT3 Y572del | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) decreased proliferation in transformed cells expressing FLT3 Y572del in culture (PMID: 33914060). | 33914060 |
FLT3 D835V | acute myeloid leukemia | decreased response | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, primary patient-derived acute myeloid leukemia blasts harboring FLT3 D835V were less sensitive to Vanflyta (quizartinib) in culture (PMID: 38231480). | 38231480 |
KIT D816V | Advanced Solid Tumor | resistant | Quizartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT D816V demonstrated resistance to Quizartinib in culture (PMID: 23497317). | 23497317 |
CBL Y371H FLT3 pos | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) inhibited proliferation of cells expressing wild-type FLT3 and CBL Y371H in culture (PMID: 31943762). | 31943762 |
FLT3 E598_Y599insFDFREYE FLT3 R845G | B-cell adult acute lymphocytic leukemia | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, B-cell acute lymphocytic leukemia cells harboring FLT3 R845G and FLT3 E598_Y599insFDFREYE were sensitive to treatment with Vanflyta (quizartinib), demonstrating decreased cell viability in culture (PMID: 30962949). | 30962949 |
FLT3 exon 14 ins FLT3 D835H | acute myeloid leukemia | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring FLT3 ITD with FLT3 D835H were resistant to Vanflyta (quizartinib) in culture (PMID: 32040554). | 32040554 |
FLT3 exon 14 ins FLT3 Y693N | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 Y693N in culture (PMID: 35395091). | 35395091 |
FLT3 S574del | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) decreased proliferation in transformed cells expressing FLT3 S574del in culture (PMID: 33914060). | 33914060 |
FLT3 exon 14 ins FLT3 Y693C | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 Y693C in culture (PMID: 35395091). | 35395091 |
FLT3 D835K FLT3 D835L | hematologic cancer | no benefit | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) did not inhibit viability of transformed cells expressing FLT3 D835L and D835K in culture (PMID: 28077790). | 28077790 |
FLT3 exon 14 ins FLT3 Y842C | hematologic cancer | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 Y842C were resistant to treatment with Vanflyta (quizartinib) in culture (PMID: 22858906). | 22858906 |
FLT3 exon 14 ins FLT3 Y842C | hematologic cancer | resistant | Quizartinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, cells expressing FLT3-ITD and FLT3 Y842C were resistant to treatment with Vanflyta (quizartinib) in culture and in a cell line xenograft model (PMID: 38231480). | 38231480 |
FLT3 exon 14 ins FLT3 D835A | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835A in culture (PMID: 35395091). | 35395091 |
FLT3 exon 14 ins FLT3 N676K | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 N676K in culture (PMID: 35395091). | 35395091 |
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 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 | 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 | Phase II | Actionable | In a Phase II trial, Vanflyta (quizartinib) treatment resulted in a composite complete remission (CCR) in 56% (63/112; 3 complete remission (CR)) of FLT3-ITD-positive patients vs. 36% (16/44; 1 CR) of FLT3-ITD-negative patients with relapsed/refractory acute myeloid leukemia (AML) after first-line therapy, and CCR in 46% (62/136; 5 CR) of FLT3-ITD-positive vs. 30% (12/40; 1 CR) in FLT3-ITD-negative patients with relapsed/refractory AML after salvage chemotherapy or transplant (PMID: 29859851; NCT00989261). | 29859851 |
FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Quizartinib | 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 | 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 JAK3 R953* | acute myeloid leukemia | predicted - resistant | Quizartinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with acute myeloid leukemia harboring a FLT3-ITD mutation treated with Vanflyta (quizartinib) was found to have acquired a JAK3 R953* mutation upon relapse (PMID: 33149267). | 33149267 |
