Molecular Profile Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Profile Name EZH2 Y641H
Gene Variant Detail

EZH2 Y641H (gain of function)

Relevant Treatment Approaches EZH2 inhibitor

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
EZH2 positive non-Hodgkin lymphoma predicted - sensitive EZH2 inhibitor Tazemetostat Phase I Actionable In a Phase I trial, Tazemetostat (EPZ-6438) treatment resulted in a total response rate of 60% (9/15) in non-Hodgkin lymphoma patients harboring wild-type EZH2 (n=13/14 tested) or an EZH2 Y646H mutation (n=1/14 tested) (ASH 57th Annual Meeting and Exposition, Dec 2015, Abstract #473; NCT01897571). detail...
EZH2 positive diffuse large B-cell lymphoma predicted - sensitive EZH2 inhibitor Tazemetostat Phase I Actionable In a Phase I trial, Tazemetostat (EPZ-6438) treatment in non-Hodgkin lymphoma (NHL) patients carrying wild-type EZH2 or an EZH2 Y646H mutation resulted in an objective response rate of 56% (5/9) among patients with diffuse large B-cell lymphoma (ASH 57th Annual Meeting and Exposition, Dec 2015, Abstract #473; NCT01897571). detail...
EZH2 positive follicular lymphoma predicted - sensitive EZH2 inhibitor Tazemetostat Phase I Actionable In a Phase I trial, Tazemetostat (EPZ-6438) treatment in non-Hodgkin lymphoma (NHL) patients carrying wild-type EZH2 or an EZH2 Y646H mutation resulted in an objective response rate of 60% (3/5) among patients with follicular lymphoma (ASH 57th Annual Meeting and Exposition, Dec 2015, Abstract #473; NCT01897571). detail...
EZH2 A677G follicular lymphoma sensitive EZH2 inhibitor Tazemetostat FDA approved - On Companion Diagnostic Actionable In a Phase II trial that supported FDA approval, Tazverik (tazemetostat) treatment was well-tolerated, resulted in a median progression-free survival of 11.1 months, objective response in 77% (33/43), and stable disease in 23% (10/43) of patients with relapsed/refractory follicular lymphoma, who had two or more prior therapies and harbored EZH2 mutations as detected by an approved test, including EZH2 A682G (corresponds to A677G in the canonical isoform) (Blood (2019) 134 (Supplement_1):123; NCT01897571). detail... detail... detail...
EZH2 Y111D EZH2 A677G B-cell lymphoma resistant EZH2 inhibitor Tazemetostat Preclinical - Cell culture Actionable In a preclinical study, EZH2 Y111D conferred resistance to Tazemetostat (EPZ-6438) when occurring in the same allele as EZH2 A677G in B-cell lymphoma cells in culture (PMID: 26360609). 26360609
EZH2 Y111D EZH2 A677G B-cell lymphoma resistant EZH2 inhibitor 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
EZH2 Y111D EZH2 A677G Advanced Solid Tumor resistant EZH2 inhibitor Tazemetostat Preclinical - Cell culture Actionable In a preclinical study, transformed cells overexpressing EZH2 and carrying simultaneous A677G and Y111D mutations were resistant to Tazemetostat (EPZ-6438) in culture (PMID: 26360609). 26360609
EZH2 Y111D EZH2 A677G Advanced Solid Tumor resistant EZH2 inhibitor 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
EZH2 Y111D Advanced Solid Tumor resistant EZH2 inhibitor Tazemetostat Preclinical - Cell culture Actionable In a preclinical study, over expression of EZH2 Y111D in transformed cells harboring wild-type Ezh2 resulted in resistance to Tazemetostat (EPZ-6438) treatment in culture (PMID: 26360609). 26360609
EZH2 Y111D Advanced Solid Tumor resistant EZH2 inhibitor 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
