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Gene KIT
Variant V654A
Impact List missense
Protein Effect unknown
Gene Variant Descriptions KIT V654A lies within the protein kinase domain (exon 13) of the Kit protein (UniProt.org). V654A has been described as a secondary drug resistance mutation (PMID: 17363509, PMID: 16751810), but has conflicting functional data, as in some studies, results in increased proliferation in cultured cells and in murine cells (corresponding to V653A), leads to increased proliferation and elevated Stat activation in the context of KIT V559del (corresponding to V558del in mouse) in culture (PMID: 33024275), is constitutively phosphorylated in culture (PMID: 27440273), but in another study is not transforming and does not result in constitutive activation (PMID: 17363509), and therefore, its effect on Kit protein function is unknown.
Associated Drug Resistance Y

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Transcript NM_000222.2
gDNA chr4:g.54728092T>C
cDNA c.1961T>C
Protein p.V654A
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_000222 chr4:g.54728092T>C c.1961T>C p.V654A RefSeq GRCh38/hg38
NM_000222.2 chr4:g.54728092T>C c.1961T>C p.V654A RefSeq GRCh38/hg38
XM_017008178.1 chr4:g.54728092T>C c.1961T>C p.V654A RefSeq GRCh38/hg38
XM_017008178 chr4:g.54728092T>C c.1961T>C p.V654A RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
KIT V654A Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, cells expressing KIT V654A demonstrated some sensitivity to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT V654A Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT V654A in culture (PMID: 35194937). 35194937
KIT V654A Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT V654A in culture (PMID: 31205508). 31205508
KIT V654A Advanced Solid Tumor sensitive Nintedanib Preclinical - Cell culture Actionable In a preclinical study, Ofev (nintedanib) inhibited proliferation of transformed cells expressing KIT V654A in culture (PMID: 35194937). 35194937
KIT V654A Advanced Solid Tumor sensitive Axitinib Preclinical - Cell line xenograft Actionable In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and proliferation of transformed cells expressing KIT V654A in culture, and inhibited tumor growth in xenograft models (PMID: 31205508). 31205508
KIT V654A Advanced Solid Tumor resistant Imatinib Preclinical Actionable In a preclinical study, cells expressing KIT V654A demonstrated resistance to Gleevec (imatinib) in culture (PMID: 16751810). 16751810
KIT V654A gastrointestinal stromal tumor predicted - resistant Avapritinib Phase I Actionable In a Phase I trial, patients with gastrointestinal stromal tumors harboring either KIT V654A or KIT T670I demonstrated decreased overall response rate (0%, 0/25 vs. 26%, 22/84) and increased progressive disease rate (72% vs 23%) compared to those without either KIT mutation when treated with Ayvakit (avapritinib) (PMID: 31270078; NCT02508532). 31270078
KIT W557_K558del KIT V654A Advanced Solid Tumor resistant Ripretinib Preclinical - Cell culture Actionable In a preclinical study, Qinlock (ripretinib) failed to reduce cell viability and inhibit KIT signaling in transformed cells expressing KIT W557_K558del and KIT V654A in culture (PMID: 32350132). 32350132
KIT W557_K558del KIT V654A gastrointestinal stromal tumor sensitive AZD3229 Preclinical - Pdx Actionable In a preclinical study, AZD3229 inhibited Kit signaling and tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT W557_K558del and KIT V654A, which was established from a patient who did not respond to Gleevec (imatinib) treatment (PMID: 32350132). 32350132
KIT W557_K558del KIT V654A Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT V654A demonstrated sensitivity to treatment with Sutent (sunitinib) in both culture and cell line xenograft models, resulting in reduced cell viability, decreased tumor volume, and tumor regression (PMID: 25239608). 25239608
KIT W557_K558del KIT V654A Advanced Solid Tumor sensitive Ponatinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT V654A demonstrated sensitivity to treatment with Iclusig (ponatinib) in both culture and cell line xenograft models, resulting in reduced cell viability and decreased tumor volume (PMID: 25239608). 25239608
KIT W557_K558del KIT V654A gastrointestinal stromal tumor sensitive Sunitinib Preclinical - Pdx Actionable In a preclinical study, Sutent (sunitinib) inhibited tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT W557_K558del and KIT V654A, which was established from a patient who did not respond to Gleevec (imatinib) treatment (PMID: 32350132). 32350132
KIT W557_K558del KIT V654A Advanced Solid Tumor no benefit Imatinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT V654A demonstrated no response to treatment with Gleevec (imatinib) in both culture and xenograft models (PMID: 25239608). 25239608
KIT W557_K558del KIT V654A Advanced Solid Tumor resistant Regorafenib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT V654A demonstrated resistance to treatment with Stivarga (regorafenib) in culture (PMID: 25239608). 25239608
