Clinical Trials

Date: 2016-08-11

Type of information: Treatment of the first patient

phase: 2

Announcement: treatment of the first patient

Company: Epizyme (USA - MA)

Product: tazemetostat - EPZ-6438 (E7438)

Action mechanism:

enzyme inhibitor/histone methyltransferase inhibitor. EZH2 is a histone methyltransferase (HMT) that is increasingly understood to play a potentially oncogenic role in a number of cancers. These include germinal center (GC) non-Hodgkin lymphomas, INI1-deficient cancers such as synovial sarcoma and malignant rhabdoid tumors, and a range of other solid tumors. EPZ-6438 is a small molecule inhibitor of EZH2 created with Epizyme’s proprietary product platform, for the treatment of non-Hodgkin lymphoma patients. In many human cancers, misregulated EZH2 enzyme activity results in misregulation of genes that control cell proliferation — without these control mechanisms, cancer cells are free to grow rapidly. Preclinical findings from published reports suggest that mesothelioma, and particularly mesothelioma characterized by BAP1 loss of function, may be sensitive to EZH2 inhibition. Mesothelioma characterized by BAP1 loss of function accounts for 40 to 60 percent of the approximately 12,000 new mesothelioma cases each year in major markets.
Epizyme granted Eisai a worldwide license to EPZ-6438 (Eisai refers to this therapeutic candidate as E7438), 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.

Disease: mesothelioma characterized by BAP1 loss-of-function

Therapeutic area: Cancer - Oncology

Country: France, UK, USA

Trial details:

The international, open-label, phase 2 study will evaluate tazemetostat as a monotherapy in a total of 67 patients at multiple sites in the United States , United Kingdom and France . Tazemetostat is orally administered at a dose of 800 mg twice-daily. The safety and pharmacokinetic profile of tazemetostat will first be evaluated in 12 patients with relapsed or refractory mesothelioma regardless of BAP1 status. Subsequently, a total of 55 patients with relapsed or refractory mesothelioma characterized by BAP1 loss-of-function will be treated using a two-stage study design. The primary endpoint of the study is disease control rate (complete response, partial response or stable disease) at 12 weeks. Secondary endpoints include overall response rate, progression-free survival, duration of response and overall survival. (NCT02860286)

Latest news:

• On August 11, 2016, Epizyme announced that the first patient has been dosed in the global phase 2 study evaluating tazemetostat, a first-in-class EZH2 inhibitor, for the treatment of adults with mesothelioma characterized by BAP1 loss-of-function. The company has now four registration-supporting monotherapy trials underway with tazemetostat (ongoing phase 2 programs in non-Hodgkin lymphoma), certain genetically defined solid tumors, including INI1-negative and SMARCA4-negative tumors and synovial sarcoma, and mesothelioma.
Epizyme also plans to initiate additional clinical trials of tazemetostat in 2016, including a combination with R-CHOP in collaboration with the Lymphoma Study Association and a combination with Tecentriq™ (atezolizumab) in collaboration with Genentech, both in patients with diffuse large B-cell lymphoma.
• On May 4, 2016, Epizyme announced that the FDA has accepted its Investigational New Drug (IND) application for tazemetostat for the treatment of adults with mesothelioma characterized by BAP1 loss-of-function.
Mesothelioma characterized by BAP1 loss of function accounts for 40-60 percent of the approximately 12,000 new mesothelioma cases each year in major markets.