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FLT3 is a kinase mutated in about a third of acute myeloid leukaemias, where adding an inhibitor to chemotherapy improves survival. This dossier gathers the 6 products (5 approved), 15 trials, 2 pathways and 0 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
Class III receptor tyrosine kinase; ITD predicts shorter survival.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Acute myeloid leukaemia | 25-30% | FLT3-ITD or TKD | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
| Residue | Kind | How common | What it does | Addressed by | Defeats | Source |
|---|---|---|---|---|---|---|
| Internal tandem duplication (ITD) 572 to 603 | Activating | About 25% of AML | In-frame duplications in the juxtamembrane domain; high allelic ratio and long insertions carry worse prognosis. Every approved FLT3 inhibitor covers ITD. | - | Daver et al., Leukemia 2019 | |
| D835Y/V/H (TKD) 835 | Activating | About 7% of AML | Activation-loop mutation. Type I inhibitors (midostaurin, gilteritinib) cover it; type II quizartinib does not, and D835 emerges as resistance to quizartinib. | Daver et al., Leukemia 2019 | ||
| F691L (gatekeeper) 691 | Resistance | not sourced | Acquired after gilteritinib or quizartinib; reduces sensitivity to both classes. | none in corpus | Daver et al., Leukemia 2019 |
Frequencies are quoted from the source on each row; a blank means no figure was sourced, not that it is rare. Domain boundaries are approximate. Sources for the map: COSMIC: FLT3.
| Modality | Approved | Phase 2 |
|---|---|---|
| Small molecule 6 |
| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
| 3 | Completed | Phase 3 Open-label, Multicenter, Randomized Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FLT3 Mutation | - | ||
MORPHO NCT02997202 | 3 | Mixed | FLT3-ITD acute myeloid leukaemia in first remission after allogeneic transplant: gilteritinib 120 mg or placebo daily for 24 months as post-transplant maintenance, with measurable residual disease measured before and after transplant | Relapse-free survival hazard ratio 0.679 for gilteritinib against placebo, not statistically significant overall; in the prespecified MRD-positive half of patients the hazard ratio was 0.515, with no benefit in MRD-negative patients. | |
QuANTUM-First NCT02668653 | 3 | Positive | Newly diagnosed FLT3-ITD AML, age 18-75: quizartinib vs placebo with 7+3, consolidation, and up to 3 years of maintenance | OS 31.9 vs 15.1 months; HR 0.776. | |
ADMIRAL NCT02421939 | 3 | Positive | Relapsed or refractory FLT3-mutated AML: gilteritinib monotherapy vs salvage chemotherapy | OS 9.3 vs 5.6 months; HR 0.64. | |
RATIFY (CALGB 10603) NCT00651261 | 3 | Positive | Newly diagnosed FLT3-mutated AML, age 18-59: midostaurin vs placebo added to 7+3, consolidation, and one year of maintenance | Median OS 74.7 vs 25.6 months; HR 0.78. | |
| 3 | Recruiting | A Phase 3 Randomized Trial for Patients With De Novo AML Comparing Standard Therapy Including Gemtuzumab Ozogamicin (GO) to CPX-351 With GO, and the Addition of the FLT3 Inhibitor Gilteritinib for Patients With FLT3 Mutations | - | ||
Beat AML Master Trial NCT03013998 | platform | Recruiting | Newly diagnosed acute myeloid leukaemia in patients aged 60 and over: cytogenetic and genomic results returned within seven days assign each patient to a mutation-defined sub-study of targeted therapy, alone or with azacitidine or venetoclax | Genomic assignment within seven days was feasible; patients treated on Beat AML sub-studies had median overall survival of 12.8 months against 3.9 months for those choosing standard care (non-randomised comparison). | |