KIT W557_K558del KIT V654A gastrointestinal stromal tumor sensitive Avapritinib Preclinical - Pdx Actionable In a preclinical study, Ayvakit (avapritinib) inhibited Kit phosphorylation and resulted in tumor regression in patient-derived xenograft models of Gleevec (imatinib)-resistant gastrointestinal stromal tumor harboring KIT W557_K558del and V654A (PMID: 29093181). 29093181
KIT W557_K558del KIT V654A Advanced Solid Tumor sensitive AZD3229 Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells expressing KIT W557_K558del and KIT V654A demonstrated sensitivity to treatment with AZD3229 in both culture and cell line xenograft models, resulting in reduced cell viability, decreased KIT signaling, and tumor regression (PMID: 32350132). 32350132
KIT W557_K558del KIT V654A Advanced Solid Tumor resistant Avapritinib Preclinical - Cell line xenograft Actionable In a preclinical study, Ayvakit (avapritinib) failed to inhibit cell growth or KIT signaling in culture and did not suppress tumor growth in cell line xenograft models of transformed cells expressing KIT W557_K558del and KIT V654A (PMID: 32350132). 32350132
KIT V560_L576del KIT V654A gastrointestinal stromal tumor sensitive HQP1351 Preclinical - Cell line xenograft Actionable In a preclinical study, HQP1351 treatment inhibited Kit downstream signalling, resulted in cell cycle arrest and apoptosis in a Gleevec (imatinib)-resistant gastrointestinal stromal tumor (GIST) cell line harboring KIT V560_L576del and V654A in culture, and inhibited tumor growth in a cell line xenograft model (PMID: 31673329). 31673329
KIT V560_L576del KIT V654A gastrointestinal stromal tumor sensitive Sunitinib Preclinical Actionable In a preclinical study, a patient derived GIST cell line co-harboring KIT V560_L576del and KIT V654A demonstrated sensitivity to treatment with Sutent (sunitinib) (PMID: 25239608). 25239608
KIT V560_L576del KIT V654A gastrointestinal stromal tumor sensitive Sunitinib Preclinical - Pdx Actionable In a preclinical study, Sutent (sunitinib) inhibited tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT V560_L576del and V654A with overexpression of GPR20 (IHC score 3+) (PMID: 33579785). 33579785
KIT V560_L576del KIT V654A gastrointestinal stromal tumor resistant Imatinib Preclinical - Pdx Actionable In a preclinical study, a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT V560_L576del and V654A with overexpression of GPR20 (IHC score 3+) demonstrated resistance to treatment with Gleevec (imatinib) (PMID: 33579785). 33579785
KIT V560_L576del KIT V654A gastrointestinal stromal tumor sensitive Regorafenib Preclinical - Pdx Actionable In a preclinical study, Stivarga (regorafenib) inhibited tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT V560_L576del and V654A with overexpression of GPR20 (IHC score 3+) (PMID: 33579785). 33579785
KIT exon11 KIT V654A gastrointestinal stromal tumor sensitive Copanlisib Preclinical - Cell culture Actionable In a preclinical study, Aliqopa (copanlisib) inhibited cell growth and PI3K signaling in a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and KIT V654A in culture (PMID: 32371592). 32371592
KIT exon11 KIT V654A 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 Gleevec (imatinib)-resistant gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion mutation and KIT V654A in culture (PMID: 27370604). 27370604
KIT exon11 KIT V654A gastrointestinal stromal tumor predicted - sensitive Copanlisib + Imatinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Aliqopa (copanlisib) and Gleevec (imatinib) demonstrated enhanced cell growth inhibition but did not result in increased apoptosis of gastrointestinal stromal tumor cells harboring a KIT exon 11 deletion and KIT V654A compared to either agent alone in culture (PMID: 32371592). 32371592
KIT V560D KIT V654A Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT V560D and KIT V654A demonstrated sensitivity to Sutent (sunitinib) in culture, resulting in reduced cell viability (PMID: 32350132). 32350132
KIT V560D KIT V654A Advanced Solid Tumor resistant Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT V560D and KIT V654A were resistant to Flumatinib in culture (PMID: 24205792). 24205792
KIT V560D KIT V654A Advanced Solid Tumor sensitive AZD3229 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT V560D and KIT V654A demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). 32350132
KIT V560D KIT V654A Advanced Solid Tumor sensitive Motesanib Diphosphate Preclinical - Cell culture Actionable In a preclinical study, Motesanib (AMG 706) inhibited KIT phosphorylation and growth of cells expressing a KIT V560D/V654A double mutation in culture (PMID: 20633291). 20633291
KIT V560D KIT V654A Advanced Solid Tumor decreased response Ripretinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT V560D and KIT V654A demonstrated a decreased response to treatment with Qinlock (ripretinib) compared to cells expressing KIT V560D alone in culture (PMID: 32350132). 32350132