EZH2 Y111D EZH2 Y641F Advanced Solid Tumor predicted - resistant EZH2 inhibitor 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 EZH2 Y641F Advanced Solid Tumor decreased response EZH2 inhibitor Tazemetostat Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing EZH2 carrying simultaneous Y641F and Y111D mutations demonstrated reduced sensitivity to Tazemetostat (EPZ-6438) in culture (PMID: 26360609). 26360609
EZH2 Y111D SMARCB1 inact mut rhabdoid cancer resistant EZH2 inhibitor Tazemetostat Preclinical - Cell culture Actionable In a preclinical study, over expression of EZH2 Y111D in rhabdoid tumor cells harboring an SMARCB1 inactivating mutation resulted in resistance to Tazemetostat (EPZ-6438) treatment in culture (PMID: 26360609). 26360609
EZH2 Y111N EZH2 F120L diffuse large B-cell lymphoma resistant EZH2 inhibitor EI1 Preclinical - Cell culture Actionable In a preclinical study, diffuse large B-cell lymphoma cells co-expressing EZH2 F120L and EZH2 Y111N were resistant to EI1 in culture, demonstrating no inhibition of cell proliferation (PMID: 28135235). 28135235
EZH2 Y111N EZH2 F120L diffuse large B-cell lymphoma sensitive EED226 Preclinical - Cell culture Actionable In a preclinical study, diffuse large B-cell lymphoma cells co-expressing EZH2 F120L and EZH2 Y111N were sensitive to EED226, demonstrating inhibition of cell proliferation in culture (PMID: 28135235). 28135235
EZH2 Y111N EZH2 F120L Advanced Solid Tumor resistant EZH2 inhibitor Tazemetostat Preclinical - Cell culture Actionable In a preclinical study, a cancer cell line co-expressing EZH2 F120L and EZH2 Y111N was resistant to Tazemetostat (EPZ-6438) in culture, demonstrating no inhibition of cell proliferation (PMID: 28135235). 28135235
EZH2 Y646F follicular lymphoma sensitive EZH2 inhibitor Tazemetostat FDA approved - On Companion Diagnostic Actionable In a Phase II trial that supported FDA approval, Tazverik (tazemetostat) treatment was well-tolerated, resulted in a median progression-free survival of 11.1 months, objective response in 77% (33/43), and stable disease in 23% (10/43) of patients with relapsed or refractory follicular lymphoma, who had two or more prior therapies and harbored EZH2 mutations as detected by an approved test, including EZH2 Y646F (Blood (2019) 134 (Supplement_1):123; NCT01897571). detail... detail... detail...
EZH2 Y646F lymphoma sensitive EZH2 inhibitor Tazemetostat Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with Tazverik (tazemetostat) inhibited proliferation and promoted cell death in lymphoma cell lines harboring EZH2 Y646F in culture, and decreased tumor H3K27Me3 levels in cell line xenograft models (PMID: 24563539). 24563539
EZH2 Y646F diffuse large B-cell lymphoma sensitive EED226 Preclinical - Cell culture Actionable In a preclinical study, a diffuse large B-cell lymphoma cell line harboring EZH2 Y646F demonstrated sensitivity to EED226, resulting in inhibition of cell proliferation in culture (PMID: 28135235). 28135235
EZH2 wild-type melanoma predicted - sensitive EZH2 inhibitor 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 Y646C follicular lymphoma sensitive EZH2 inhibitor Tazemetostat FDA approved - On Companion Diagnostic Actionable In a Phase II trial that supported FDA approval, Tazverik (tazemetostat) treatment was well-tolerated, resulted in a median progression-free survival of 11.1 months, objective response in 77% (33/43), and stable disease in 23% (10/43) of patients with relapsed or refractory follicular lymphoma, who had two or more prior therapies and harbored EZH2 mutations as detected by an approved test, including EZH2 Y646C (Blood (2019) 134 (Supplement_1):123; NCT01897571). detail... detail... detail...
