FDA Grants Accelerated Approval to Tazemetostat for Follicular Lymphoma

Tazemetostat, an enhancer of zeste homolog 2 (EZH2) gene inhibitor, was granted accelerated approval for two indications in adults with relapsed or refractory follicular lymphoma (FL): patients whose tumors are positive for an EZH2 mutation and who have received at least 2 prior therapies and patients who have no satisfactory alternative treatment options. The agency simultaneously approved the cobas EZH2 Mutation Test as a companion diagnostic for tazemetostat.

Approval for tazemetostat was supported by results from two open-label, single-arm cohorts (Cohort 4 – EZH2 mutated FL and Cohort 5 – EZH2 wild-type FL) of a multicenter trial in patients with histologically confirmed FL after at least 2 prior systemic therapies. Patients received tazemetostat 800 mg orally twice daily until disease progression or unacceptable toxicity. The trial’s primary endpoints were overall response rate (ORR) and duration of response (DOR).

The ORR was 69% for 42 patients with EZH2-mutation FL, with 12% achieving complete response (CR) and 57% achieving partial response (PR). Median DOR in these patients was 10.9 months (95% CI 7.2 to not estimable). In 53 patients with EZH2 wild-type FL, the ORR was 34%, with CR and PR rates of 4% and 30%, respectively. The median DOR for this group was 13 months (95% CI 5.6 to not estimable).

The most common adverse events associated with tazemetostat (occurring in ≥20% of patients) included fatigue, upper respiratory tract infection, musculoskeletal pain, nausea, and abdominal pain, with serious adverse reactions in 30% of patients. The approved starting dose is 800 mg taken orally twice daily with or without food.

Sources: FDA press release, June 18, 2020; Roche Diagnostics press release, June 19, 2020.