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| Gene | KIT |
| Variant | exon9 |
| Impact List | unknown |
| Protein Effect | unknown |
| Gene Variant Descriptions | KIT exon 9 (amino acids 449-514) indicates an unspecified mutation has occurred in exon 9 of the KIT gene. |
| Associated Drug Resistance | |
| Category Variants Paths |
KIT mutant KIT exon9 |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| KIT exon9 | gastrointestinal stromal tumor | sensitive | Imatinib | Guideline | Actionable | Gleevec (imatinib) is included in guidelines for gastrointestinal stromal tumor (GIST) patients harboring sensitizing mutations, such as KIT exon 9 mutations, as adjuvant therapy for patients with localized disease and as first-line therapy for patients with locally advanced, unresectable, or metastatic disease (PMID: 34560242; ESMO.org). | 34560242 detail... |
| KIT exon9 | gastrointestinal stromal tumor | sensitive | Imatinib | Guideline | Actionable | Gleevec (imatinib) is included in guidelines for patients with gastrointestinal stromal tumor (GIST) harboring KIT exon 9 mutations (NCCN.org). | detail... |
| KIT exon9 | Advanced Solid Tumor | resistant | Imatinib | Preclinical | Actionable | In a preclinical study, Gleevec (imatinib) had no effect on transformed cells expressing a KIT exon 9 mutation in culture (PMID: 25239608). | 25239608 |
| KIT exon9 | gastrointestinal stromal tumor | no benefit | Ponatinib | Phase II | Actionable | In a Phase II trial, Iclusig (ponatinib) treatment did not result in clinical benefit in gastrointestinal stromal tumor patients with KIT exon 9 mutations who had failed prior tyrosine kinase inhibitor treatment (PMID: 35091442; NCT01874665). | 35091442 |
| KIT exon9 | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a KIT exon 9 mutation demonstrated sensitivity to treatment with Iclusig (ponatinib) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 |
| KIT exon9 | melanoma | predicted - sensitive | Regorafenib | Case Reports/Case Series | Actionable | In a Phase II trial, second or later-line Stivarga (regorafenib) treatment resulted in a disease control rate of 73.9% (17/23, 2 complete responses, 5 partial responses), an objective response rate of 30.4% (7/23), and median overall survival (mOS) of 21.5 months in patients with melanoma harboring KIT exon 9, 11, 13, or 17 mutations, and improved mOS in patients with non-exon 11 mutations compared to patients with exon 11 mutations (24.9 mo vs 18.3 mo, P=0.042) (PMID: 37741071; NCT02501551). | 37741071 |
| KIT exon9 | gastrointestinal stromal tumor | sensitive | Regorafenib | Guideline | Actionable | Stivarga (regorafenib) is included in guidelines as third-line or subsequent therapy for locally advanced, unresectable, or metastatic gastrointestinal stromal tumor (GIST) patients harboring sensitizing mutations, such as KIT exon 9 mutations (PMID: 34560242; ESMO.org). | 34560242 detail... |
| KIT exon9 | Advanced Solid Tumor | resistant | Regorafenib | Preclinical | Actionable | In a preclinical study, Stivarga (regorafineb) had no effect on transformed cells expressing a KIT exon 9 mutation in culture (PMID: 25239608). | 25239608 |
| KIT exon9 | gastrointestinal stromal tumor | sensitive | Sunitinib | Clinical Study - Cohort | Actionable | In a retrospective analysis, GIST patients with KIT exon 9 mutations showed improved progression-free survival (PFS), overall survival, and objective response rate (ORR) compared to patients with exon 11 mutations, with a median PFS of 12.3 months vs. 7.0 months, and an ORR of 19% (8/42) vs. 6% (9/143) following treatment with Sutent (sunitinib) (PMID: 26772734). | 26772734 |
| KIT exon9 | gastrointestinal stromal tumor | sensitive | Sunitinib | Guideline | Actionable | Sutent (sunitinib) is included in guidelines as second-line or subsequent therapy for locally advanced, unresectable, or metastatic gastrointestinal stromal tumor (GIST) patients harboring sensitizing mutations, such as KIT exon 9 mutations (PMID: 34560242; ESMO.org). | detail... 34560242 |
| KIT exon9 | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a KIT exon 9 mutation demonstrated sensitivity to treatment with Sutent (sunitinib) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 |
| KIT exon9 | gastrointestinal stromal tumor | no benefit | Imatinib + Infigratinib | Phase I | Actionable | In a Phase I trial, Truseltiq (infigratinib) and Gleevec (imatinib) combination therapy resulted in stable disease as best response in 58% (7/12) of patients with advanced gastrointestinal stromal tumor harboring KIT mutations in exon 9 (n=3), exon 11 (n=10), or other (n=3), however, the trial was discontinued due to toxicity concerns (PMID: 30101387). | 30101387 |
| KIT exon9 | gastrointestinal stromal tumor | sensitive | Ripretinib | Phase I | Actionable | In a Phase I trial, Qinlock (ripretinib) was well tolerated, resulted in an objective response in 11.3% (16/142, 16 partial responses) and stable disease in 61.3% (87/142) of patients with advanced gastrointestinal stromal tumor harboring KIT (n=135) or PDGFRA mutations (n=7), with a median progression-free survival of 5.6 months, 18.3% (26/142) of the patients harbored KIT exon 9 mutations (PMID: 32804590; NCT02571036). | 32804590 |
| KIT exon9 | gastrointestinal stromal tumor | sensitive | Ripretinib | Guideline | Actionable | Qinlock (ripretinib) is included in guidelines as fourth-line or subsequent therapy for locally advanced, unresectable, or metastatic gastrointestinal stromal tumor (GIST) patients harboring sensitizing mutations, such as KIT exon 9 mutations (PMID: 34560242; ESMO.org). | 34560242 detail... |
| KIT exon9 | gastrointestinal stromal tumor | predicted - sensitive | IDRX-42 | Phase I | Actionable | In a Phase I trial, IDRX-42 treatment demonstrated safety and resulted in 9 partial responses among 39 evaluable patients with gastrointestinal stromal tumors harboring a KIT exon 11 (n=27), exon 9 (n=13), or exon 8 (n=2) mutation with a clinical benefit rate of 71% overall and 100% as second-line treatment (J Clin Oncol 42, 2024 (suppl 16; abstr 11501); NCT05489237). | detail... |
| KIT exon9 | gastrointestinal stromal tumor | no benefit | Imatinib + Spartalizumab | Phase Ib/II | Actionable | In a Phase Ib/II trial, the combination of Spartalizumab (PDR001) and Gleevec (imatinib) was tolerable but demonstrated limited efficacy in Phase II, with an objective response rate of 0% (0/29), a disease control rate of 37.9% (11/29), median progression-free survival of 2.3 months, and overall survival of 9.5 months in patients with gastrointestinal stromal tumor harboring KIT exon 9 (n=8), exon 11 (n=17), or other mutations (PMID: 38662455). | 38662455 |