On June 18, the U.S. Food and Drug Administration (FDA) granted accelerated approval to tazemetostat (Tazverik), an EZH2 inhibitor, for 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 two prior systemic therapies, as well as for adult patients with relapsed or refractory follicular lymphoma who have no satisfactory alternative treatment options.
The FDA also approved the cobas EZH2 Mutation Test as a companion diagnostic for tazemetostat.
Approval was based on two open-label, single-arm cohorts (cohort 4: EZH2-mutated follicular lymphoma and cohort 5: EZH2 wild-type follicular lymphoma) of a multicenter trial (Study E7438-G000-101) in patients with histologically confirmed follicular lymphoma after at least two prior systemic therapies. EZH2 mutations were identified prospectively using formalin-fixed, paraffin-embedded tumor samples, which were centrally tested using the cobas EZH2 Mutation Test.
Patients received tazemetostat at 800 mg orally twice daily until confirmed disease progression or unacceptable toxicity. Efficacy was based on overall response rate and duration of response according to the International Working Group Non-Hodgkin Lymphoma criteria as assessed by an independent review committee.
The overall response rate in 42 patients with EZH2-mutated follicular lymphoma was 69% (95% confidence interval [CI] = 53%–82%), with 12% of patients having a complete response and 57%, a partial response. Median duration of response in these patients was 10.9 months (95% CI = 7.2–not evaluable). The overall response rate in 53 patients with EZH2 wild-type follicular lymphoma was 34% (95% CI = 22%–48%), with 4% of patients having a complete response and 30%, a partial response. Median duration of response was 13 months (95% CI = 5.6–not evaluable).
The most commonly reported (≥ 20%) adverse reactions included fatigue, upper respiratory tract infection, musculoskeletal pain, nausea, and abdominal pain. Serious adverse reactions occurred in 30% of patients, most often from infection. Second primary malignancy was the most common reason for treatment discontinuation (2% of patients). The prescribing information includes a warning and precaution for secondary malignancies.
The recommended tazemetostat dose is 800 mg taken orally twice daily with or without food.