EZH2 Y646S follicular lymphoma sensitive EZH2 inhibitor Tazemetostat FDA approved - On Companion Diagnostic Actionable In a Phase II trial that supported FDA approval, Tazverik (tazemetostat) treatment was well-tolerated, resulted in a median progression-free survival of 11.1 months, objective response in 77% (33/43), and stable disease in 23% (10/43) of patients with relapsed or refractory follicular lymphoma, who had two or more prior therapies and harbored EZH2 mutations as detected by an approved test, including EZH2 Y646S (Blood (2019) 134 (Supplement_1): 123; NCT01897571). detail... detail... detail...
EZH2 Y646S diffuse large B-cell lymphoma sensitive EED226 Preclinical - Cell culture Actionable In a preclinical study, a diffuse large B-cell lymphoma cell line harboring EZH2 Y646S demonstrated sensitivity to EED226, resulting in inhibition of cell proliferation in culture (PMID: 28135235). 28135235
EZH2 A687V follicular lymphoma sensitive EZH2 inhibitor Tazemetostat FDA approved - On Companion Diagnostic Actionable In a Phase II trial that supported FDA approval, Tazverik (tazemetostat) treatment was well-tolerated, resulted in a median progression-free survival of 11.1 months, objective response in 77% (33/43), and stable disease in 23% (10/43) of patients with relapsed/refractory follicular lymphoma, who had two or more prior therapies and harbored EZH2 mutations as detected by an approved test, including EZH2 A692V (corresponds to A687V in the canonical isoform) (Blood (2019) 134 (Supplement_1):123; NCT01897571). detail... detail... detail...
EZH2 Y641N diffuse large B-cell lymphoma sensitive EZH2 inhibitor EED226 + EI1 Preclinical - Cell culture Actionable In a preclinical study, EED226 and EI1 synergistically inhibited cell proliferation in a diffuse large B-cell lymphoma cell line harboring EZH2 Y641N in culture (PMID: 28135235). 28135235
EZH2 Y641N diffuse large B-cell lymphoma no benefit EZH2 inhibitor 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
EZH2 Y641N diffuse large B-cell lymphoma no benefit EZH2 inhibitor 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 sensitive EZH2 inhibitor ACY-957 + GSK126 Preclinical - Cell culture Actionable In a preclinical study, GSK126 enhanced the sensitivity of ACY-957 treatment in DLBCL cells harboring EZH2 Y641N in culture, resulting in increased cell death and elevated levels of H3K27ac (PMID: 25605023). 25605023
EZH2 Y641N melanoma predicted - sensitive EZH2 inhibitor 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 sensitive EZH2 inhibitor GSK126 + Pomalidomide Preclinical - Cell culture Actionable In a preclinical study, the combination of GSK126 and Pomalyst (pomalidomide) synergistically inhibited growth, induced cell death, and led to increased expression of hematopoietic lineage genes and plasma cell differentiation in a diffuse large B-cell lymphoma cell line harboring EZH2 Y641N in culture (PMID: 32906688). 32906688
EZH2 Y641N diffuse large B-cell lymphoma sensitive EED226 Preclinical - Cell culture Actionable In a preclinical study, a diffuse large B-cell lymphoma cell line harboring EZH2 Y641N demonstrated sensitivity to EED226 in culture, resulting in reduced cell viability (PMID: 32906688). 32906688
EZH2 Y641N diffuse large B-cell lymphoma sensitive EED226 Preclinical - Cell line xenograft Actionable In a preclinical study, a diffuse large B-cell lymphoma cell line harboring EZH2 Y641N demonstrated sensitivity to EED226, resulting in inhibition of cell proliferation in culture and delayed tumor growth and tumor regression in a cell line xenograft model (PMID: 28135235). 28135235
EZH2 Y641N diffuse large B-cell lymphoma sensitive ACY-957 + Doxorubicin Preclinical Actionable In a preclinical study, DLBCL cells harboring EZH2 Y641N treated with the combination of ACY-957 and Adriamycin (doxorubicin) resulted in a greater sensitivity to cell death compared to treatment with either agent alone (PMID: 25605023). 25605023
EZH2 Y641N diffuse large B-cell lymphoma sensitive EED226 + Pomalidomide Preclinical - Cell culture Actionable In a preclinical study, the combination of EED226 and Pomalyst (pomalidomide) synergistically inhibited growth of a diffuse large B-cell lymphoma cell line harboring EZH2 Y641N in culture (PMID: 32906688). 32906688
EZH2 Y641N diffuse large B-cell lymphoma sensitive ACY-957 Preclinical Actionable In a preclinical study, DLBCL cells harboring EZH2 Y641N demonstrated sensitivity to ACY-957 in culture, resulting in increased levels of H3K27ac and cell cycle arrest (PMID: 25605023). 25605023
EZH2 Y641N follicular lymphoma sensitive EZH2 inhibitor Tazemetostat FDA approved - On Companion Diagnostic Actionable In a Phase II trial that supported FDA approval, Tazverik (tazemetostat) treatment was well-tolerated, resulted in a median progression-free survival of 11.1 months, objective response in 77% (33/43), and stable disease in 23% (10/43) of patients with relapsed/refractory follicular lymphoma, who had two or more prior therapies and harbored EZH2 mutations as detected by an approved test, including EZH2 Y646N (corresponds to Y641N in the canonical isoform) (Blood (2019) 134 (Supplement_1):123; NCT01897571). detail... detail... detail...
