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KIT mutation is the driver behind most gastrointestinal stromal tumours, and the reason imatinib turned a sarcoma with a median survival of about a year into a chronic disease. This dossier gathers the 14 products (11 approved), 159 trials, 1 pathway 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.
Stem-cell factor receptor tyrosine kinase.
| 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.
| 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.
| Modality | Approved | Phase 3 |
|---|---|---|
| Small molecule 13 | ||
| Small-molecule BCR-ABL1 TKI 1 | - |
| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
| 3 | Active | A Multi-Center, Double-Blind, Randomized, Phase III Study to Investigate the Efficacy and Safety of Nofazinlimab (CS1003) in Combination With Lenvatinib Compared to Placebo in Combination With Lenvatinib as First-Line Therapy in Subjects With Advanced Hepatocellular Carcinoma (HCC) | - | ||
| 3 | Active | A Phase IIIb, Multi-center, Open-label, Randomized Study of Tolerability and Efficacy of Oral Asciminib Versus Nilotinib in Patients With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase. | - | ||
EMERALD-3 NCT05301842 | 3 | Positive | Embolisation-eligible unresectable HCC: STRIDE (durvalumab + tremelimumab) + lenvatinib + TACE vs TACE | PFS HR ~0.70 (interim); OS immature. | |
LITESPARK-011 NCT04586231 | 3 | Positive | Advanced clear-cell renal cell carcinoma that has progressed after anti-PD-1 or anti-PD-L1 therapy: belzutifan 120 mg plus lenvatinib 20 mg versus cabozantinib 60 mg, all oral once daily, open label, randomised 1:1 | Final progression-free survival 14.8 vs 10.7 months (hazard ratio 0.70, 95% CI 0.59 to 0.84; one-sided p<0.0001). Interim overall survival 34.9 vs 27.6 months (hazard ratio 0.85, 0.68 to 1.05; one-sided p 0.061), not statistically significant. Data cutoff 9 April 2025. | |
LITESPARK-012 NCT04736706 | 3 | Negative | Untreated advanced clear-cell RCC: pembrolizumab + lenvatinib ± belzutifan (or ± quavonlimab) | Primary endpoint not met (ASCO GU 2026). | |
| 3 | Active | A Phase III, Multi-center, Open-label, Randomized Study of Oral Asciminib Versus Investigator Selected TKI in Patients With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase | - | ||
| 3 | Active | A Randomized Phase III Trial Assessing a Regorafenib-irinotecan Combination (REGIRI) Versus Regorafenib Alone in Metastatic Colorectal Cancer Patients After Failure of Standard Therapies, According to the A/A Genotype of Cyclin D1 | - | ||
| 3 | Active | A Phase 3, Interventional, Randomized, Multicenter, Open-Label Study of Ripretinib vs Sunitinib in Patients With Advanced Gastrointestinal Stromal Tumor (GIST) After Treatment With Imatinib | - | ||
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%. | |
| 3 | Active | Multicenter, Single Arm Study of the Efficacy and Safety of Pexidartinib in Adult Subjects With Tenosynovial Giant Cell Tumor | - | ||
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. | |
| 3 | Active | A Phase III, Open Label, Randomised, Controlled, Multi-Centre Study To Assess the Efficacy and Safety of Savolitinib Versus Sunitinib in Patients With MET-Driven, Unresectable and Locally Advanced, Or Metastatic Papillary Renal Cell Carcinoma (PRCC) | - | ||
VOYAGER NCT03465722 | 3 | Negative | Third/fourth-line GIST: avapritinib vs regorafenib | PFS HR 1.25 (negative). | |
ENLIVEN NCT02371369 | 3 | Positive | Symptomatic tenosynovial giant cell tumour not amenable to surgery: pexidartinib versus placebo | Week 25 RECIST response 39% vs 0% (placebo); FDA approval 2019 with a liver-toxicity REMS. | |
IMblaze370 NCT02788279 | 3 | Negative | Previously treated metastatic colorectal adenocarcinoma, mostly microsatellite-stable: atezolizumab with cobimetinib, or atezolizumab alone, against regorafenib | Median overall survival 8.87 months with atezolizumab and cobimetinib against 8.51 months with regorafenib (hazard ratio 1.00). | |
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. | |
| 3 | Completed | A Randomized, Open-Label, Phase 3 Study to Evaluate Efficacy and Safety of Pembrolizumab (MK-3475) Plus Epacadostat vs Standard of Care (Sunitinib or Pazopanib) as First-Line Treatment for Locally Advanced or Metastatic Renal Cell Carcinoma (mRCC) (KEYNOTE-679/ECHO-302) | - | ||
TAPPAS NCT02979899 | 3 | Negative | Advanced angiosarcoma: pazopanib with or without the endoglin antibody TRC105 (carotuximab) | Adding TRC105 to pazopanib did not improve progression-free survival; stopped for futility. | |
CARMENA NCT00930033 | 3 | Positive | Metastatic clear cell renal cell carcinoma of intermediate or poor risk: cytoreductive nephrectomy followed by sunitinib against sunitinib alone | Sunitinib alone was non-inferior to cytoreductive nephrectomy plus sunitinib for overall survival in intermediate- and poor-risk metastatic clear cell renal cell carcinoma. | |
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. | |
CONCUR NCT01584830 | 3 | Positive | Asian patients with refractory metastatic colorectal cancer after at least two previous lines: regorafenib against placebo | Median overall survival 8.8 against 6.3 months (hazard ratio 0.55). | |
CORRECT NCT01103323 | 3 | Positive | Metastatic colorectal cancer progressing after all approved standard therapies: regorafenib 160 mg daily, three weeks on and one off, with best supportive care, against placebo | Median overall survival 6.4 against 5.0 months (hazard ratio 0.77); grade 3 or worse hand-foot skin reaction in 17 percent. |
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 →No companion diagnostic in the registry measures this target.
| 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. |
No open questions recorded for this target yet. Suggest one.
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.
The dossier as machine-readable JSON, at /api/v1/dossiers/kit.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-NC 4.0.