FDA Grants Accelerated Approval to Tazemetostat for Follicular Lymphoma
On June 18, 2020, the U.S. Food and Drug Administration (FDA) granted accelerated approval (https://www.fda.gov/drugs/fda-granted-accelerated-approval-tazemetostat-follicular-lymphoma) to tazemetostat (Tazverik™), an EZH2 inhibitor, for adult patients with relapsed or refractory follicular lymphoma (FL) whose tumors are positive for an EZH2 mutation, as detected by an FDA-approved test, who have received at least two prior systemic therapies and have no satisfactory alternative treatment options.
FDA also approved the cobas® EZH2 Mutation Test as a companion diagnostic for tazemetostat.
Approval was based on two open-label, single-arm cohorts (one with EZH2 mutated FL and a second cohort with EZH2 wild-type FL) of a multicenter trial (study E7438-G000-101; NCT01897571) in patients with histologically confirmed FL after at least two prior systemic therapies. FDA identified EZH2 mutations prospectively using formalin-fixed, paraffin-embedded tumor samples, which were centrally tested using the 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 international working group non-Hodgkin lymphoma criteria as assessed by an independent review committee. ORR in 42 patients with EZH2 mutant FL was 69% (95% CI = 53%, 82%), with 12% complete responses and 57% partial responses, and median DoR was 10.9 months (95% CI = 7.2, not evaluated). ORR in 53 patients with EZH2 wild-type FL was 34% (95% CI = 22%, 48%), with 4% complete responses and 30% partial responses, and median DoR was 13 months (95% CI = 5.6, not evaluated).
The most common adverse reactions (≥ 20%) were 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 orally twice daily.
FDA approved the indication under accelerated approval based on ORR and DoR. Continued approval for the indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
FDA granted the application priority review and fast track designations. A description of FDA expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics).
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.
For assistance with single-patient oncology investigational new drug applications, contact the Oncology Center of Excellence’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).