FLT3 exon 14 ins FLT3 F621L | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 F621L were sensitive to treatment with Vanflyta (quizartinib), demonstrating growth inhibition in culture (PMID: 22858906). | 22858906 |
FLT3 I836T | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) inhibited viability in transformed cells expressing FLT3 I836T in culture (PMID: 28077790). | 28077790 |
FLT3 F590_D593delinsLY | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) inhibited Flt3 and Stat5 phosphorylation and viability in cells expressing FLT3 F590_D593delinsLY in culture (PMID: 26012842). | 26012842 |
FLT3 exon 14 ins FLT3 LOH | acute myeloid leukemia | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) inhibited proliferation of a acute myeloid leukemia cell line harboring a FLT3-ITD mutation with FLT3 loss of heterozygosity (LOH) (PMID: 28895560). | 28895560 |
FLT3 exon 14 ins FLT3 D835E | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835E in culture (PMID: 35395091). | 35395091 |
JAK3 V718L | esophagus adenocarcinoma | sensitive | Quizartinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) inhibited viability of cells derived from the brain metastases of a patient with esophagus adenocarcinoma harboring JAK3 V718L in culture (PMID: 38985431). | 38985431 |
FLT3 K614_G617del | hematologic cancer | predicted - sensitive | Quizartinib | Preclinical - Biochemical | Actionable | In a preclinical study, Vanflyta (quizartinib) inhibited Flt3 phosphorylation in cells expressing FLT3 K614_G617del in culture (PMID: 37246158). | 37246158 |
FLT3 exon 14 ins FLT3 A848P | Advanced Solid Tumor | decreased response | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and A848P demonstrated reduced sensitivity to Vanflyta (quizartinib) 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 Y842D | hematologic cancer | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, FLT3 Y842D was identified as a secondary mutation in transformed hematologic cells expressing FLT3-ITD that acquired resistance to Vanflyta (quizartinib) in culture (PMID: 25487917). | 25487917 |
FLT3 Q575del | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) decreased proliferation in transformed cells expressing FLT3 Q575del in culture (PMID: 33914060). | 33914060 |
FLT3 E573del | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) decreased proliferation in transformed cells expressing FLT3 E573del in culture (PMID: 33914060). | 33914060 |
FLT3 exon 14 ins FLT3 F691L FLT3 D835Y | hematologic cancer | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing FLT3-ITD, FLT3 F691L, and FLT3 D835Y demonstrated resistance to Vanflyta (quizartinib) in culture (PMID: 34768286). | 34768286 |
FLT3 Y842C | hematologic cancer | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, cultured cells expressing FLT3 Y842C were resistant to treatment with Vanflyta (quizartinib) (PMID: 38231480). | 38231480 |
CBL Q365_E366insSK FLT3 wild-type | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) inhibited growth of transformed hematologic cells expressing CBL Q365_E366insSK and wild-type FLT3 in culture (PMID: 31309543). | 31309543 |
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 D835H | hematologic cancer | predicted - resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 D835H were moderately resistant to treatment with Vanflyta (quizartinib) in culture (PMID: 35395091). | 35395091 |
FLT3 exon 14 ins FLT3 D835Y | acute myeloid leukemia | resistant | Quizartinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835Y demonstrated resistance to Vanflyta (quizartinib) treatment in culture (PMID: 27908881). | 27908881 |
FLT3 exon 14 ins FLT3 D835Y | acute myeloid leukemia | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, primary patient-derived acute myeloid leukemia blasts harboring FLT3-ITD with FLT3 D835Y were less sensitive to Vanflyta (quizartinib) in culture (PMID: 38231480). | 38231480 |
FLT3 exon 14 ins FLT3 D835Y | acute myeloid leukemia | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring FLT3 ITD with FLT3 D835Y were resistant to Vanflyta (quizartinib) in culture (PMID: 32040554). | 32040554 |
