Molecular Profile Detail

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Profile Name KIT K642E
Gene Variant Detail

KIT K642E (gain of function)

Relevant Treatment Approaches KIT Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
KIT K642E gastrointestinal stromal tumor sensitive KIT Inhibitor Regorafenib Preclinical - Cell culture Actionable In a preclinical study, Stivarga (regorafenib) inhibited proliferation of gastrointestinal stromal tumor cells harboring KIT K642E in culture (PMID: 21170960). 21170960
KIT K642E gastrointestinal stromal tumor sensitive KIT Inhibitor Ponatinib Preclinical Actionable In a preclinical study, a patient derived GIST cell line harboring KIT K642E demonstrated sensitivity to Iclusig (ponatinib) in culture (PMID: 25239608). 25239608
KIT K642E gastrointestinal stromal tumor sensitive KIT Inhibitor Imatinib + Infigratinib Preclinical - Cell culture Actionable In a preclinical study, Truseltiq (infigratinib) and Gleevec (imatinib) combination treatment demonstrated enhanced antiproliferative activity in gastrointestinal stromal tumor cells harboring KIT K642E in culture (PMID: 25673643). 25673643
KIT K642E vulvar melanoma predicted - sensitive KIT Inhibitor Imatinib Case Reports/Case Series Actionable In a clinical case study, Gleevec (imatinib) treatment resulted in partial response in a patient with recurrent vulval melanoma harboring KIT K642E, with reduction of tumor mass by 35% at 12 weeks (PMID: 20372153). 20372153
KIT K642E melanoma predicted - sensitive KIT Inhibitor Nilotinib Case Reports/Case Series Actionable In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41) including a melanoma patient harboring KIT K642E demonstrating a partial response and a progression free survival of 5.8 months and overall survival of 18.6 months (PMID: 28327988). 28327988
KIT K642E gastrointestinal stromal tumor sensitive KIT Inhibitor Axitinib Preclinical - Patient cell culture Actionable In a preclinical study, Inlyta (axitinib) inhibited phosphorylation of KIT and downstream signaling, reduced proliferation, and induced cell-cycle arrest in a cultured gastrointestinal stromal tumor (GIST) cell line harboring KIT K642E, and inhibited proliferation of primary GIST cells harboring KIT K642E in culture (PMID: 31205508). 31205508
KIT K642E gastrointestinal stromal tumor sensitive KIT Inhibitor Sunitinib Preclinical - Patient cell culture Actionable In a preclinical study, Sutent (sunitinib) inhibited proliferation of a gastrointestinal stromal tumor (GIST) cell line and primary GIST patient-derived cells harboring KIT K642E in culture (PMID: 31205508). 31205508
KIT K642E gastrointestinal stromal tumor sensitive Nintedanib Preclinical - Cell line xenograft Actionable In a preclinical study, Ofev (nintedanib) decreased Kit phosphorylation and downstream signaling, induced cell-cycle arrest and apoptosis, and inhibited proliferation of a gastrointestinal stromal tumor cell line and patient-derived cells harboring KIT K642E in culture, and suppressed tumor growth in cell line xenograft models (PMID: 35194937). 35194937
KIT K642E gastrointestinal stromal tumor predicted - sensitive KIT Inhibitor IDRX-42 Preclinical - Pdx Actionable In a preclinical study, IDRX-42 treatment inhibited mitosis and decreased tumor growth in a cell line xenograft model and a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT K642E (Cancer Res 2022;82(12_Suppl):Abstract nr 2666). detail...
KIT K642E melanoma predicted - sensitive KIT Inhibitor Imatinib Case Reports/Case Series Actionable In a Phase II trial, Gleevec (imatinib) treatment resulted in a durable objective response rate of 16% (4/25, 2 complete and 2 partial responses), a median time-to-progression of 12 weeks, and a median survival from treatment initiation of 46.3 weeks in patients with melanoma harboring KIT mutations, including 1 partial response, 1 transient partial response, and 2 stable disease in patients harboring KIT K642E (PMID: 21642685; NCT00470470). 21642685
KIT K642E mucosal melanoma predicted - sensitive KIT Inhibitor Imatinib Case Reports/Case Series Actionable In a Phase II trial, Gleevec (imatinib) treatment resulted in a best overall response rate of 53.8% (7/13, all partial responses) in patients with mucosal, acral, or chronically sun-damaged skin melanoma harboring KIT activating mutations in exons 11 (n=9), 13 (n=3), and 17 (n=1), including 1 partial response and 1 with stable disease in patients with mucosal melanoma harboring KIT K642E (n=3)(PMID: 23775962; NCT00424515). 23775962