KIT V560D KIT V654A Advanced Solid Tumor resistant Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT V560D and KIT V654A demonstrated resistance to Gleevec (imatinib) in culture (PMID: 32350132). 32350132
KIT V560D KIT V654A Advanced Solid Tumor resistant Regorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT V560D and KIT V654A demonstrated resistance to treatment with Stivarga (regorafenib) in culture (PMID: 32350132). 32350132
KIT V560D KIT V654A Advanced Solid Tumor decreased response Avapritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT V560D and KIT V654A demonstrated a decreased response to treatment with Ayvakit (avapritinib) compared to cells expressing KIT V560D alone in culture (PMID: 31270078). 31270078
KIT V560del KIT V654A Advanced Solid Tumor sensitive Nilotinib Preclinical - Cell culture Actionable In a preclinical study, Tasigna (nilotinib) inhibited proliferation of transformed cells expressing a KIT V560del/V654A double mutation in culture (PMID: 17699867). 17699867
KIT V559D KIT V654A Advanced Solid Tumor resistant Ripretinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT V559D and V654A were resistant to Qinlock (ripretinib) treatment in culture (PMID: 35194937). 35194937
KIT V559D KIT V654A Advanced Solid Tumor sensitive Axitinib Preclinical - Cell culture Actionable In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and proliferation of transformed cells expressing KIT V654A and KIT V559D in culture (PMID: 31205508). 31205508
KIT V559D KIT V654A Advanced Solid Tumor resistant Avapritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT V559D and V654A were resistant to Ayvakit (avapritinib) treatment in culture (PMID: 35194937). 35194937
KIT V559D KIT V654A Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT V559D and V654A in culture (PMID: 35194937). 35194937
KIT V559D KIT V654A Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT V559D and KIT V654A were sensitive to treatment with Sutent (sunitinib) in culture, demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT V559D KIT V654A Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT V654A and KIT V559D in culture (PMID: 31205508). 31205508
KIT V559D KIT V654A Advanced Solid Tumor predicted - sensitive Nintedanib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT V559D and V654A demonstrated decreased proliferation in response to Ofev (nintedanib) in culture, but were less sensitive to treatment compared to cells expressing either KIT V559D or KIT V654A alone (PMID: 35194937). 35194937
KIT K558_V560del KIT V654A gastrointestinal stromal tumor predicted - resistant Imatinib Case Reports/Case Series Actionable In a clinical study, KIT V654A was identified as a secondary mutation in a patient with gastrointestinal stromal tumor harboring a primary KIT K558_V560del mutation, who developed resistance to Gleevec (imatinib) (PMID: 18488160). 18488160
KIT V569_L576del KIT V654A KIT N822K gastrointestinal stromal tumor predicted - resistant Imatinib Case Reports/Case Series Actionable In a clinical study, KIT V654A and KIT N822K were identified as secondary mutations in a patient with gastrointestinal stromal tumor harboring a primary KIT V569_L576del mutation, who developed resistance to Gleevec (imatinib) (PMID: 18488160). 18488160
KIT V654A KIT D816V Advanced Solid Tumor resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT D816V and KIT V654A demonstrated resistance to treatment with Rydapt (midostaurin) in culture compared to cells expressing KIT D816V alone (PMID: 31270078). 31270078
KIT V654A KIT D816V Advanced Solid Tumor predicted - sensitive Avapritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT D816V and KIT V654A demonstrated some sensitivity to treatment with Ayvakit (avapritinib) in culture (PMID: 31270078). 31270078
KIT V559_G565del KIT V654A KIT A829P gastrointestinal stromal tumor predicted - sensitive Ripretinib Case Reports/Case Series Actionable In a Phase I trial, treatment with Qinlock (ripretinib) decreased circulating tumor DNA, resulted in stable disease lasting over 26 months in a patient with gastrointestinal stromal tumor harboring a primary KIT V559_G565del mutation and two acquired resistance mutations, KIT V654A and KIT A829P (PMID: 31085175; NCT02571036). 31085175
KIT V560_Y578del KIT V654A gastrointestinal stromal tumor sensitive Sunitinib Preclinical - Cell line xenograft Actionable In a preclinical study, Sutent (sunitinib) inhibited growth of a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del and KIT V654A in culture, and inhibited tumor growth in cell line xenograft models (PMID: 32350132). 32350132
KIT V560_Y578del KIT V654A gastrointestinal stromal tumor predicted - resistant Ripretinib Preclinical - Cell line xenograft Actionable In a preclinical study, Qinlock (ripretinib) resulted in slight decreases in cell viability and KIT signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del and KIT V654A in culture, but failed to suppress tumor growth in cell line xenograft models (PMID: 32350132). 32350132
