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Profile Name KIT L576P
Gene Variant Detail

KIT L576P (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 L576P melanoma predicted - sensitive KIT Inhibitor Bevacizumab + Sorafenib Case Reports/Case Series Actionable In a Phase I trial, a melanoma patient harboring KIT L576P demonstrated sensitivity to the combination treatment of Nexavar (sorafenib) and Avastin (bevacizumab), resulting in a partial response for 8 months (PMID: 25363205). 25363205
KIT L576P melanoma sensitive KIT Inhibitor Dasatinib Case Reports/Case Series Actionable In a clinical study, two patients with melanoma harboring KIT L576P, one who had progressed on Gleevec (imatinib), demonstrated initial clinical benefit following treatment with Sprycel (dasatinib); however, one patient progressed after 3 months, and the other patient progressed after 4 months of treatment (PMID: 19671763). 19671763
KIT L576P melanoma predicted - sensitive KIT Inhibitor Imatinib Case Reports/Case Series Actionable In a clinical case study, Gleevec (imatinib) treatment resulted in a 42% reduction of target lesions and an improvement of symptoms in a patient with metastasized labial melanoma harboring KIT L576P (PMID: 20372153). 20372153
KIT L576P 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 three melanoma patients harboring KIT L576P demonstrating a partial response (PMID: 28327988). 28327988
KIT L576P melanoma sensitive KIT Inhibitor Dasatinib Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) inhibited MNK pathway activation and proliferation of melanoma cell lines harboring KIT L576P in culture (PMID: 29035277). 29035277
KIT L576P melanoma sensitive SEL201 Preclinical - Cell line xenograft Actionable In a preclinical study, SEL201 inhibited MNK pathway signaling and growth of melanoma cells harboring KIT L576P in culture, and suppressed tumor metastasis in xenograft models (PMID: 29035277). 29035277
KIT L576P Advanced Solid Tumor sensitive KIT Inhibitor Axitinib Preclinical - Cell culture Actionable In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and proliferation of transformed cells expressing KIT L576P in culture (PMID: 31205508). 31205508
KIT L576P Advanced Solid Tumor sensitive Nintedanib Preclinical - Cell culture Actionable In a preclinical study, Ofev (nintedanib) inhibited Kit autophosphorylation and proliferation of transformed cells expressing KIT L576P in culture (PMID: 35194937). 35194937
KIT L576P Advanced Solid Tumor sensitive KIT Inhibitor Imatinib Preclinical - Cell culture Actionable In a preclinical study, Gleevec (imatinib) inhibited proliferation of transformed cells expressing KIT L576P in culture (PMID: 35194937). 35194937
KIT L576P Advanced Solid Tumor sensitive KIT Inhibitor Sunitinib Preclinical - Cell culture Actionable In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT L576P in culture (PMID: 35194937). 35194937
KIT L576P melanoma predicted - sensitive KIT Inhibitor Ripretinib Case Reports/Case Series Actionable In a Phase I trial, Qinlock (ripretinib) treatment resulted in a partial response in 3 of 4 patients with metastatic melanoma harboring KIT L576P (PMID: 35753087; NCT02571036). 35753087
KIT L576P 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 2 complete, 1 partial, 1 transient partial response, and 1 stable disease in patients harboring KIT L576P (n=7) (PMID: 21642685; NCT00470470). 21642685
KIT L576P 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 3 partial responses and 1 with stable disease in patients with melanoma harboring KIT L576P (PMID: 23775962; NCT00424515). 23775962
KIT L576P acral lentiginous melanoma predicted - sensitive KIT Inhibitor Nilotinib Case Reports/Case Series Actionable In a Phase II trial, Tasigna (nilotinib) treatment resulted in an overall response rate of 16.7% (7/42, 1 complete and 6 partial responses) and a disease control rate of 57.1% in melanoma patients harboring KIT mutations (n=25), amplification (n=15), or both (n=2), including 1 complete and 2 partial responses in patients with acral melanoma harboring KIT L576P (n=4) (PMID: 26424760; NCT01099514). 26424760