Tazverik
Epithelioid sarcoma — metastatic or locally advanced, not eligible for complete resection, in adults and pediatric patients ≥16 years; Relapsed or refractory follicular lymphoma (FL) — with EZH2 mutation (in combination with lenalidomide + rituximab) or after ≥2 prior systemic therapies; FL — in combination with lenalidomide + rituximab for relapsed/refractory FL regardless of EZH2 status.
Epithelioid sarcoma: 800 mg orally twice daily
FL (with len/ritux): 800 mg orally twice daily
FL (monotherapy): 800 mg orally twice daily
Swallow tablets whole with or without food
Dose reductions: 600 mg BID, then 400 mg BID
Tablets: 200 mg
None listed.
- Secondary Malignancies: Including T-cell lymphoblastic lymphoma, myelodysplastic syndrome, AML (3.1%). Monitor CBCs. Risk may increase with longer duration.
- Myelosuppression: When used with lenalidomide: Grade 3-4 neutropenia in 42%. Monitor CBC.
- Infections: Serious infections in 8%. Monitor and treat promptly.
- Embryo-Fetal Toxicity: Avoid pregnancy during and for 6 months after treatment.
Fatigue (36%), nausea (24%), musculoskeletal pain (20%), constipation (15%), upper respiratory tract infection (15%), diarrhea (14%), decreased appetite (11%), weight decrease (10%), headache (9%)
Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.
Tazemetostat is a selective inhibitor of EZH2 (Enhancer of Zeste Homolog 2), the catalytic subunit of the polycomb repressive complex 2 (PRC2). EZH2 is a histone methyltransferase that trimethylates histone H3 at lysine 27 (H3K27me3), leading to transcriptional silencing. Gain-of-function mutations in EZH2 (common in FL) or loss of INI1/SMARCB1 (in epithelioid sarcoma) result in aberrant H3K27 trimethylation and epigenetic silencing of tumor suppressors. By inhibiting EZH2, tazemetostat restores expression of silenced genes involved in cell differentiation and tumor suppression.
Tmax: 1-2 hours. Half-life: approximately 17 hours (range 14-27h). Protein binding: ~96%. Metabolized by CYP3A. Steady-state by Day 7. Excreted in feces (80%) and urine (11%).
Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.
- EZH-202 — Tazemetostat in relapsed/refractory follicular lymphoma with EZH2 mutation. Phase II, n=99.