KIT V560_Y578del KIT V654A gastrointestinal stromal tumor sensitive AZD3229 Preclinical - Cell line xenograft Actionable In a preclinical study, AZD3229 suppressed Kit signaling and cell growth in culture, and inhibited tumor growth in a cell line xenograft model of gastrointestinal stromal tumor harboring KIT V560_Y578del and KIT V654A (PMID: 32350132). 32350132
KIT V560_Y578del KIT V654A gastrointestinal stromal tumor resistant Imatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Gleevec (imatinib) failed to decrease cell viability and KIT signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del and KIT V654A in culture, and did suppress tumor growth in cell line xenograft models (PMID: 32350132). 32350132
KIT V560_Y578del KIT V654A gastrointestinal stromal tumor resistant Regorafenib Preclinical - Cell culture Actionable In a preclinical study, a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del and KIT V654A demonstrated resistance to Stivarga (regorafenib) in culture (PMID: 32350132). 32350132
KIT V560_Y578del KIT V654A gastrointestinal stromal tumor resistant Avapritinib Preclinical - Cell line xenograft Actionable In a preclinical study, Ayvakit (avapritinib) failed to decrease cell viability and KIT signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del and KIT V654A in culture, and did suppress tumor growth in cell line xenograft models (PMID: 32350132). 32350132
KIT A502_Y503dup KIT V654A Advanced Solid Tumor resistant Avapritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT V654A demonstrated resistance to Ayvakit (avapritinib) in culture (PMID: 32350132). 32350132
KIT A502_Y503dup KIT V654A Advanced Solid Tumor resistant Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT V654A demonstrated resistance to Gleevec (imatinib) in culture (PMID: 32350132). 32350132
KIT A502_Y503dup KIT V654A Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT V654A demonstrated sensitivity to Sutent (sunitinib) in culture, resulting in reduced cell viability (PMID: 32350132). 32350132
KIT A502_Y503dup KIT V654A Advanced Solid Tumor resistant Regorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT V654A demonstrated resistance to Stivarga (regorafenib) in culture (PMID: 32350132). 32350132
KIT A502_Y503dup KIT V654A Advanced Solid Tumor sensitive AZD3229 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT V654A demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). 32350132
KIT A502_Y503dup KIT V654A Advanced Solid Tumor decreased response Ripretinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT V654A demonstrated a decreased response to treatment with Qinlock (ripretinib) compared to cells expressing KIT A502_Y503dup alone in culture (PMID: 32350132). 32350132
KIT exon 11 del KIT V654A Advanced Solid Tumor predicted - sensitive THE-630 Preclinical - Cell culture Actionable In a preclinical study, THE-630 treatment inhibited growth of cells co-expressing a KIT exon 11 deletion and KIT V654A in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1292). detail...
KIT exon 9 ins KIT V654A Advanced Solid Tumor predicted - sensitive THE-630 Preclinical - Cell culture Actionable In a preclinical study, THE-630 treatment inhibited growth of cells co-expressing a KIT exon 9 insertion and KIT V654A in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1292). detail...
KIT E554_K558del KIT V654A gastrointestinal stromal tumor predicted - resistant Binimetinib + Imatinib Case Reports/Case Series Actionable In a Phase II trial, KIT V654A was identified as a secondary resistance mutation in a patient with a gastrointestinal stromal tumor harboring a primary KIT E562_L576del mutation who developed resistance to Gleevec (imatinib) and Mektovi (binimetinib) treatment (PMID: 35041493; NCT01991379). 35041493
KIT Q556_V559delinsHT KIT V654A gastrointestinal stromal tumor predicted - resistant Binimetinib + Imatinib Case Reports/Case Series Actionable In a Phase II trial, KIT V654A was identified as a secondary resistance mutation in a patient with a gastrointestinal stromal tumor harboring a primary KIT Q556_V559delinsHT mutation who developed resistance to Gleevec (imatinib) and Mektovi (binimetinib) (PMID: 35041493; NCT01991379). 35041493
KIT Q556_I571del KIT V654A gastrointestinal stromal tumor predicted - resistant Binimetinib + Imatinib Case Reports/Case Series Actionable In a Phase II trial, KIT V654A was identified as a secondary mutation in a patient with a gastrointestinal stromal tumor harboring a primary KIT Q556_I571del mutation who developed resistance to Gleevec (imatinib) and Mektovi (binimetinib) (PMID: 35041493; NCT01991379). 35041493
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 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 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 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 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 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 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 7.4 months (Annals of Oncology 32 (2021): S896-S897; NCT02571036). detail...
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 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 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