Tazverik (tazemetostat) - 2 indications

Scroll down for more information on each indication:

• for patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection; approved January 2020
• for adults with EZH2 mutation positive relapsed or refractory (R/R) follicular lymphoma (FL) and R/R FL with no satisfactory alternative treatment options; approved June of 2020

General Information

Tazverik (tazemetostat) blocks activity of the EZH2 methyltransferase, which may help keep the cancer cells from growing.

Tazverik is specifically indicated for the following:

• 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 FL whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least two prior systemic therapies
• adult patients with relapsed or refractory FL who have no satisfactory alternative treatment options

Tazverik is supplied as a tablet for oral administration. The recommended dose is 800 mg orally twice daily with or without food until disease progression or unacceptable toxicity. Swallow tablets whole. Do not take an additional dose if a dose is missed or vomiting occurs after Tazverik, but continue with the next scheduled dose.

Mechanism of Action

Tazverik (tazemetostat) is a potent, selective, and orally bioavailable small-molecule inhibitor of EZH2 enzymatic activity. EPZ-6438 induces apoptosis and differentiation specifically in SMARCB1-deleted MRT cells.

Side Effects

Adverse effects associated with the use of Tazverik in patients with epithelioid sarcoma may include, but are not limited to, the following:

• pain
• fatigue
• nausea
• decreased appetite
• vomiting
• constipation

Adverse effects associated with the use of Tazverik in patients with follicular lymphoma may include, but are not limited to, the following:

• fatigue
• upper respiratory tract infection
• musculoskeletal pain
• nausea
• abdominal pain

Indication 1 - for patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection

approved January 2020

Clinical Trial Results

The FDA approval of Tazverik for epithelioid sarcoma was based on the results of a clinical trial enrolling 62 patients with metastatic or locally advanced epithelioid sarcoma. During the clinical trial, patients received 800 milligrams (mg) of Tazverik twice a day until the disease progressed or the patient reached an unacceptable level of toxicity. Tumor response assessments were performed every eight weeks during the clinical trial. The trial measured how many patients experienced complete or partial shrinkage (by a certain amount) of their tumors during treatment (overall response rate). The overall response rate was 15%, with 1.6% of patients having a complete response and 13% having a partial response. Of the nine patients that had a response, six (67%) patients had a response lasting six months or longer.

Indication 2 - for adults with EZH2 mutation positive relapsed or refractory (R/R) follicular lymphoma (FL) and R/R FL with no satisfactory alternative treatment options

approved June of 2020

Clinical Trial Results

The FDA approval of Tazverik for follicular lymphoma was based on an open-label, single-arm, multi-center Phase 2 clinical trial in patients with histologically confirmed FL whose disease had progressed following at least two prior systemic treatment regimens. Patients were enrolled into two cohorts: one cohort enrolled 45 patients with EZH2 activating mutations and a second cohort enrolled 54 patients with wild-type EZH2. All patients were treated with 800 mg of tazemetostat, administered orally twice a day. The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR). Among the 45 FL patients with an EZH2 activating mutation who received Tazverik and treated with at least 2 prior systemic therapies, the ORR was 69%, with 12% of patients achieving a complete response and 57% achieving a partial response. The median DOR was 10.9 months and ongoing. Among the 54 FL patients with wild-type EZH2 who received Tazverik and treated with at least 2 prior systemic therapies, the ORR was 34%, with 4% of patients achieving a complete response and 30% achieving a partial response. The median DOR was 13.0 months.