Tazemetostat

TAZVERIK is a methyltransferase inhibitor 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. Adult patients with relapsed or refractory follicular lymphoma whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least 2 prior systemic therapies. Adult patients with relapsed or refractory follicular lymphoma who have no satisfactory alternative treatment options. These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Tazemetostat is an inhibitor of the methyltransferase, EZH2, and some EZH2 gain-of-function mutations including Y646X, A682G, and A692V. Tazemetostat also inhibited EZH1 with a half-maximal inhibitory concentration (IC 50 ) of 392 nM, approximately 36 times higher than the IC 50 for inhibition of EZH2. The most well-characterized function of EZH2 is as the catalytic subunit of the polycomb repressive complex 2 (PRC2), catalyzing mono-, di-, and trimethylation of lysine 27 of histone H3. Trimethylation of histone H3 leads to transcriptional repression. SWItch/Sucrose Non-Fermentable (SWI/SNF) complexes can antagonize PRC2 function in the regulation of the expression of certain genes of patients with epithelioid sarcoma.

Recommended dosage is 800 mg taken orally twice daily with or without food. Patient Selection Select patients with R/R FL for treatment with TAZVERIK based on the presence of EZH2 mutation of codons Y646, A682, or A692 in tumor specimens. Information on FDA-approved tests for the detection of EZH2 mutation in relapsed or refractory follicular lymphoma is available at: http://www.fda.gov/CompanionDiagnostics.

None. None.

Secondary Malignancies: TAZVERIK increases the risk of developing secondary malignancies, including T-cell lymphoblastic lymphoma, myelodysplastic syndrome, acute myeloid leukemia, and B-cell acute lymphoblastic leukemia. Monitor patients long-term for the development of secondary malignancies. Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of potential risk to a fetus and to use effective non-hormonal contraception.

The following clinically significant adverse reactions are described elsewhere in labeling: Secondary Malignancies. The most common (≥20%) adverse reactions in patients with epithelioid sarcoma are pain, fatigue, nausea, decreased appetite, vomiting, and constipation. The most common (≥20%) adverse reactions in patients with follicular lymphoma are fatigue, upper respiratory tract infection, musculoskeletal pain, nausea, and abdominal pain.

Strong or Moderate Cytochrome P450 (CYP)3A Inhibitors: Avoid coadministration of strong or moderate CYP3A inhibitors with TAZVERIK. Reduce the dose of TAZVERIK if coadministration of strong or moderate CYP3A inhibitors cannot be avoided. Strong or Moderate CYP3A Inducers: Avoid coadministration with TAZVERIK.

TAZVERIK is available in: Bottles of 240 tablets with a desiccant, NDC 72607-100-00 Do not store above 30°C (86°F).