FDA Approves Tazemetostat for 2 Follicular Lymphoma Indications

The FDA has approved tazemetostat (Tazverik) for 2 distinct follicular lymphoma (FL) indications, including for adult patients with relapsed or refractory 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, as well as for adult patients with relapsed or refractory FL who have no satisfactory alternative treatment options, according to Epizyme, the agent’s developer.

The supplemental new drug application for these indications was approved under accelerated approval with a priority review based on overall response rate and duration of response observed in the company’s phase 2 clinical trial cohorts of FL patients with EZH2 mutations and wild-type EZH2. However, continued approval for these indications may be dependent upon verification and description of clinical benefit in a confirmatory trial(s).

“Follicular lymphoma remains an incurable disease, and even with the availability of new drugs in recent years, there have remained important unmet needs in the treatment of follicular lymphoma,” 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 tazemetostat for FL, said in a press release. “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.”

In the open-label, single-arm, multi-center phase 2 clinical trial, the efficacy of tazemetostat was evaluated in patients with histologically confirmed FL whose disease had progressed following at least 2 prior systemic treatment regimens. Patients were enrolled into 2 cohorts, 1 which enrolled 45 patients with EZH2 activating mutations and a second cohort which enrolled 54 patients with wild-type EZH2. All patients were treated with 800 mg of tazemetostat, administered orally twice a day.

The dual primary outcome measures were overall response rate (ORR) and duration of response (DOR) according to the International Working Group Non-Hodgkin Lymphoma (IWG-NHL) criteria (Cheson 2007) as assessed by Independent Review Committee. Median duration of follow-up was 22 months for patients with EZH2 activating mutations and 36 months for patients with wild-type EZH2.

Of the 42 evaluable patients with EZH2 activating mutations, the ORR (95% CI) was 69% (53%, 82%), with 12% of patients achieving a complete response (CR) and 57% achieving a partial response (PR). The median DOR was 10.9 months and ongoing. Moreover, of the 53 evaluable patients with wild-type EZH2, the ORR (95% CI) was 34% (22%, 48%), with 4% of patients achieving a CR and 30% achieving a PR. The median DOR was 13.0 months.

“In our view, there remains no clear standard of care in the relapsed and/or refractory FL population as not all patients benefit from today’s available therapies,” Shefali Agarwal, MD, chief medical officer of Epizyme, said in the release. “Based on this label, physicians will have the ability to use their clinical discretion to prescribe [tazemetostat] for their relapsed or refractory patients regardless of EZH2 mutational status and without regard to a specific line of treatment where other options are not satisfactory. We are grateful to the many patients, physicians and medical teams who helped bring us to this important achievement.”

Notably, serious adverse reactions, irrespective of attribution, occurred in 30% of patients receiving tazemetostat. Serious adverse reactions in ≥2% of patients were general physical health deterioration, abdominal pain, pneumonia, sepsis, and anemia. The most common (≥20%) adverse reactions observed are fatigue, upper respiratory tract infection, musculoskeletal pain, nausea and abdominal pain.

Even further, 8 patients (8%) discontinued due to an adverse reaction during the trial. There were no reported deaths during the study, and no black box warnings or contraindications.

“Despite witnessing numerous advancements for people with blood cancer over the past several years, many patients diagnosed with follicular lymphoma must still contend with relapse or recurrence as well the challenge of adverse events. For these reasons, and given that most patients manage their disease over a long time period, expanded treatment options can transform the patient experience and offer new hope,” Lymphoma Research Foundation chief executive officer, Meghan Gutierrez, said in the release.

Moving forward, Epizyme indicated that they are conducting a single global, randomized, adaptive confirmatory trial to evaluate the combination of tazemetostat with “R2” (lenalidomide [Revlimid] plus rituximab [Rituxan]) for patients with FL in the second-line or later treatment setting. The trial is anticipated to enroll approximately 500 patients with FL, stratified based on their EZH2 mutation status, and the safety run-in portion is already underway.

Reference:

Epizyme Announces U.S. FDA Accelerated Approval of TAZVERIK™ (tazemetostat) for Relapsed/Refractory Follicular Lymphoma [news release]. Cambridge, Massachusetts. Published June 18, 2020. businesswire.com/news/home/20200618005820/en/%C2%A0Epizyme-Announces-U.S.-FDA-Accelerated-Approval-TAZVERIK™. Accessed June 18, 2020.