EZH2 Y641N diffuse large B-cell lymphoma sensitive Vorinostat Preclinical Actionable In a preclinical study, DLBCL cells harboring EZH2 Y641N demonstrated sensitivity to Zolinza (vorinostat) in culture, resulting in increased levels of H3K27ac and cell cycle arrest (PMID: 25605023). 25605023
EZH2 Y641N diffuse large B-cell lymphoma sensitive EZH2 inhibitor ACY-957 + DZNeP Preclinical Actionable In a preclinical study, DZNeP enhanced the sensitivity of ACY-957 treatment in DLBCL cells harboring EZH2 Y641N in culture, resulting in increased cell death and elevated levels of H3K27ac (PMID: 25605023). 25605023
EZH2 Y641N diffuse large B-cell lymphoma sensitive EZH2 inhibitor UNC1999 Preclinical Actionable In a preclinical study, UNC1999 treatment reduced H3K27me3 levels, decreased proliferation, and increased cell death in diffuse large B-cell lymphoma cells harboring an EZH2 Y641N mutation in cell culture (PMID: 23614352). 23614352
EZH2 Y641N diffuse large B-cell lymphoma predicted - sensitive EZH2 inhibitor DZNeP Preclinical - Cell culture Actionable In a preclinical study, DZNeP treatment resulted in an increase in the number of dead or sub-G1 cells and increased DNA damage in a diffuse large B-cell lymphoma cell line harboring EZH2 Y641N in culture (PMID: 25605023). 25605023
EZH2 A692V follicular lymphoma sensitive EZH2 inhibitor Tazemetostat FDA approved - On Companion Diagnostic Actionable In a Phase II trial that supported FDA approval, Tazverik (tazemetostat) treatment was well-tolerated, resulted in a median progression-free survival of 11.1 months, objective response in 77% (33/43), and stable disease in 23% (10/43) of patients with relapsed or refractory follicular lymphoma, who had two or more prior therapies and harbored EZH2 mutations as detected by an approved test, including EZH2 A692V (Blood (2019) 134 (Supplement_1):123; NCT01897571). detail... detail... detail...
EZH2 Y641C follicular lymphoma sensitive EZH2 inhibitor Tazemetostat FDA approved - On Companion Diagnostic Actionable In a Phase II trial that supported FDA approval, Tazverik (tazemetostat) treatment was well-tolerated, resulted in a median progression-free survival of 11.1 months, objective response in 77% (33/43), and stable disease in 23% (10/43) of patients with relapsed/refractory follicular lymphoma, who had two or more prior therapies and harbored EZH2 mutations as detected by an approved test, including EZH2 Y646C (corresponds to Y641C in the canonical isoform) (Blood (2019) 134 (Supplement_1):123; NCT01897571). detail... detail... detail...
