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Profile Name | KIT T632I |
Gene Variant Detail | |
Relevant Treatment Approaches |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
KIT mutant | melanoma | sensitive | Nilotinib | Phase II | Actionable | In a Phase II trial, Tasigna (nilotinib) treatment in patients with melanoma harboring KIT mutations resulted in an overall response rate of 26.2% (11/42), which included 11 patients with a partial response, a median duration of response of 7.1 months, and an overall survival of 18 months (PMID: 28327988; NCT01028222). | 28327988 |
KIT mutant | gastrointestinal stromal tumor | not applicable | N/A | Clinical Study | Diagnostic | KIT mutations are used in the diagnosis of gastrointestinal stromal tumors (PMID: 25193432, PMID: 26276366, PMID: 25729899). | 25193432 26276366 25729899 |
KIT mutant | gastrointestinal stromal tumor | sensitive | Imatinib + Infigratinib | Preclinical - Pdx | Actionable | In a preclinical study, Truseltiq (infigratinib) and Gleevec (imatinib) combination treatment demonstrated enhanced antitumor activity in patient derived xenograft models of gastrointestinal stromal tumor harboring KIT mutations (PMID: 25673643). | 25673643 |
KIT exon13 | gastrointestinal stromal tumor | sensitive | Imatinib + MK2206 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Gleevec (imatinib) and MK2206 demonstrated synergy in inhibiting growth of a gastrointestinal stromal tumor cell line harboring a KIT exon 13 mutation in culture (PMID: 27370604). | 27370604 |
KIT mutant | gastrointestinal stromal tumor | predicted - sensitive | Ripretinib | Phase I | Actionable | In a Phase I trial, Qinlock (ripretinib) demonstrated preliminary safety and efficacy in patients with advanced solid tumors, including KIT-mutant gastrointestinal stromal tumor (GIST), with 1 patient harboring KIT exon 11 and 17 mutations demonstrating a partial response, and 7/7 KIT-mutant GIST patients demonstrating a partial metabolic response (EORTC-NCI-AACR 2016, Abs 7LBA). | detail... |
KIT exon13 | melanoma | sensitive | Nilotinib | Phase II | Actionable | In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41), which included a partial response in 7.7% (1/13) of melanoma patients harboring KIT exon 13 mutations (PMID: 28327988). | 28327988 |
KIT mutant | melanoma | sensitive | Nilotinib | Phase II | Actionable | In a Phase II trial, Tasigna (nilotinib) treatment resulted in complete response in 4% (1/25), durable partial response in 16% (4/25), and stable disease in 56% (14/25) of melanoma patients harboring KIT mutations (PMID: 28843487; NCT01168050). | 28843487 |
KIT exon13 | melanoma | sensitive | Nilotinib | Phase II | Actionable | In a Phase II trial, Tasigna (nilotinib) treatment resulted in complete response in 5% (1/19) and partial response in 21% (4/19) of melanoma patients harboring KIT exon 11 or exon 13 mutations (PMID: 28843487; NCT01168050). | 28843487 |
KIT mutant | gastrointestinal stromal tumor | predicted - sensitive | Avapritinib | Phase I | Actionable | In a Phase I (NAVIGATOR) trial, Ayvakit (avapritinib) treatment resulted in an objective response rate of 13% (7/52, 7 partial responses) and a disease control rate of 63% (33/52) in patients with KIT-mutant gastrointestinal stromal tumor (The CTOS 2018 Annual Meeting, Nov 14-17, Rome Italy, Paper 012 3027631; NCT02508532). | detail... |
KIT mutant | gastrointestinal stromal tumor | predicted - 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 (exon 11, n=103; exon 9, n=26; other, n=6) or PDGFRA mutations (n=7), with a median progression-free survival of 5.6 months (PMID: 32804590; NCT02571036). | 32804590 |
KIT exon13 | gastrointestinal stromal tumor | sensitive | Adavosertib + Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Adavosertib (MK-1775) and Ayvakit (avapritinib) synergized to inhibit growth of a gastrointestinal stromal tumor cell line harboring a KIT exon 13 mutation in culture (PMID: 33320833). | 33320833 |
KIT mutant | melanoma | predicted - sensitive | Ripretinib | Phase I | Actionable | In a Phase I trial, Qinlock (ripretinib) treatment demonstrated manageable safety and preliminary efficacy in patients with KIT-mutated melanoma, and led to an objective response rate of 23% (6/26, 1 complete and 5 partial responses), a median progression-free survival of 7.3 months, and a median duration of response of 9.1 months (PMID: 35753087; NCT02571036). | 35753087 |
KIT exon13 | melanoma | not predictive | Pembrolizumab | Clinical Study | Actionable | In a retrospective analysis, real-world treatment with either Keytruda (pembrolizumab) or Toripalimab (JS001) resulted in a median disease-free survival of 33 months in melanoma patients harboring KIT mutations in either exon 11 (64.8%), exon 13 (17.6%), or exon 17 (17.6%) compared to 32 months in patients with wild-type BRAF, NRAS, and KIT (p=0.200) (PMID: 37403699). | 37403699 |
KIT exon13 | melanoma | not predictive | Toripalimab-tpzi | Clinical Study | Actionable | In a retrospective analysis, real-world treatment with either Keytruda (pembrolizumab) or Loqtorz (toripalimab-tpzi) resulted in a median disease-free survival of 33 months in melanoma patients harboring KIT mutations in either exon 11 (64.8%), exon 13 (17.6%), or exon 17 (17.6%) compared to 32 months in patients with wild-type BRAF, NRAS, and KIT (p=0.200) (PMID: 37403699). | 37403699 |
KIT exon13 | melanoma | 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 |