# Tazemetostat

Source: https://onco.cc/drugs/tazemetostat/  
OnCo record `tazemetostat` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Tazemetostat was the first EZH2 inhibitor, approved for epithelioid sarcoma and follicular lymphoma in 2020 and withdrawn worldwide in 2026 after secondary blood cancers.

## Summary

Accelerated approvals in 2020 (epithelioid sarcoma; relapsed EZH2-mutant or option-less FL). Modest response rates (15% and ~35-69%) with good tolerability; SYMPHONY-1 combined it with lenalidomide-rituximab. Withdrawn worldwide in March 2026 over secondary haematologic malignancies (T-ALL, MDS), ending the EZH2 class in lymphoma for now.

## Fields

- Kind: Treatment
- Status: withdrawn
- Last checked: 2026-09-08
- Tags: gap-fill
- Brand: Tazverik
- Modality: Small-molecule EZH2 inhibitor
- Mechanism: SAM-competitive inhibitor of EZH2 methyltransferase (wild-type and mutant), reducing H3K27me3 and de-repressing differentiation genes.
- Approvals: US 2020: Epithelioid sarcoma; relapsed FL (EZH2-mutant after 2 lines; wild-type without alternatives)

## Notes

- Lymphoma biology: the EZH2 mutations this drug was built for are gain-of-function changes at a single tyrosine in the SET domain, Tyr641 in the original numbering and Tyr646 now, which make the enzyme better at writing the trimethyl mark and worse at making the first methylation, so H3K27me3 accumulates and the germinal-centre exit stays shut. They occur in 7.2% of follicular lymphomas and 21.7% of germinal-centre diffuse large B-cell lymphomas and are absent from the activated B-cell-like subtype (Morin 2010). This is one of only two genotype-selected drug choices in B-cell lymphoma.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Tazemetostat
- Wikipedia: https://en.wikipedia.org/wiki/Tazemetostat
- Morin et al., Nat Genet 2010: somatic EZH2 Tyr641 mutations in follicular and germinal-centre diffuse large B-cell lymphoma: https://doi.org/10.1038/ng.518

## Connected records

- cancers: [Atypical teratoid/rhabdoid tumour (ATRT)](https://onco.cc/cancers/atrt/), [Chordoma](https://onco.cc/cancers/chordoma/), [Epithelioid sarcoma](https://onco.cc/cancers/epithelioid-sarcoma/), [Follicular lymphoma](https://onco.cc/cancers/follicular-lymphoma/), [Poorly differentiated chordoma (SMARCB1-deficient)](https://onco.cc/cancers/poorly-differentiated-chordoma/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/)
- technologies: [Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET)](https://onco.cc/technologies/epigenetic-drugs/)
- targets: [EZH2](https://onco.cc/targets/ezh2/)
- companies: [Ipsen](https://onco.cc/companies/ipsen/)
- trials: [A Clinical Study of SHR-4394 in Combination With Anti-tumor Therapy in Prostate Cancer](https://onco.cc/trials/nct07407283/), [A Study to Assess the Efficacy, Safety, Pharmacodynamics, and Pharmacokinetics of Tazemetostat in Combination With Lenalidomide Plus Rituximab Versus ](https://onco.cc/trials/nct04224493/), [A Study to Evaluate Safety, Drug Levels and Effectiveness of CC-92480 (BMS-986348) in Combination With Other Treatments in Participants With Relapsed ](https://onco.cc/trials/nct05372354/), [NCI-COG Pediatric MATCH (APEC1621)](https://onco.cc/trials/pediatric-match/), [Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)](https://onco.cc/trials/nct03213665/), [Tazemetostat with doxorubicin as front-line therapy for advanced epithelioid sarcoma (EZH-301 run-in)](https://onco.cc/trials/tazemetostat-doxorubicin-es/)
- biomarkers: [EZH2 gain-of-function mutation (Tyr646, originally Tyr641)](https://onco.cc/biomarkers/ezh2-y646-mutation/)
- terms: [BAP1 loss](https://onco.cc/terms/bap1-loss/), [Epigenetic progenitor theory: cancer without a first mutation](https://onco.cc/terms/epigenetic-progenitor-theory/), [FLIPI, FLIPI2 and POD24 (follicular lymphoma risk)](https://onco.cc/terms/flipi/), [Indication withdrawal](https://onco.cc/terms/approval-withdrawal/)
- pathways: [Cold tumours: immune deserts and exclusion](https://onco.cc/pathways/immune-desert-exclusion/), [Lineage plasticity & neuroendocrine transformation](https://onco.cc/pathways/lineage-plasticity-neuroendocrine/), [MicroRNAs in cancer](https://onco.cc/pathways/micrornas-in-cancer/)
- roadmaps: [Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome](https://onco.cc/roadmaps/epigenetics-roadmap/)

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