FLT3 exon 14 ins FLT3 N701K | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 N701K in culture (PMID: 33780043). | 33780043 |
FLT3 exon 14 ins FLT3 F691L FLT3 Y842H | hematologic cancer | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing FLT3-ITD, FLT3 F691L, and FLT3 Y842H demonstrated resistance to Vanflyta (quizartinib) in culture (PMID: 34768286). | 34768286 |
FLT3 exon 14 ins FLT3 Y842H | Advanced Solid Tumor | decreased response | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and Y842H demonstrated reduced sensitivity to Vanflyta (quizartinib) in culture (PMID: 23392356). | 23392356 |
FLT3 exon 14 ins IDH2 R140Q | acute myeloid leukemia | predicted - resistant | Quizartinib | Preclinical | Actionable | In a preclinical study, Vanflyta (quizartinib) failed to inhibit growth of cells isolated from a transgenic mouse model of acute myeloid leukemia harboring a FLT3-ITD mutation and IDH2 R140Q in culture (PMID: 33268594). | 33268594 |
FLT3 N676K | hematologic cancer | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, cultured cells expressing FLT3 N676K were resistant to treatment with Vanflyta (quizartinib) (PMID: 38231480). | 38231480 |
FLT3 exon 15 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, exon 15 insertion) (PMID: 37116523; NCT02668653). | detail... detail... 37116523 |
FLT3 exon 15 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 D586_D593delinsGG | hematologic cancer | predicted - sensitive | Quizartinib | Preclinical - Biochemical | Actionable | In a preclinical study, Vanflyta (quizartinib) inhibited Flt3 phosphorylation in cells expressing FLT3 D586_D593delinsGG in culture (PMID: 37246158). | 37246158 |
FLT3 exon 14 ins FLT3 D835V | acute myeloid leukemia | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring FLT3 ITD with FLT3 D835V were resistant to Vanflyta (quizartinib) in culture (PMID: 32040554). | 32040554 |
FLT3 exon 14 ins FLT3 D835V | acute myeloid leukemia | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, primary patient-derived acute myeloid leukemia blasts harboring FLT3-ITD with FLT3 D835V were less sensitive to Vanflyta (quizartinib) in culture (PMID: 38231480). | 38231480 |
FLT3 D835Y | hematologic cancer | conflicting | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, cultured cells expressing FLT3 D835Y were resistant to treatment with Vanflyta (quizartinib) (PMID: 38231480). | 38231480 |
FLT3 D835Y | hematologic cancer | conflicting | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) inhibited growth of transformed hematologic cells expressing FLT3 D835Y in culture (PMID: 31309543). | 31309543 |
FLT3 D835E | acute myeloid leukemia | decreased response | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, primary patient-derived acute myeloid leukemia blasts harboring FLT3 D835E were less sensitive to Vanflyta (quizartinib) in culture (PMID: 38231480). | 38231480 |
FLT3 exon 14 ins FLT3 N676D | Advanced Solid Tumor | decreased response | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and N676D demonstrated reduced sensitivity to Vanflyta (quizartinib) in culture (PMID: 23392356). | 23392356 |
FLT3 I836D FLT3 I836L | hematologic cancer | no benefit | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) did not inhibit viability of transformed cells expressing FLT3 I836D and I836L in culture (PMID: 28077790). | 28077790 |
FLT3 D835N | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) inhibited viability in transformed cells expressing FLT3 D835N in culture (PMID: 28077790). | 28077790 |
FLT3 exon 14 ins FLT3 K429E | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 K429E in culture (PMID: 35395091). | 35395091 |
KIT D816V | hematologic cancer | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) did not inhibit Kit phosphorylation or growth of transformed hematologic cells expressing KIT D816V in culture (PMID: 31309543). | 31309543 |
FLT3 exon 14 ins NRAS Q61K | acute myeloid leukemia | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3-ITD mutation and expressing NRAS Q61K demonstrated resistance to treatment with Vanflyta (quizartinib) in culture (PMID: 35395091). | 35395091 |
