What information is included in the Chinese detailed instructions for tazestat

1. Common name: Tazemetostat, Tazemetostat

Product name: Tazverik, Tazverik

Other names: Tazerestat hydrobromide tablets, EPZ-6438

2. Indications

1. Epithelioid sarcoma (ES):Tazemetostat is for the treatment ofadult and pediatric patients 16 years of age and older who have metastatic or locally advanced epithelioid sarcoma (ES;soft tissue sarcoma) and are not suitable for complete resection.

2. Relapsed or refractory follicular lymphoma (FL): Tazerestat is suitable for adult patients with relapsed or refractory follicular lymphoma (FL; Non-Hodgkin lymphoma), provided that the tumor is confirmed to have EZH2 gene mutations and the patient has received at least two systemic treatments. At the same time, tazerestat is also suitable for adult patients with relapsed or refractory follicular lymphoma who have no suitable alternative treatment options.

3. Usage and dosage

1. Pre-treatment evaluation: Before using tazerestat, doctors will determine which patients with relapsed or refractory follicular lymphoma are suitable for treatment with this drug based on whether the Y646, A682 or A692 mutation of EZH2 is present in the tumor sample.

2. Recommended dose: The standard dose of tazerestat is 800 mg twice daily, which can be taken with or without food until the condition worsens or unacceptable side effects occur.

3. Dosage adjustment: If the patient experiences adverse reactions during use, the dose should be adjusted under the guidance of a doctor, including temporarily interrupting or reducing medication. The initial dose of tazerestat can be adjusted to 600 mg twice daily; if further dose reduction is required, it can be reduced to 400 mg twice daily. For patients who cannot tolerate the 400 mg twice daily dose, permanent discontinuation of the drug should be considered.

4. Adverse reactions

In clinical trials for epithelioid sarcoma, common adverse reactions (incidence rates≥20%) including: pain, fatigue, nausea, loss of appetite, vomiting, constipation, anemia and lymphopenia. In studies on follicular lymphoma, common adverse reactions (incidence ≥20%) include: fatigue, upper respiratory tract infection, musculoskeletal pain, nausea, abdominal pain, lymphopenia, hyperglycemia, leukopenia, neutropenia, thrombocytopenia and anemia.

5. Storage conditions

Tazerestat needs to be stored below30°C (86°F) to ensure its effectiveness and safety.

6. Mechanism of action

Tazerestat is an inhibitor targeting EZH2 transferase and some gain-of-function mutations (such as Y646X, A682G and A692V). Its half-maximal inhibitory concentration (IC50) is 392nM, showing an inhibitory ability against EZH1, which is 36 times that of EZH2. As the catalytic subunit of polycomb repressive complex 2 (PRC2), EZH2 is mainly responsible for catalyzing the mono-, di-, and trimethylation of histone H3 lysine 27. This methylation results in gene transcription repression.

In in vitro studies, tazerestat was able to effectively inhibitthe proliferation of B-cell lymphoma cell lines and demonstrated significant anti-tumor activity in mouse xenograft models with or without EZH2 functional mutations. The drug showed stronger inhibitory effects on lymphoma cell lines with mutated EZH2.

Reference materials:https://www.tazverik.com/