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HOW TAZVERIK® (tazemetostat) WORKS

TAZVERIK: mechanism of action as an EZH2 inhibitor1

EZH2 is a methyltransferase that plays a role in epithelioid sarcoma pathogenesis1-3

  • INI1 loss is present in >90% of patients with epithelioid sarcoma.4,5
  • Preclinical in vitro and in vivo models show that loss or dysfunction of INI1 can lead to aberrant EZH2 activity or expression and a resulting oncogenic dependence on EZH2.1
Aberrant EZH2
activity1,2,6,7
TODO
EZH2 inhibition by TAZVERIK1,2,6,7
TODO

INI1=integrase interactor 1.

References: 1. TAZVERIK (tazemetostat) Prescribing Information. Cambridge, MA: Epizyme, Inc., July 2020. 2. Italiano A. Role of the EZH2 histone methyltransferase as a therapeutic target in cancer. Pharmacol Ther. 2016;165:26-31. 3. Siontis BL, Chugh R, and Schuetze SM. The potential of emerging therapeutics for epithelioid sarcoma. Expert Opin Orphan Drugs. 2017;5(12):983-989. 4. Hollman TJ and Hornick JL. INI1-deficient tumors: Diagnostic features and molecular genetics. Am J Surg Pathol. 2011;35(10):e47-63. 5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Soft Tissue Sarcoma V.2.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed July 8, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 6. Gan L, Yang Y, Li Q, et al. Epigenetic regulation of cancer progression by EZH2: from biological insights to therapeutic potential. Biomark Res. 2018;6:10. 7. Wilson BG, Wang X, Shen X, et al. Epigenetic antagonism between polycomb and SWI/SNF complexes during oncogenic transformation. Cancer Cell. 2010;18(4):316-328.

Learn more about locally advanced and metastatic epithelioid sarcoma.

epithelioid sarcoma

See how TAZVERIK performed
in the clinical study.

efficacy
INDICATION AND IMPORTANT SAFETY INFORMATION

INDICATION

TAZVERIK is indicated for the treatment of adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

IMPORTANT SAFETY INFORMATION

Warnings and Precautions

  • Secondary Malignancies

The risk of developing secondary malignancies is increased following treatment with TAZVERIK. Across clinical trials of 729 adults who received TAZVERIK 800 mg twice daily, myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) occurred in 0.7% of patients. One pediatric patient developed T‑cell lymphoblastic lymphoma (T‑LBL). Monitor patients long-term for the development of secondary malignancies.

  • Embryo-Fetal Toxicity

Based on findings from animal studies and its mechanism of action, TAZVERIK can cause fetal harm when administered to pregnant women. There are no available data on TAZVERIK use in pregnant women to inform the drug‑associated risk. Administration of tazemetostat to pregnant rats and rabbits during organogenesis resulted in dose‑dependent increases in skeletal developmental abnormalities in both species beginning at maternal exposures approximately 1.5 times the adult human exposure (area under the plasma concentration time curve [AUC0‑45h]) at the 800 mg twice daily dose.

Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TAZVERIK and for 6 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with TAZVERIK and for 3 months after the final dose.

Adverse Reactions

In 62 clinical study patients with epithelioid sarcoma receiving TAZVERIK 800 mg twice daily: Serious adverse reactions occurred in 37% of patients who received TAZVERIK. Serious adverse reactions occurring in ≥3% were hemorrhage, pleural effusion, skin infection, dyspnea, pain, and respiratory distress. The most common (≥20%) adverse reactions were pain (52%), fatigue (47%), nausea (36%), decreased appetite (26%), vomiting (24%), and constipation (21%).

Drug Interactions

Avoid coadministration of strong or moderate CYP3A inhibitors with TAZVERIK. If coadministration of moderate CYP3A inhibitors cannot be avoided, reduce TAZVERIK dose.

Avoid coadministration of moderate and strong CYP3A inducers with TAZVERIK, which may decrease the efficacy of TAZVERIK.

Coadministration of TAZVERIK with CYP3A substrates, including hormonal contraceptives, can result in decreased concentrations and reduced efficacy of CYP3A substrates.

Lactation

Because of the potential risk for serious adverse reactions from TAZVERIK in the breastfed child, advise women not to breastfeed during treatment with TAZVERIK and for one week after the final dose.

Before prescribing TAZVERIK, please read the full Prescribing Information.