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Therapy Name | GSK126 |
Synonyms | |
Therapy Description |
GSK126 selectively inhibits EZH2, resulting in decreased H3K27 tri-methylation, and potentially leading to decreased tumor cell proliferation and reduced tumor growth (PMID: 23051747, PMID: 25686104). |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
---|---|---|---|---|
GSK126 | GSK2816126|GSK-126 | EZH2 inhibitor 18 | GSK126 selectively inhibits EZH2, resulting in decreased H3K27 tri-methylation, and potentially leading to decreased tumor cell proliferation and reduced tumor growth (PMID: 23051747, PMID: 25686104, PMID: 31471312). |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
EZH2 Y641H | melanoma | predicted - sensitive | GSK126 | Preclinical - Cell culture | Actionable | In a preclinical study, GSK126 inhibited H3K27 trimethylation and reversed transcriptional silencing in human melanoma cells harboring EZH2 Y641H in culture (PMID: 26936398). | 26936398 |
ARID1A mutant | ovarian cancer | sensitive | GSK126 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, GSK126 selectively inhibited growth of ARID1A-mutant ovarian cancer cells in culture, and induced tumor regression in ARID1A-mutant ovarian cancer xenograft models (PMID: 25686104). | 25686104 |
EZH2 Y111D EZH2 A677G | B-cell lymphoma | resistant | GSK126 | Preclinical - Cell culture | Actionable | In a preclinical study, EZH2 Y111D conferred resistance to GSK126 when occurred in the same allele as EZH2 A677G in B-cell lymphoma cells in culture (PMID: 26360609). | 26360609 |
ATRX fusion | neuroblastoma | predicted - sensitive | GSK126 | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with GSK126 resulted in reduced proliferation and increased apoptosis of neuroblastoma cell lines harboring in-frame ATRX fusions in culture (PMID: 31631027). | 31631027 |
EZH2 Y111D EZH2 Y641F | Advanced Solid Tumor | predicted - resistant | GSK126 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells overexpressing EZH2 and carrying simultaneous Y641F and Y111D mutations demonstrated reduced sensitivity to GSK126 in culture (PMID: 26360609). | 26360609 |
EZH2 Y111D | Advanced Solid Tumor | resistant | GSK126 | Preclinical - Cell culture | Actionable | In a preclinical study, over expression of EZH2 Y111D in transformed cells harboring wild-type Ezh2 resulted in resistance to GSK126 treatment in culture (PMID: 26360609). | 26360609 |
ARID1A wild-type | ovarian cancer | no benefit | GSK126 | Preclinical - Cell culture | Actionable | In a preclinical study, GSK126 had no significant effect on the growth of ovarian cancer cells with wild-type ARID1A in culture (PMID: 25686104). | 25686104 |
Unknown unknown | Advanced Solid Tumor | not applicable | GSK126 | Phase I | Actionable | In a Phase I trial, GSK126 was tolerated and demonstrated preliminary efficacy, resulted in partial response in 2% (1/41) and stable disease in 34% (14/41) of patients with advanced solid tumor (n=21) or B-cell lymphoma (n=20) (PMID: 31471312; NCT02082977). | 31471312 |
EZH2 Y641S | melanoma | predicted - sensitive | GSK126 | Preclinical - Cell culture | Actionable | In a preclinical study, GSK126 reversed transcriptional silencing in human melanoma cells harboring wild-type EZH2 Y641S in culture (PMID: 26936398). | 26936398 |
EZH2 Y641N | melanoma | predicted - sensitive | GSK126 | Preclinical - Cell culture | Actionable | In a preclinical study, GSK126 inhibited H3K27 trimethylation and reversed transcriptional silencing in human melanoma cells harboring EZH2 Y641N in culture (PMID: 26936398). | 26936398 |
EZH2 Y641N | diffuse large B-cell lymphoma | no benefit | GSK126 | Preclinical - Cell culture | Actionable | In a preclinical study, GSK126 alone did not alter cell-cycle progression in survival in a diffuse large B-cell lymphoma cell line harboring EZH2 Y641N in culture (PMID: 25605023). | 25605023 |
EZH2 Y641N | diffuse large B-cell lymphoma | no benefit | GSK126 | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with GSK126 alone did not result in reduced cell viability in a diffuse large B-cell lymphoma cell line harboring EZH2 Y641N in culture (PMID: 32906688). | 32906688 |
Unknown unknown | B-cell lymphoma | not applicable | GSK126 | Phase I | Actionable | In a Phase I trial, GSK126 was tolerated and demonstrated preliminary efficacy, resulted in partial response in 2% (1/41) and stable disease in 34% (14/41) of patients with advanced solid tumor (n=21) or B-cell lymphoma (n=20) (PMID: 31471312; NCT02082977). | 31471312 |
EZH2 Y641S | diffuse large B-cell lymphoma | decreased response | GSK126 | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with GSK126 did not alter cell-cycle progression or decrease survival in a diffuse large B-cell lymphoma cell line harboring EZH2 Y641S in culture (PMID: 25605023). | 25605023 |
EZH2 Y641F | diffuse large B-cell lymphoma | sensitive | GSK126 | Preclinical - Cell culture | Actionable | In a preclinical study, a diffuse large B-cell lymphoma cell line demonstrated sensitivity to GSK126 in culture, resulting in reduced cell viability (PMID: 32906688). | 32906688 |
ARID1A dec exp | ovarian cancer | sensitive | GSK126 | Preclinical - Cell culture | Actionable | In a preclinical study, GSK126 inhibited growth of ovarian cancer cells with knockdown of ARID1A expression in culture (PMID: 25686104). | 25686104 |
EZH2 wild-type | melanoma | predicted - sensitive | GSK126 | Preclinical - Cell culture | Actionable | In a preclinical study, GSK126 inhibited H3K27 trimethylation in human melanoma cells harboring wild-type EZH2 in culture (PMID: 26936398). | 26936398 |
EZH2 Y646N | melanoma | sensitive | GSK126 | Preclinical - Cell culture | Actionable | In a preclinical study, GSK126 treatment inhibited cell growth via suppression of downstream tumor suppressor gene targets and induced apoptosis in melanoma cells harboring EZH2 Y646N in culture (PMID: 26304929). | 26304929 |
EZH2 Y111D EZH2 A677G | Advanced Solid Tumor | resistant | GSK126 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells overexpressing EZH2 and carrying simultaneous A677G and Y111D mutations were resistant to GSK126 in culture (PMID: 26360609). | 26360609 |
KDM6A loss | multiple myeloma | sensitive | GSK126 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a multiple myeloma cell line demonstrated sensitivity to treatment with GSK126, resulting in decreased viability in culture and decreased tumor growth in xenograft models (PMID: 29045832). | 29045832 |
KDM6A loss | bladder urothelial carcinoma | sensitive | GSK126 | Preclinical - Cell culture | Actionable | In a preclinical study, KDM6A-null urothelial bladder carcinoma cell lines demonstrated sensitivity to GSK126, resulting in decreased proliferation in culture (PMID: 28228601). | 28228601 |
ARID1A mut PIK3CA act mut | ovarian cancer | sensitive | GSK126 | Preclinical - Cell culture | Actionable | In a preclinical study, expression of a constitutively active PIK3CA mutation in ARID1A-mutant ovarian cancer cell lines enhanced growth inhibition by GSK126 in culture (PMID: 25686104). | 25686104 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT02082977 | Phase I | GSK126 | A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK2816126 in Subjects With Relapsed/Refractory Diffuse Large B Cell and Transformed Follicular Lymphoma | Terminated | USA | 2 |