The Food and Drug Administration ( FDA ) has granted accelerated approval to Tazverik ( Tazemetostat ), an EZH2 inhibitor, for adult patients with relapsed or refractory ( R/R ) follicular lymphoma ( FL ) 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, and for adult patients with R/R follicular lymphoma who have no satisfactory alternative treatment options.
The FDA has 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 FL and Cohort 5 - EZH2 wild-type FL ) of a multi-center trial ( Study E7438-G000-101) in patients with histologically confirmed follicular lymphoma after at least 2 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 800 mg orally twice daily until confirmed disease progression or unacceptable toxicity.
Efficacy was based on overall response rate ( ORR ) and duration of response ( DOR ) according to the iwNHL ( International Working Group Non-Hodgkin Lymphoma ) criteria as assessed by an independent review committee.
ORR in 42 patients with EZH2 mutant follicular lymphoma was 69% ( 95% CI: 53%, 82% ), with 12% complete responses and 57% partial response.
Median DOR in these patients was 10.9 months ( 95% CI: 7.2, NE ).
The ORR in 53 patients with EZH2 wild-type follicular lymphoma was 34% ( 95% CI: 22%, 48% ), with 4% complete responses and 30% partial responses.
Median DOR was 13 months ( 95% CI: 5.6, NE ).
The most common ( greater than or equal to 20% ) adverse reactions in patients with follicular lymphoma included fatigue, upper respiratory tract infection, musculoskeletal pain, nausea and abdominal pain.
Serious adverse reactions occurred in 30%, 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.
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). ( Xagena )
Source: FDA, 2020