On June 15, 2018 Epizyme, Inc. (NASDAQ:EPZM), a clinical-stage company developing novel epigenetic therapies, announced positive interim data from an ongoing Phase 2 study of its lead candidate tazemetostat, a potent, selective, orally available EZH2 inhibitor, as a monotherapy for patients with relapsed or refractory follicular lymphoma (FL) (Press release, Epizyme, JUN 15, 2018, View Source [SID1234527346]). The data, presented today at the 23rd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Stockholm, show that tazemetostat demonstrated meaningful clinical activity and was generally well tolerated in these heavily pre-treated patients.
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Interim data as of May 1, 2018 included 82 evaluable patients across two cohorts, prospectively assigned by EZH2 status. In the EZH2 activating mutation cohort (n=28), an objective response rate (ORR) of 71 percent was observed; 11 percent of patients achieved a complete response (CR), and 61 percent achieved a partial response (PR). Twenty-nine percent achieved stable disease (SD) as best response; of those, 21 percent are still on study with the potential to respond. All patients in this cohort experienced reduction in tumor burden, and no patients experienced progressive disease (PD) as best response. At the time of this analysis, the median progression-free survival (PFS) was 49 weeks and the median duration of response (DOR) was 32 weeks, and both endpoints continue to mature.
In the fully-enrolled cohort of FL patients with wild-type (WT) EZH2 (n=54), the ORR was 33 percent; six percent achieved a CR, and 28 percent achieved a PR. An additional 31 percent of patients achieved SD as best response, including one patient who is still receiving treatment. At the time of this analysis, the median PFS was 30 weeks and median DOR was 76 weeks. The median DOR figure continues to mature, with more than half of the responders still on therapy.
"I am impressed by the sustained clinical activity and the good tolerability of tazemetostat in this heavily pre-treated patient population. This is important for patients with relapsed or refractory follicular lymphoma, as both the response rates and durations of response usually tend to decrease with each successive line of treatment," said Gilles Salles, M.D., Ph.D., at the University Hospital of Lyon France, and president of the Lymphoma Study Association (LYSA) cooperative group. "I believe tazemetostat has the potential to fill a significant unmet need for these patients and continued investigation of tazemetostat as single agent or in combination with other agents is warranted."
*median not yet reached; data continue to mature
†includes discontinued patients with response ongoing at time of discontinuation
This ongoing global, multi-center Phase 2 study is assessing the safety and efficacy of 800 mg of tazemetostat, administered orally twice daily, in adult patients who had received at least two prior therapies. The two cohorts represented in the interim assessment included patients with an EZH2 activating mutation or those with WT EZH2. The primary endpoint is ORR, defined as CR and PR. Secondary endpoints include PFS, DOR and safety/tolerability.
Tazemetostat was generally well tolerated in this study. Interim safety results at the time of this analysis show only six percent of FL patients discontinued treatment due to treatment-related adverse events (AEs). AEs of Grade 3 or higher were reported across 17 percent of patients, the most frequent of which included thrombocytopenia, anemia, asthenia and fatigue.
"Today’s interim update underscores our belief that tazemetostat may be an important therapeutic candidate in relapsed or refractory follicular lymphoma and may play a key role in the treatment landscape, regardless of mutational status," said Robert Bazemore, president and chief executive officer of Epizyme. "The patients who are participating in this study deserve our gratitude. At Epizyme, we are dedicated to continuing our work with the global investigator community to resolve the partial clinical hold and complete enrollment in this study, in an effort to bring tazemetostat to people living with follicular lymphoma."
Investor Conference Call Reminder
Epizyme will host an investor conference call and webcast today at 8:30 a.m. EDT to discuss interim clinical activity and tolerability data from adult patients with relapsed or refractory FL who are receiving tazemetostat in the company’s ongoing Phase 2 study. To participate in the call, please dial (877) 844-6886 (domestic) or (970) 315-0315 (international) and refer to conference ID 4869637. A live webcast will be available in the investor section of the company’s website at www.epizyme.com. The webcast will be archived on the website for 60 days.
About Follicular Lymphoma (FL)
An estimated 40,000 people in the U.S. and EU5 are treated for FL each year. FL is an incurable and deadly form of cancer that is most frequently treated with multiple lines of systemic chemotherapy. As a result, there remains a significant need for an effective, convenient and tolerable medicine that patients can take for long durations.
About the Tazemetostat Clinical Trial Program
Tazemetostat, a first-in-class EZH2 inhibitor, is currently being studied as a monotherapy in ongoing Phase 1 and 2 programs in certain molecularly defined solid tumors, including epithelioid sarcoma (ES) and other INI1-negative tumors; both follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) forms of non-Hodgkin lymphoma (NHL); mesothelioma and combination studies in DLBCL