FDA Approval Insights: Tazemetostat in Relapsed/Refractory Follicular Lymphoma

Welcome to a very special edition of OncLive^® On Air! I’m your host today, Caroline Seymour.

OncLive^® On Air is a podcast from OncLive, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

Today, we had the pleasure of speaking with John P. Leonard, MD, associate dean for clinical research and Richard T. Silver Distinguished Professor of Hematology and Medical Oncology, of Meyer Cancer Center at Weill Cornell Medicine and NewYork-Presbyterian Hospital, to discuss the FDA approval of tazemetostat (Tazverik) in follicular lymphoma.

On June 18, 2020, the FDA granted an accelerated approval to tazemetostat for the treatment of patients with relapsed/refractory follicular lymphoma whose tumors are EZH2 positive as detected by the cobas EZH2 Mutation Test and who have received at least 2 prior systemic therapies, as well as those with relapsed/refractory disease who have no other available satisfactory treatment options. The approval was based predominantly on updated results from an ongoing phase 2 trial (NCT01897571), which showed that the first-in-class EZH2 inhibitor led to an objective response rate (ORR) of 69% in patients with EZH2-mutant disease and a 34% ORR for those with wild-type EZH2 disease. The complete response and partial response rates were 12% and 57%, respectively, in those with EZH2 mutations and 4% and 30%, respectively, for patients with wild-type EZH2.

In terms of safety, the most common adverse effects (AEs) with tazemetostat were fatigue, upper-respiratory tract infection, musculoskeletal pain, nausea, and abdominal pain. Serious AEs were reported in 30% of patients, primarily due to infection. Second primary malignancy, which was the most common reason for treatment discontinuation, was reported in 2% of patients.

An international, adaptive trial will evaluate the combination of tazemetostat with lenalidomide (Revlimid) in combination with rituximab (Rituxan) in patients with follicular lymphoma in patients who have received at least 1 prior line of therapy. The study, which will be used to support a full approval for tazemetostat in this indication, is expected to enroll approximately 500 patients with follicular lymphoma, wherein patients will be stratified by EZH2 mutation status.

Follicular lymphoma is typically an incurable disease, and one in which patients will see a number of treatments over the course of their lifespan. However, novel therapies are needed for patients who progress through chemotherapy and other available options, said Leonard. The approval of tazemetostat provides another agent for this subset of patients who would have otherwise not had good options, he added.

In our exclusive interview, Leonard shared the significance of the FDA approval of tazemetostat in follicular lymphoma.