EZH2 A682G follicular lymphoma sensitive EZH2 inhibitor Tazemetostat FDA approved - On Companion Diagnostic Actionable In a Phase II trial that supported FDA approval, Tazverik (tazemetostat) treatment was well-tolerated, resulted in a median progression-free survival of 11.1 months, objective response in 77% (33/43), and stable disease in 23% (10/43) of patients with relapsed or refractory follicular lymphoma, who had two or more prior therapies and harbored EZH2 mutations as detected by an approved test, including EZH2 A682G (Blood (2019) 134 (Supplement_1):123; NCT01897571). detail... detail... detail...
EZH2 A682G lymphoma sensitive EZH2 inhibitor Tazemetostat Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with Tazemetostat (EPZ-6438) inhibited proliferation and induced apoptosis in lymphoma cell lines harboring EZH2 A682G in culture, and complete tumor regression in cell line xenograft models (PMID: 24563539). 24563539
EZH2 over exp lung non-small cell carcinoma sensitive EZH2 inhibitor JQEZ5 Preclinical Actionable In a preclinical study, JQEZ5 inhibited proliferation of human EZH2-overexpressing non-small cell lung cancer cells in culture and induced tumor regression in mouse models of EZH2-overexpressing lung adenocarcinoma (PMID: 27312177). 27312177
EZH2 over exp medulloblastoma predicted - sensitive EZH2 inhibitor MC3629 Preclinical - Cell line xenograft Actionable In a preclinical study, MC3629 decreased proliferation and induced apoptosis in human and mouse primary SHH-subgroup medulloblastoma (SHH-MB) derived stem-cell like cells expressing high EZH2 levels in culture, decreased viability of a human SHH-MB cell line expressing high EZH2 in culture, and increased apoptosis and decreased growth of human SHH-MB cell line derived stem-cell like cells in culture and in xenograft models (PMID: 28978137). 28978137
EZH2 Y641F diffuse large B-cell lymphoma sensitive EZH2 inhibitor 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
EZH2 Y641F diffuse large B-cell lymphoma sensitive EED226 + Pomalidomide Preclinical - Cell culture Actionable In a preclinical study, the combination of EED226 and Pomalyst (pomalidomide) synergistically inhibited growth of a diffuse large B-cell lymphoma cell line harboring EZH2 Y641F in culture (PMID: 32906688). 32906688
EZH2 Y641F lymphoma sensitive EZH2 inhibitor EPZ005687 Preclinical - Cell culture Actionable In a preclinical study, treatment with EPZ005687 decreased proliferation and induced cell killing in a lymphoma cell line harboring EZH2 Y641F in culture (PMID: 23023262). 23023262
EZH2 Y641F follicular lymphoma sensitive EZH2 inhibitor Tazemetostat FDA approved - On Companion Diagnostic Actionable In a Phase II trial that supported FDA approval, Tazverik (tazemetostat) treatment was well-tolerated, resulted in a median progression-free survival of 11.1 months, objective response in 77% (33/43), and stable disease in 23% (10/43) of patients with relapsed/refractory follicular lymphoma, who had two or more prior therapies and harbored EZH2 mutations as detected by an approved test, including EZH2 Y646F (corresponds to Y641F in the canonical isoform) (Blood (2019) 134 (Supplement_1):123; NCT01897571). detail... detail... detail...
