The Food and Drug Administration (FDA) has granted accelerated approval to Tazverik™ (tazemetostat; Epizyme) for the treatment of 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 FL who have no satisfactory alternative treatment options.
The approval was based on an open-label, multicenter, phase 2 study (NCT01897571) that assessed the efficacy and safety of tazemetostat 800mg twice daily as monotherapy for adult patients with follicular lymphoma with either EZH2 activating mutations (n=45) or wild-type EZH2 (n=54), who had received at least 2 prior lines of systemic therapy. The primary end point was objective response rate (ORR); secondary end points included progression-free survival (PFS) and safety.
Findings from the study showed that tazemetostat achieved meaningful clinical activity according to the International Working Group Non-Hodgkin Lymphoma criteria as assessed by an independent review committee. Among patients with EZH2 activating mutations, the ORR was 69% (95% CI, 53-82), of which 12% achieved complete response and 57% achieved partial response. The median duration of response (DoR) and PFS were 10.9 months and 14 months, respectively.
Additionally, the ORR was 34% (95% CI, 22-48) for patients with wild-type EZH2, of which 4% achieved complete response and 30% achieved partial response. The median DoR and PFS were 13 months and 11 months, respectively.
With regard to safety, the most common treatment-emergent adverse events included fatigue, upper respiratory tract infection, musculoskeletal pain, nausea and abdominal pain. Serious adverse reactions occurred in 30% of patients who received tazemetostat, most often from infection.
“The durable responses observed with this drug are notable in the context of the safety profile and route of oral, at-home administration, and will offer an important new option for physicians as we care for patients with relapsed/refractory follicular lymphoma,” said John P. Leonard, MD, the Richard T. Silver Distinguished Professor of Hematology and Medical Oncology at Weill Cornell Medicine, an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center, and an investigator in the Phase 1b/3 confirmatory trial for Tazverik for FL.
The FDA also approved the cobas EZH2 Mutation Test (Roche Molecular Systems, Inc.) as a companion diagnostic for tazemetostat.
Tazverik, a methyltransferase inhibitor, is already indicated for the treatment of patients aged ≥16 years with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection. The product is supplied as 200mg strength tablets in 240-count bottles.
For more information visit epizyme.com.