On 18 June 2020, tazemetostat (Tazverik), an EZH2 (Enhancer of zeste homolog 2) inhibitor, procured U.S. FDA (United States Food and Drug Administration) accelerated approval to manage adult individuals with relapsed or refractory FL (follicular lymphoma) whose tumors are harboring an EZH2 mutation as identified by an FDA-approved test and who have been administered at least two prior systemic therapies.
This novel indication may also be utilized for relapsed or refractory FL adults who have a paucity of adequate and satisfactory alternative treatment choices. The cobas EZH2 Mutation Test has also been granted FDA approval as a companion diagnostic test for tazemetostat.
The new approval was based on results from an open-label, single-arm multicenter clinical trial involving patients with histologically confirmed FL after being treated with at least two prior systemic therapies. The cohort was divided into two treatment groups: EZH2-mutated FL (n=42) and EZH2 wild-type FL (n=53). Utilizing formalin-fixed, paraffin-embedded tumor samples, EZH2 mutations were identified prospectively and were centrally tested using the cobas EZH2 Mutation Test.
Oral administration of 800 mg Tazemetostat twice daily was given to the participants until unacceptable toxicity or confirmed disease progression. According to the International Working Group Non-Hodgkin Lymphoma criteria as assessed by an independent review committee, efficacy was based on ORR (overall response rate) and duration of response.
The ORR, percentage of patients achieving a partial and complete response, and the median duration of response in patients with EZH2-mutated FL and patients with EZH2 wild-type FL are illustrated in the following table:
ORRPatients achieving a complete responsePatients achieving a partial responseMedian duration of response EZH2-mutated FL69.00%12.00%57.00%10.9 monthsEZH2 wild-type FL34.00%4.00%30.00%13 monthsFatigue, musculoskeletal pain, upper respiratory tract infection, abdominal pain, and nausea were the most commonly reported (? 20%) adverse reactions. In 30% of patients, toxic adverse reactions occurred, mostly from infection.
The most common reason for cessation of treatment (2% of patients) was the second primary malignancy. The prescribing information incorporates a precaution and warning for the occurrence of secondary malignancies. The dose of tazemetostat is suggested to be 800 mg administered orally twice daily with or without food.
Source: US FDA
Original title of the article FDA granted accelerated approval to tazemetostat for follicular lymphoma