On 18 June 2020, the US Food and Drug Administration (FDA) granted accelerated approval to tazemetostat (TAZVERIK, Epizyme, Inc.), an EZH2 inhibitor, for adult patients with relapsed or refractory (R\/R) follicular lymphoma (FL) whose tumours 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 FL who have no satisfactory alternative treatment options.<\/p>\n
The FDA also approved the cobas EZH2 Mutation Test (Roche Molecular Systems, Inc.) as a companion diagnostic for tazemetostat.<\/p>\n
Approval was based on two open-label, single-arm cohorts (Cohort 4 – EZH2 mutated FL and Cohort 5 – EZH2 wild-type FL) of a multicentre trial (Study E7438-G000-101, NCT01897571) in patients with histologically confirmed FL after at least 2 prior systemic therapies. EZH2 mutations were identified prospectively using formalin-fixed, paraffin-embedded tumour samples, which were centrally tested using the cobas\u00ae EZH2 Mutation Test. Patients received tazemetostat 800 mg orally twice daily until confirmed disease progression or unacceptable toxicity.<\/p>\n
Efficacy was based on overall response rate (ORR) and duration of response (DoR) according to the International Working Group Non-Hodgkin Lymphoma criteria as assessed by an independent review committee. The ORR in 42 patients with EZH2 mutant FL was 69% (95% confidence interval [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 FL was 34% (95% CI 22%, 48%), with 4% complete responses and 30% partial responses. Median DoR was 13 months (95% CI 5.6, NE).<\/p>\n
The most common (\u226520%) 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.<\/p>\n
The recommended tazemetostat dose is 800 mg taken orally twice daily with or without food.<\/p>\n
Full prescribing information for TAZVERIK is available here<\/a>.<\/p>\n These indications are approved under accelerated approval based on ORR and DoR. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).<\/p>\n This application was granted priority review and Fast Track designation.<\/p>\n Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA\u2019s MedWatch Reporting System.<\/p>\n For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA\u2019s Oncology Center of Excellence<\/a> Project Facilitate<\/a>.<\/p>\n