EZH2 Y641F diffuse large B-cell lymphoma sensitive EZH2 inhibitor GSK126 + Pomalidomide Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of GSK126 and Pomalyst (pomalidomide) synergistically inhibited growth, induced cell death, and led to increased expression of hematopoietic lineage genes and plasma cell differentiation in a diffuse large B-cell lymphoma cell line harboring EZH2 Y641F in culture, and inhibited tumor growth in cell line xenograft models (PMID: 32906688). 32906688
EZH2 Y641F diffuse large B-cell lymphoma sensitive EED226 Preclinical - Cell culture Actionable In a preclinical study, a diffuse large B-cell lymphoma cell line harboring EZH2 Y641F demonstrated sensitivity to EED226 in culture, resulting in reduced cell viability (PMID: 32906688). 32906688
EZH2 Y641F diffuse large B-cell lymphoma sensitive EZH2 inhibitor GSK126 + Lenalidomide Preclinical - Cell culture Actionable In a preclinical study, the combination of GSK126 and Revlimid (lenalidomide) synergistically inhibited growth of a diffuse large B-cell lymphoma cell line harboring EZH2 Y641F in culture (PMID: 32906688). 32906688
EZH2 Y641S melanoma predicted - sensitive EZH2 inhibitor 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 Y641S follicular lymphoma sensitive EZH2 inhibitor Tazemetostat FDA approved - On Companion Diagnostic Actionable In a Phase II trial that supported FDA approval, Tazverik (tazemetostat) treatment was well-tolerated, resulted in a median progression-free survival of 11.1 months, objective response in 77% (33/43), and stable disease in 23% (10/43) of patients with relapsed/refractory follicular lymphoma, who had two or more prior therapies and harbored EZH2 mutations as detected by an approved test, including EZH2 Y646S (corresponds to Y641S in the canonical isoform) (Blood (2019) 134 (Supplement_1):123; NCT01897571). detail... detail... detail...
EZH2 Y641S diffuse large B-cell lymphoma sensitive ACY-957 Preclinical Actionable In a preclinical study, DLBCL cells harboring EZH2 Y641S demonstrated sensitivity to ACY-957 in culture, resulting in increased levels of H3K27ac and cell cycle arrest (PMID: 25605023). 25605023
EZH2 Y641S diffuse large B-cell lymphoma decreased response EZH2 inhibitor DZNeP Preclinical - Cell culture Actionable In a preclinical study, treatment with DZNeP resulted in a slight increase in number of dead or sub-G1 cells and accumulation of DNA damage in a diffuse large B-cell lymphoma cell line harboring EZH2 Y641S in culture (PMID: 25605023). 25605023
EZH2 Y641S diffuse large B-cell lymphoma sensitive Vorinostat Preclinical Actionable In a preclinical study, DLBCL cells harboring EZH2 Y641S demonstrated sensitivity to Zolinza (vorinostat) in culture, resulting in increased levels of H3K27ac and cell cycle arrest (PMID: 25605023). 25605023
EZH2 Y641S diffuse large B-cell lymphoma decreased response EZH2 inhibitor 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 Y641S diffuse large B-cell lymphoma sensitive EZH2 inhibitor ACY-957 + DZNeP Preclinical Actionable In a preclinical study, DZNeP enhanced the sensitivity of ACY-957 treatment in DLBCL cells harboring EZH2 Y641S in culture, resulting in increased cell death and elevated levels of H3K27ac (PMID: 25605023). 25605023
EZH2 Y641S diffuse large B-cell lymphoma sensitive EZH2 inhibitor ACY-957 + GSK126 Preclinical - Cell culture Actionable In a preclinical study, GSK126 enhanced the sensitivity of ACY-957 treatment in DLBCL cells harboring EZH2 Y641S in culture, resulting in increased cell death and elevated levels of H3K27ac (PMID: 25605023). 25605023
EZH2 Y646H non-Hodgkin lymphoma sensitive EZH2 inhibitor Tazemetostat Phase I Actionable In a Phase I trial, Tazemetostat (EPZ-6438) treatment resulted in partial response for more than 16 weeks in a non-Hodgkin lymphoma patient harboring a EZH2 Y646H mutation (ASH 57th Annual Meeting and Exposition, Dec 2015, Abstract #473; NCT01897571). detail...
EZH2 Y646H diffuse large B-cell lymphoma predicted - sensitive EZH2 inhibitor Tazemetostat Case Reports/Case Series Actionable In a Phase I trial, Tazemetostat (EPZ-6438) treatment resulted in a durable partial response in a patient with diffuse large B-cell lymphoma harboring EZH2 Y646H, and the patient was progression-free for 16 months (PMID: 29650362; NCT01897571). 29650362
EZH2 Y646H follicular lymphoma sensitive EZH2 inhibitor Tazemetostat FDA approved - On Companion Diagnostic Actionable In a Phase II trial that supported FDA approval, Tazverik (tazemetostat) treatment was well-tolerated, resulted in a median progression-free survival of 11.1 months, objective response in 77% (33/43), and stable disease in 23% (10/43) of patients with relapsed or refractory follicular lymphoma, who had two or more prior therapies and harbored EZH2 mutations as detected by an approved test, including EZH2 Y646H (Blood (2019) 134 (Supplement_1):123; NCT01897571). detail... detail... detail...
