Molecular Profile Detail

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Profile Name EZH2 Y641F
Gene Variant Detail

EZH2 Y641F (gain of function)

Relevant Treatment Approaches EZH2 inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 + 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 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 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 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 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 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
Clinical Trial Phase Therapies Title Recruitment Status