FLT3 D835G | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) inhibited viability in transformed cells expressing FLT3 D835G in culture (PMID: 28077790). | 28077790 |
FLT3 exon 14 ins FLT3 D835I | hematologic cancer | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 D835I were resistant to treatment with Vanflyta (quizartinib) in culture (PMID: 35395091). | 35395091 |
FLT3 exon 14 ins FLT3 D835G | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835G in culture (PMID: 35395091). | 35395091 |
CBL Q365_E366insSK FLT3 pos | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) inhibited proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). | 31943762 |
FLT3 S941_F942insRVS | hematologic cancer | predicted - sensitive | Quizartinib | Preclinical - Biochemical | Actionable | In a preclinical study, Vanflyta (quizartinib) inhibited Flt3 phosphorylation in cells expressing FLT3 S941_F942insRVS in culture (PMID: 37246158). | 37246158 |
FLT3 exon 14 ins FLT3 G697S | hematologic cancer | predicted - resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 G697S were moderately resistant to Vanflyta (quizartinib) treatment in culture (PMID: 35395091). | 35395091 |
FLT3 exon 14 ins FLT3 N676T | Advanced Solid Tumor | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing FLT3 ITD and FLT3 N676T were resistant to treatment with Vanflyta (quizartinib) in culture (Blood (2019) 134 (Supplement_1): 2672). | detail... |
FLT3 exon 14 ins FLT3 F691L FLT3 D835I | acute myeloid leukemia | predicted - resistant | Quizartinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) with FLT3 F691L and FLT3 D835I demonstrated resistance to Vanflyta (quizartinib) treatment in culture (PMID: 27908881). | 27908881 |
CBL mutant | bone marrow cancer | sensitive | Quizartinib | Preclinical | Actionable | In a preclinical study, Vanflyta (quizartinib) reduced white blood cell counts and decreased myeloid cell invasion in a CBL mutant mouse model with myeloproliferative disorder (PMID: 22990016). | 22990016 |
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 | 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 | 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 | 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 F590_D593delinsGP | hematologic cancer | predicted - sensitive | Quizartinib | Preclinical - Biochemical | Actionable | In a preclinical study, Vanflyta (quizartinib) inhibited Flt3 phosphorylation in cells expressing FLT3 F590_D593delinsGP in culture (PMID: 37246158). | 37246158 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT04047641 | Phase II | Quizartinib Cladribine + Cytarabine + Idarubicin + Quizartinib | Cladribine, Idarubicin, Cytarabine, and Quizartinib in Treating Patients With Newly Diagnosed, Relapsed, or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome | Recruiting | USA | 0 |
NCT03793478 | Phase Ib/II | Etoposide Cytarabine + Fludarabine + Methotrexate + Prednisolone + Quizartinib Cytarabine + Daunorubicin + Fludarabine + Methotrexate + Prednisolone + Quizartinib Cytarabine + Daunorubicin + Fludarabine + Hydrocortisone + Methotrexate + Quizartinib Cytarabine + Fludarabine + Methotrexate + Prednisolone Quizartinib | Safety and Efficacy of Quizartinib in Children and Young Adults With Acute Myeloid Leukemia (AML), a Cancer of the Blood | Active, not recruiting | USA | SWE | NLD | ITA | ISR | FRA | ESP | DNK | CAN | BEL | 0 |
NCT02039726 | Phase III | Cytarabine + Fludarabine Cytarabine + Etoposide + Mitoxantrone Quizartinib Filgrastim + Idarubicin | (QuANTUM-R): An Open-label Study of Quizartinib Monotherapy vs. Salvage Chemotherapy in Acute Myeloid Leukemia (AML) Subjects Who Are FLT3-ITD Positive | Completed | USA | POL | NLD | ITA | HUN | HRV | GBR | FRA | ESP | DEU | CZE | CAN | BEL | AUS | 5 |
NCT04107727 | Phase II | Cytarabine Cytarabine + Idarubicin Cytarabine + Idarubicin + Quizartinib Quizartinib Cytarabine + Quizartinib | Trial to Compare Efficacy and Safety of Chemotherapy/Quizartinib vs Chemotherapy/Placebo in Adults FMS-like Tyrosine Kinase 3 (FLT3) Wild-type Acute Myeloid Leukemia (AML) | Unknown status | ESP | 0 |