Clinical Trials

Date: 2015-12-30

Type of information: Treatment of the first patient

phase: 2

Announcement: treatment of the first patient

Company: Epizyme (USA - MA) Eisai (Japan)

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.
• 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: genetically defined tumors including INI1-negative tumors, certain SMARCA4-negative tumors and synovial sarcomas

Therapeutic area: Cancer - Oncology

Country: Australia, Canada, Europe, USA

Trial details:    

Latest news:

• • On December 30, 2015, Epizyme announced that the first patient has been dosed in the phase 2 study of tazemetostat in adult patients with genetically defined tumors. The phase 1 dose escalation study in pediatric patients with the same tumor types is also now open for enrollment. The cancers being studied in these trials, INI1-negative tumors, certain SMARCA4-negative tumors and synovial sarcomas, are aggressive cancers that are poorly served by current treatments. The first sites activated for adult enrollment are Northwestern University , MD Anderson Cancer Center and Cincinnati Children's Hospital and the first sites activated for pediatric enrollment are the Dana Farber Cancer Institute and Cincinnati Children's Hospital. Additional study sites in the U.S. , Canada , Europe and Australia are planned to be added over the upcoming months.
• The adult phase 2 multicenter study will enroll up to 90 patients in three cohorts. The first cohort will be comprised of patients with malignant rhabdoid tumor, rhabdoid tumor of the kidney and atypical teratoid rhabdoid tumor, all of which are characterized by INI1- or SMARCA4-negativity. The second cohort will be comprised of patients with non-rhabdoid INI1-negative tumors including epithelial sarcoma, epithelioid malignant peripheral nerve sheath tumor, extraskeletal myxoid chondrosarcoma, myoepithelial carcinoma and renal medullary carcinoma. The third cohort will be comprised of patients with synovial sarcoma in which INI1 is dysregulated by a reciprocal translocation between chromosome 18 and the X chromosome. Patients will be dosed at 800 mg twice daily with tablets taken orally. The primary endpoint is overall response rate (ORR) for patients with INI1-negative tumors and progression-free survival (PFS) for patients with synovial sarcoma. Secondary endpoints include duration of response, overall survival (OS), and PFS for patients with INI1-negative tumors, as well as safety and pharmacokinetics (PK). Interim data from Epizyme\'s phase 2 study of tazemetostat in adult patients with genetically defined solid tumors are anticipated to be presented at a medical conference in late 2016.
• • On August 24, 2015, Epizyme announced the FDA has accepted the company’s investigational new drug (IND) application for tazemetostat for the treatment of adults and pediatric patients with INI1-negative tumors or synovial sarcoma. In the second half of 2015, Epizyme plans to initiate a multi-center phase 2 study in adults and a multi-center phase 1 study in children to evaluate tazemetostat in patients with relapsed or refractory INI1-negative tumors or synovial sarcoma.
• The adult phase 2 multicenter study will enroll up to 90 patients in three cohorts. The first cohort will be comprised of patients with malignant rhabdoid tumor (MRT), rhabdoid tumor of the kidney (RTK) and atypical teratoid / rhabdoid tumor (ATRT). The second cohort will be comprised of patients with other INI1-negative tumors including epithelial sarcoma, epithelioid malignant peripheral nerve sheath tumor, extraskeletal myxoid chondrosarcoma, myoepithelial carcinoma, and renal medullary carcinoma. The third cohort will be comprised of patients with synovial sarcoma. Dosing in all three cohorts will be at the recommended phase 2 dose of 800 mg twice per day (BID) with a tablet formulation, which Epizyme is also using in its ongoing phase 2 trial in non-Hodgkin lymphoma. The primary endpoint is overall response rate (ORR) for patients with INI1-negative tumors and progression-free survival (PFS) for patients with synovial sarcoma. Secondary endpoints include duration of response, overall survival (OS), PFS for patients with INI1-negative tumors, safety and pharmacokinetics (PK).
• The pediatric phase 1 multicenter study will enroll approximately 40 patients in a dose escalation design, followed by dose expansion, with an oral suspension of tazemetostat. The study will enroll subjects with INI1-negative tumors or synovial sarcoma. INI1-negative tumors include MRT, ATRT, RTK, and other INI1-negative tumors as previously described. The primary endpoint of study is safety with the objective of establishing the recommended phase 2 dose in pediatric patients. Secondary endpoints include PK, ORR, duration of response, PFS and OS.

Is general: Yes