EZH2 T678_R679delinsKK acute myeloid leukemia resistant EZH2 inhibitor Tazemetostat Preclinical - Cell culture Actionable In a preclinical study, a murine acute myeloid leukemia cell line expressing EZH2 T678_R679delinsKK were resistant to Tazemetostat (EPZ-6438) in culture (PMID: 28231254). 28231254
EZH2 mutant myelodysplastic/myeloproliferative neoplasm not applicable N/A Guideline Prognostic EZH2 mutations are associated with a poor prognosis in patients with myelodysplastic/myeloproliferative neoplasm (NCCN.org). detail...
EZH2 mutant myelofibrosis not applicable N/A Guideline Prognostic EZH2 mutations are associated with inferior overall survival in patients with myelofibrosis (NCCN.org). detail...
EZH2 mutant diffuse large B-cell lymphoma sensitive EZH2 inhibitor MK2206 + Tazemetostat Preclinical - Cell culture Actionable In a preclinical study, Tazemetostat (EPZ-6438) and MK-2206 synergistically inhibited proliferation of diffuse large B-cell lymphoma cell lines harboring EZH2 mutations in culture (PMID: 28835384). 28835384
EZH2 mutant diffuse large B-cell lymphoma sensitive A-395 Preclinical - Cell line xenograft Actionable In a preclinical study, a diffuse large B-cell lymphoma cell line harboring an EZH2 mutation demonstrated sensitivity to A-395, showing inhibition of tumor growth, however, due to its chemical properties A-395 will not proceed to clinical development (PMID: 28135237). 28135237
EZH2 mutant myelodysplastic syndrome not applicable N/A Guideline Prognostic EZH2 mutations are associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org). detail...
EZH2 mutant diffuse large B-cell lymphoma sensitive EZH2 inhibitor Tamatinib + Tazemetostat Preclinical - Cell culture Actionable In a preclinical study, Tazemetostat (EPZ-6438) and Tamatinib (R406) synergistically inhibited proliferation of diffuse large B-cell lymphoma cell lines harboring EZH2 mutations in culture (PMID: 28835384). 28835384
EZH2 mutant diffuse large B-cell lymphoma sensitive EZH2 inhibitor Ibrutinib + Tazemetostat Preclinical - Cell culture Actionable In a preclinical study, Tazemetostat (EPZ-6438) and Imbruvica (ibrutinib) synergistically inhibited proliferation of diffuse large B-cell lymphoma cell lines harboring EZH2 mutations in culture (PMID: 28835384). 28835384
EZH2 mutant follicular lymphoma sensitive EZH2 inhibitor Tazemetostat Guideline Actionable Tazverik (tazemetostat) is included in guidelines as a second-line or subsequent therapy for patients with follicular lymphoma harboring EZH2 mutations (NCCN.org). detail...
