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Phase 1 Dose Escalation Data for Epizyme EZH2 Inhibitor EPZ-6438 (E7438) Shows Single Agent Activity in B-Cell Non-Hodgkin Lymphomas and Malignant Rhabdoid TumorBARCELONA, Spain --(Business Wire)-- Epizyme, Inc. (NASDAQ: EPZM), a clinical stage biopharmaceutical company creating innovative personalized therapeutics for patients with genetically defined cancers, today announced results from the Phase 1 dose escalation study of the investigational EZH2 inhibitor EPZ-6438 (referred to as E7438 by Eisai) administered orally as a single agent in patients with advanced solid tumors and B-cell non-Hodgkin lymphomas. These data will be presented today at 12:10 p.m. CET/6:10 a.m. ET by EORTC Scientific Chair Jean-Charles Soria, M.D., Ph.D., on behalf of study investigator Vincent Ribrag, M.D., both of the Institut Gustave Roussy, at the 26th Annual EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics. The slides will be posted to the Epizyme website, www.epizyme.com, before the Company's conference call. "The single agent activity seen with EPZ-6438 in both non-Hodgkin lymphoma patients and the malignant rhabdoid tumor patient in this Phase 1 study is very encouraging," said Professor Ribrag. "This is true particularly given the advanced nature of disease and the extent of prior treatment failures in many of these patients." This open-label, multicenter, Phase 1 study investigated EPZ-6438 as a single agent in patients with advanced B-cell non-Hodgkin lymphomas (diffuse large B-cell lymphoma = 6, follicular lymphoma = 5, marginal zone lymphoma = 1) or advanced solid tumors (colorectal = 4, INI1-deficient malignant rhabdoid tumor = 1, INI1-deficient synovial sarcoma = 1, other solid tumors = 6). The study objectives included establishment of the maximum tolerated or recommended Phase 2 dose, safety, tolerability, pharmacokinetics and preliminary evaluation of anti-tumor activity. Patients on study were heavily pre-treated, with fourteen patients having received between two and four prior therapies and nine having received more than four prior therapies. Five dosing cohorts were studied: 100 mg (n=6), 200 mg (n=3), 400 mg (n=3), 800 mg (n=6) and 1600 mg (n=6). As of October 20, 2014, the following activity was observed in the 20 patients with advanced B-cell NHL or advanced solid tumors who were evaluable for efficacy:
"These results provide encouraging evidence of anti-tumor activity with EPZ-6438, in both NHL and malignant rhabdoid tumors, including the potential for responses to improve with continued treatment," said Peter Ho, M.D., Ph.D., Chief Deveopment Officer, Epizyme. "Given the clinical activity we saw in both wild type EZH2 and non-germinal center lymphoma patients, our plan for the first Phase 2 NHL study is to evaluate EPZ-6438 in DLBCL and FL patients with and without EZH2 mutations." All 24 patients were evaluated for safety and tolerability as of the safety data cut-off of September 24, 2014. Twenty of 24 patients were evaluable for efficacy as of October 20, 2014. EPZ-6438 was administered orally, twice daily in 28-day cycles to all patients. The majority of adverse events were Grade 1 or Grade 2. Adverse events occurring in more than 10 percent of patients were asthenia, decreased appetite and nausea. The only Grade 3 or Grade 4 treatment-related adverse event observed was Grade 4 thrombocytopenia in one patient at 1600 mg, which met the criteria for a dose-limiting toxicity. No AEs required treatment withdrawal or dose reduction; however, three AEs resulted in dose interruption. EPZ-6438 was rapidly absorbed and eliminated, with a terminal half-life of three to six hours. In addition, H3K27Me3 inhibition in the skin, a marker of biologic activity, was correlated to treatment exposure, with near maximal inhibition predicted by pharmacokinetic exposure at 800 mg. Among patients with non-Hodgkin lymphoma, clinical activity of EPZ-6438 did not require mutation within EZH2, as confirmatory sequencing showed all subjects evaluable for efficacy and analyzed for EZH2 were wild type. In addition, four of the five evaluable DLBCL patients had lymphoma of non-germinal center origin, and responses were observed in both germinal and non-germinal center subtypes. Currently, a Phase 2 dose of 800 mg BID is under consideration. A final recommendation for the Phase 2 dose will be approved by the Data Monitoring Committee based on efficacy, safety, and PK/PD parameters.
Conference Call and Webcast To participate in the conference call, please dial 1-877-844-6886 (domestic) or 1-970-315-0315 (international) and refer to conference ID 35051953. The live webcast can be accessed under "Events and Presentations" in the Investor Relations section of the Company's website at www.epizyme.com. Slides will be available on the Company's website prior to the conference call.
About EZH2 Cancers
About EPZ-6438 Epizyme granted Eisai a worldwide license to EPZ-6438, subject to Epizyme's right to opt in for co-development, co-commercialization and profit share arrangement with Eisai in the United States. Epizyme is working with Roche and Eisai to develop a companion diagnostic to identify patients with non-wild type EZH2, where EZH2 contains point mutations. Additional information about these partnerships may be found here: http://www.epizyme.com/about-us/partnerships/ EPZ-6438 is the second HMTi to enter human clinical development (following Epizyme's DOT1L inhibitor, EPZ-5676). Additional information about this program, including clinical trial information, may be found here: http://clinicaltrials.gov/ct2/show/NCT01897571?term=7438&rank=1
About Epizyme, Inc. For more information, visit www.epizyme.com and connect with us on Twitter (News - Alert) at @EpizymeRx.
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