KIT mutation is the driver behind most gastrointestinal stromal tumours, and the reason imatinib turned a lethal sarcoma into a chronic disease. This dossier gathers the 10 products (10 approved), 17 trials, 0 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.
Biology
Stem-cell factor receptor tyrosine kinase.
- GIST
- Mastocytosis
- Melanoma (mucosal/acral, rare)
Elsewhere: identifiers and databases
Built from HGNC, Ensembl, UniProt and ChEMBL idsHow common it is, by cancer
Full matrix →| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Sarcomas | 75-80% | GIST KIT mutation | PDGFRA in ~10% | Wikipedia |
| Melanoma | 2-3% | KIT mutation (acral/mucosal enriched) | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Mutation hotspots and which drugs address them
| Residue | Kind | How common | What it does | Addressed by | Defeats | Source |
|---|---|---|---|---|---|---|
| Exon 11 (W557_K558del, V559D, V560D, L576P) 557 to 576 | Activating | About two thirds of GIST | Juxtamembrane mutations release auto-inhibition; the most imatinib-sensitive group. | — | Corless et al., Nat Rev Cancer 2011 | |
| Exon 9 (A502_Y503dup) 502 to 503 | Activating | About 10% of GIST | Extracellular duplication; needs high-dose imatinib and responds better to sunitinib. | — | Corless et al., Nat Rev Cancer 2011 | |
| V654A / T670I (exons 13 to 14) 654 | Resistance | not sourced | ATP-binding-pocket secondary mutations after imatinib; sunitinib retains activity. | Corless et al., Nat Rev Cancer 2011 | ||
| D816V / N822K / A829P (exons 17 to 18) 816 | Resistance | not sourced | Activation-loop mutations: secondary resistance in GIST and the primary driver of systemic mastocytosis. Avapritinib and ripretinib were designed for the active conformation. | Corless et al., Nat Rev Cancer 2011 |
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: Cancer Hotspots (MSK) · COSMIC: KIT.
Products by modality and phase
Browse products →| Modality | Approved |
|---|---|
| Small molecule 9 | |
| Small-molecule BCR-ABL1 TKI 1 |
Trials
Evidence ranking →| Trial | Phase | Status | Setting | Result | Products |
|---|---|---|---|---|---|
| EMERALD-3 NCT05301842 | 3 | Positive | Embolisation-eligible unresectable HCC: STRIDE (durvalumab + tremelimumab) + lenvatinib + TACE vs TACE | PFS HR ~0.70 (interim); OS immature. | |
| INSIGHT NCT05734105 | 3 | Positive | Second-line GIST with KIT exon 11 + exon 17/18 mutations (ctDNA-selected): ripretinib vs sunitinib | PFS favouring ripretinib in the ctDNA-defined subgroup (2026). | |
| LITESPARK-012 NCT04736706 | 3 | Negative | Untreated advanced clear-cell RCC: pembrolizumab + lenvatinib ± belzutifan (or ± quavonlimab) | Primary endpoint not met (ASCO GU 2026). | |
| LEAP-012 NCT04246177 | 3 | Mixed | Unresectable non-metastatic HCC: TACE + lenvatinib + pembrolizumab vs TACE + placebo | PFS HR 0.66; final OS HR 0.98. | |
| PhALLCON NCT03589326 | 3 | Positive | Newly diagnosed Ph-positive ALL, adults: ponatinib vs imatinib, each with reduced-intensity chemotherapy | MRD-negative CR 34.4% vs 16.7%. | |
| LEAP-002 NCT03713593 | 3 | Negative | First-line unresectable HCC: lenvatinib + pembrolizumab vs lenvatinib | OS HR 0.84, not significant. | |
| CLEAR (KEYNOTE-581) NCT02811861 | 3 | Positive | Untreated advanced clear-cell RCC: lenvatinib + pembrolizumab vs sunitinib (and lenvatinib + everolimus arm) | PFS 23.9 vs 9.2 months (HR 0.39); OS HR 0.79. | |
| KEYNOTE-775 / Study 309 NCT03517449 | 3 | Positive | Advanced endometrial cancer after platinum: lenvatinib + pembrolizumab vs doxorubicin or weekly paclitaxel | OS 18.3 vs 11.4 months (HR 0.62). | |
| CheckMate 9ER NCT03141177 | 3 | Positive | Untreated advanced clear-cell RCC: nivolumab + cabozantinib vs sunitinib | PFS HR 0.51; OS HR 0.77 at ~4 years (46.5 vs 36.0 months). | |
| INVICTUS NCT03353753 | 3 | Positive | Advanced GIST after ≥3 kinase inhibitors: ripretinib vs placebo | PFS HR 0.15; OS HR 0.36. | |
| VOYAGER NCT03465722 | 3 | Negative | Third/fourth-line GIST: avapritinib vs regorafenib | PFS HR 1.25 (negative). | |
| KEYNOTE-426 NCT02853331 | 3 | Positive | Untreated advanced clear-cell RCC: pembrolizumab + axitinib vs sunitinib | OS HR 0.84 final (47.2 vs 40.8 months); PFS HR 0.69. | |
| CheckMate 214 NCT02231749 | 3 | Positive | Untreated advanced clear-cell RCC: nivolumab + ipilimumab vs sunitinib | 8-year OS HR 0.72 (ITT), 0.69 (intermediate/poor risk). | |
| REFLECT NCT01761266 | 3 | Positive | First-line unresectable HCC: lenvatinib vs sorafenib (non-inferiority) | OS 13.6 vs 12.3 months, non-inferior (HR 0.92). | |
| 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. | |
| RESORCE NCT01774344 | 3 | Positive | HCC progressing on sorafenib: regorafenib vs placebo | OS 10.6 vs 7.8 months, HR 0.63. | |
| SSGXVIII/AIO (adjuvant imatinib in GIST) NCT00116935 | 3 | Positive | High-risk resected GIST: adjuvant imatinib 3 years vs 1 year | RFS HR 0.46; OS HR 0.45 (5 years). |
Resistance routes that involve this target
Unaddressed routes →The resistance atlas has no route that names this target.
Pathways where it is a node
Pathway-to-drug matrix →No pathway diagram carries this target as a node.
Companion diagnostics and assays
Assay registry →No companion diagnostic in the registry measures this target.
Preclinical models
All models →| Cell line | Identifiers | Why it is used |
|---|---|---|
| GIST-T1 | CVCL_4976 · ACH-002332 | Exon 11 deletion. |
| GIST882 | CVCL_7044 | K642E. |
| GIST430 | CVCL_7040 | Exon 11 plus V654A. |
| GIST48 | CVCL_7041 | Exon 11 plus D820A. |
| HMC-1 | CVCL_0003 | Mast-cell leukaemia, D816V (HMC-1.2) and V560G; the mastocytosis line. |
| Kasumi-1 | CVCL_0589 · ACH-000263 | AML, N822K. |
- Kit V558del knock-in (Endogenous exon 11 deletion) Mouse Tumor Biology database (JAX)
Open questions
All open questions →No open questions recorded for this target yet. Suggest one.
Ideas and companies
Key papers and the live literature
Preprints →Query for this target: (TITLE:"KIT" OR ABSTRACT:"KIT") 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 KIT, not a curated reading list.
Export
The dossier as machine-readable 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/kit.json. Licence CC BY 4.0.