| 2 | Active | A Phase II, Open-label, Single Arm Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Twice Daily Midostaurin (PKC412) Combined With Standard Chemotherapy and as a Single Agent Post-consolidation Therapy in Children With Untreated FLT3-mutated AML | - | ||
| 2 | Recruiting | A Phase 2, Multicenter, Randomized, Open-label Trial to Evaluate Safety and Efficacy of Two Dose Levels of Quizartinib as Maintenance for Adult Patients With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia in Complete Remission | - | ||
| 2 | Recruiting | An Open Label, Phase 2 Clinical Trial of MEN1703 as Monotherapy and in Combination With Glofitamab in Patients With Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphoma | - | ||
| 2 | Recruiting | A Randomized Phase 2 Study of Pacritinib vs. Hydroxyurea in Patients With Advanced Proliferative Chronic Myelomonocytic Leukemia | - | ||
| 1/2 | Recruiting | A Phase 1/2, Open-Label, Dose-Escalation, Dose-Expansion Study of Enzomenib (DSP-5336) in Patients With Acute Leukemia and Other Selected Hematologic Malignancies, With and Without Mixed Lineage Leukemia (MLL) Rearrangement or Nucleophosmin 1 (NPM1) Mutation (Horizen-1) | - | ||
| 1/2 | Active | A Phase 1/2, Multicenter, Open-Label, Randomized Dose Ranging and Expansion Study of the Combination of Gilteritinib, Venetoclax and Azacitidine in Patients With Newly Diagnosed FLT3 Mutated Acute Myeloid Leukemia (AML) Not Eligible for Intensive Induction Chemotherapy | - | ||
| 1/2 | Active | A Phase 1b/2 Study of BMS-986158 Monotherapy and in Combination With Either Ruxolitinib or Fedratinib in Participants With DIPSS-Intermediate or High Risk Myelofibrosis | - | ||
| 1/2 | Active | A Phase 1/2, Multicenter, Dose-Escalating Study To Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy Of Quizartinib Administered in Combination With Re-Induction Chemotherapy, and as a Single-Agent Continuation Therapy, in Pediatric Relapsed/Refractory AML Subjects Aged 1 Month to <18 Years (and Young Adults Aged up to 21 Years) With FLT3-ITD Mutations | - |
No recorded escape route names this target.
KEGG's AML map shows the two hits that turn a normal blood stem cell into a leukaemia: a growth signal jammed on (FLT3, KIT or RAS) plus a broken maturation switch (fusion proteins such as PML-RARA or AML1-ETO, or mutated CEBPA and RUNX1). Drugs now exist for both halves.
Which nodes have drugs →In some leukaemias a broken chromatin protein (KMT2A, once called MLL) or a mutant NPM1 keeps embryonic growth genes (HOXA9, MEIS1) switched on, so blood cells never mature. Both need a partner called menin to stay on the DNA. Menin inhibitors pull the plug and the cells mature; the first was approved in 2024.
Which nodes have drugs →| Assay | Platform | Cut-off | Gates |
|---|---|---|---|
| LeukoStrat CDx FLT3 Mutation Assay Invivoscribe · FDA CDx 2017 | PCR | ITD signal ratio at least 0.05 or TKD mutation detected (midostaurin, gilteritinib); ITD only for quizartinib |
| Cell line | Identifiers | Why it is used |
|---|---|---|
| MOLM-13 | CVCL_2119 · ACH-000362 | ITD heterozygous. |
| MV4-11 | CVCL_0064 · ACH-000045 | ITD homozygous. |
| MOLM-14 | CVCL_7916 · ACH-001574 | ITD; sister line of MOLM-13. |
| Ba/F3 FLT3-ITD and D835Y | not resolved | Engineered alleles including F691L gatekeeper. |
No open questions recorded for this target yet. Suggest one.
Query for this target: (TITLE:"FLT3" OR ABSTRACT:"FLT3") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about FLT3, not a curated reading list.
The dossier as machine-readable JSON, at /api/v1/dossiers/flt3.json: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/flt3.json. Licence CC BY-NC 4.0.