EZH2 mutant follicular lymphoma sensitive EZH2 inhibitor Tazemetostat Phase II Actionable In a Phase II trial, Tazverik (tazemetostat) treatment resulted in an objective response in 71% (20/28, 3 complete response, 17 partial response) and stable disease in 29% (8/28) of patients with relapsed or refractory follicular lymphoma harboring EZH2 mutations, while only resulted in object response rate in 33% (18/54, 3 complete response, 15 partial response) and stable disease in 31% (16/54) of patients with EZH2 wild-type disease (PMID: 29980507). 29980507
EZH2 mutant diffuse large B-cell lymphoma sensitive EZH2 inhibitor Everolimus + Tazemetostat Preclinical - Cell culture Actionable In a preclinical study, Tazemetostat (EPZ-6438) and Afinitor (everolimus) synergistically inhibited proliferation of diffuse large B-cell lymphoma cell lines harboring EZH2 mutations in culture (PMID: 28835384). 28835384
EZH2 mutant diffuse large B-cell lymphoma sensitive EZH2 inhibitor Tazemetostat + Trametinib Preclinical - Cell culture Actionable In a preclinical study, Tazemetostat (EPZ-6438) and Mekinist (trametinib) synergistically inhibited proliferation of diffuse large B-cell lymphoma cell lines harboring EZH2 mutations in culture (PMID: 28835384). 28835384
EZH2 mutant diffuse large B-cell lymphoma sensitive EZH2 inhibitor Tazemetostat Preclinical - Cell line xenograft Actionable In a preclinical study, diffuse large B-cell lymphoma cell lines harboring EZH2 mutations demonstrated increased sensitivity to Tazemetostat (EPZ-6438) treatment-induced growth inhibition, apoptosis, and tumor inhibition compared to EZH2 wild-type cell lines (PMID: 28835384). 28835384
EZH2 mutant essential thrombocythemia not applicable N/A Guideline Prognostic The presence of at least one mutation in either SH2B3, IDH2, U2AF1, SRSF2, SF3B1, EZH2, TP53, or RUNX1 is associated with inferior overall survival in patients with essential thrombocythemia, EZH2 mutations are also associated with inferior leukemia-free survival (NCCN.org). detail...
EZH2 mutant diffuse large B-cell lymphoma sensitive EZH2 inhibitor Idelalisib + Tazemetostat Preclinical - Cell culture Actionable In a preclinical study, Tazemetostat (EPZ-6438) and Zydelig (idelalisib) synergistically inhibited proliferation of diffuse large B-cell lymphoma cell lines harboring EZH2 mutations in culture (PMID: 28835384). 28835384
EZH2 Y646N diffuse large B-cell lymphoma sensitive EED226 Preclinical - Cell culture Actionable In a preclinical study, a diffuse large B-cell lymphoma cell line harboring EZH2 Y646N demonstrated sensitivity to EED226, resulting in inhibition of cell proliferation in culture (PMID: 28135235). 28135235
EZH2 Y646N lymphoma sensitive EZH2 inhibitor Tazemetostat Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with Tazemetostat (EPZ-6438) inhibited proliferation and induced apoptosis in lymphoma cell lines harboring EZH2 Y646N in culture, and complete eradication of tumors in cell line xenograft models (PMID: 24563539). 24563539
EZH2 Y646N melanoma sensitive EZH2 inhibitor 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 Y646N follicular lymphoma sensitive EZH2 inhibitor Tazemetostat FDA approved - On Companion Diagnostic Actionable In a Phase II trial that supported FDA approval, Tazverik (tazemetostat) treatment was well-tolerated, resulted in a median progression-free survival of 11.1 months, objective response in 77% (33/43), and stable disease in 23% (10/43) of patients with relapsed or refractory follicular lymphoma, who had two or more prior therapies and harbored EZH2 mutations as detected by an approved test, including EZH2 Y646N (Blood (2019) 134 (Supplement_1):123; NCT01897571). detail... detail... detail...
EZH2 Y641H follicular lymphoma sensitive EZH2 inhibitor Tazemetostat FDA approved - On Companion Diagnostic Actionable In a Phase II trial that supported FDA approval, Tazverik (tazemetostat) treatment was well-tolerated, resulted in a median progression-free survival of 11.1 months, objective response in 77% (33/43), and stable disease in 23% (10/43) of patients with relapsed/refractory follicular lymphoma, who had two or more prior therapies and harbored EZH2 mutations as detected by an approved test, including EZH2 Y646H (corresponds to Y641H in the canonical isoform) (Blood (2019) 134 (Supplement_1):123; NCT01897571). detail... detail... detail...
EZH2 Y641H melanoma predicted - sensitive EZH2 inhibitor 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
Clinical Trial Phase Therapies Title Recruitment Status