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DRUG CLASS:

EZH1 inhibitor

20d
A Phase 1/2, Open-label Study of Valemetostat in Combination With Rituximab and Lenalidomide in Relapsed or Refractory Follicular Lymphoma (clinicaltrials.gov)
P1/2, N=16, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=60 --> 16
Enrollment closed • Enrollment change
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Rituxan (rituximab) • lenalidomide • Ezharmia (valemetostat)
1m
EZH1/2 inhibition improves immunotherapy response through MHC Class II de-repression and neutrophil reprogramming. (PubMed, bioRxiv)
MHC Class II blockade lowered the ability of bone marrow to boost tumor growth, and reduced the ability of valemetostat with anti-PD1 to reduce tumoroid growth. Patient samples revealed a strong negative correlation between EZH2 and MHC Class II, suggesting that targeting EZH2 activity could lead to marked increase in MHC Class II and improve treatment responses in lung squamous cell carcinomas.
Journal
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CD8 (cluster of differentiation 8) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1)
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Ezharmia (valemetostat)
2ms
The role of EZH2 dysregulation in the pathogenesis of B-cell lymphomas and its implications as a target therapy. (PubMed, Front Oncol)
Valemetostat, which inhibits EZH1/2, as well as tazemetostat in combination with other drugs have been subject of recent research. The purpose of this article is to review the role of EZH2 in normal B cell differentiation and in the pathogenesis of B-Cell lymphomas.
Review • Journal • IO biomarker
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EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit)
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EZH2 mutation
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Tazverik (tazemetostat) • Ezharmia (valemetostat)
3ms
Enrollment change • Trial initiation date
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KLK3 (Kallikrein-related peptidase 3)
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Nubeqa (darolutamide) • Ezharmia (valemetostat)
3ms
DS3201-A-J101: DS-3201b in Participants With Lymphomas (clinicaltrials.gov)
P1, N=100, Active, not recruiting, Daiichi Sankyo Co., Ltd. | Trial completion date: Dec 2026 --> Dec 2027
Trial completion date
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Ezharmia (valemetostat)
3ms
HHV-6A Drives Epigenetic Reprogramming via an EZH2-SIRT1 Axis to Sustain Mutant p53 and Reshape Oncogenic Inflammatory Signaling. (PubMed, Viruses)
Pharmacological inhibition of EZH2 using DS-3201 reproduced some of the molecular effects of viral infection, including increased mutp53 stability...Indeed, the inhibition of SIRT1 with EX-527 reversed mutp53 accumulation but restored c-Myc expression and increased extracellular IL-6 release...These results establish a mechanistic link between viral infection, epigenetic remodeling, and oncogenic dependency. They also suggest that targeting IL-6 signaling could represent a therapeutic vulnerability in HHV-6A-associated thyroid cancer, particularly in combination with SIRT1 inhibitors.
Journal
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TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • IL6 (Interleukin 6)
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TP53 mutation • EZH2 mutation
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selisistat (SEN-196) • Ezharmia (valemetostat)
3ms
Trial initiation date
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ARID1A (AT-rich interaction domain 1A) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
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Ezharmia (valemetostat)
3ms
Assessing Treatment of T-Cell Lymphoma With GW5282 in Combination With Golidocitinib (BEI-DOU3) (clinicaltrials.gov)
P1/2, N=165, Recruiting, Dizal Pharmaceuticals | Not yet recruiting --> Recruiting
Enrollment open
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doxorubicin hydrochloride • cyclophosphamide • golidocitinib (DZD4205)
4ms
New P1/2 trial
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doxorubicin hydrochloride • cyclophosphamide • golidocitinib (DZD4205)
4ms
Enhancer of Zeste Homolog 1 and 2 Inhibitor-Induced Colitis Mimicking Immune Checkpoint Inhibitor-Induced Colitis. (PubMed, Intern Med)
An 80-year-old woman with relapsed nodal T-follicular helper cell lymphoma, not otherwise specified, developed severe watery diarrhea during valemetostat therapy...To the best of our knowledge, this is the first reported case of enhancer of zeste homolog 1 and 2 (EZH1/2) inhibitor-induced colitis. EZH1/2 inhibition may lead to T cell-mediated intestinal injury through epigenetic dysregulation; therefore, patients receiving EZH1/2 inhibitors who develop persistent diarrhea should undergo early endoscopic and histological evaluations.
Journal • Checkpoint inhibition
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CD8 (cluster of differentiation 8) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit)
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Ezharmia (valemetostat)
4ms
New P1 trial
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Nubeqa (darolutamide) • Ezharmia (valemetostat)