On December 30, 2015 Epizyme, Inc. (NASDAQ: EPZM), a clinical stage biopharmaceutical company creating novel epigenetic therapies for cancer patients, reported that the first patient has been dosed in the phase 2 study of tazemetostat in adult patients with genetically defined tumors (Press release, Epizyme, DEC 30, 2015, View Source [SID:1234508645]). Schedule your 30 min Free 1stOncology Demo! 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.
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"Life-threatening rare tumors such as rhabdoid tumors, epithelioid sarcomas and synovial sarcomas affect children and young adults who are in need of novel effective therapies since the standard approaches are only marginally useful," said George Demetri, M.D., Director, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute and Professor of Medicine, Harvard Medical School. "We are enthusiastic about evaluating tazemetostat in our patients with these forms of sarcomas since the molecular mechanism is so compelling, especially with the recent identification of mutations in INI1 or SMARCA4 as genetic drivers for these cancers."
"This important study will enroll children with cancers such as malignant rhabdoid tumor, based on unique genetic defects that appear to result in biological sensitivity to EZH2 inhibition," said Susan Chi, M.D., Director of the Pediatric Brain Tumor Clinical Trials Program, Dana-Farber Cancer Institute and Assistant Professor of Pediatrics, Harvard Medical School. "For children with these deadly diseases, tazemetostat potentially represents a meaningful option when other treatments have been exhausted."
"Initiation of the clinical program in genetically defined solid tumors is an important milestone for Epizyme and expands tazemetostat development beyond non-Hodgkin lymphoma," said Peter Ho, M.D., Ph.D., Chief Medical Officer, Epizyme. "We are excited to advance the study of tazemetostat in these patients."
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).
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 patients with the same INI1-negative tumors, SMARCA4-negative tumors or synovial sarcoma as in the adult study. The primary endpoint of the study is safety, with the objective of establishing the recommended phase 2 dose in pediatric patients. Secondary endpoints include pharmacokinetics, objective response rate, duration of response, progression free survival, and overall survival.
INI1-negative or certain SMARCA4-negative tumors are characterized as aggressive cancers with few to no approved treatments today. For example, current treatment of malignant rhabdoid tumors, an INI1-negative tumor, consists of surgery, chemotherapy and radiation therapy, which are associated with limited efficacy and significant treatment-related morbidity. In August, the FDA’s Division of Oncology Products 2 accepted Epizyme’s IND application to study adult and pediatric patients with INI1-negative solid tumors or synovial sarcoma in the U.S.
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.
About EZH2 in Cancer
EZH2 is a histone methyltransferase (HMT) that is increasingly understood to play a potentially oncogenic role in a number of cancers. These include non-Hodgkin lymphoma, INI1-negative or certain SMARCA4-negative cancers such as malignant rhabdoid tumors and epithelioid sarcomas, synovial sarcoma, and a range of other solid tumors.
About Tazemetostat
Epizyme is developing tazemetostat for the treatment of patients with non-Hodgkin lymphoma and for patients with INI1-deficient solid tumors. Tazemetostat is a first-in-class small molecule inhibitor of EZH2 created by Epizyme using its proprietary product platform. In some human cancers, aberrant EZH2 enzyme activity results in misregulation of genes that control cell proliferation resulting in the rapid and unconstrained growth of tumor cells. Tazemetostat is the WHO International Non-Proprietary Name (INN) for compound EPZ-6438.
Additional information about this program, including clinical trial information for the adult five -arm NHL study, can be found here: View Source
Clinical trial information for the adult INI1-negative tumors, certain SMARCA4-negative tumors or synovial sarcoma trial can be found here: View Source
Clinical trial information for the pediatric INI1-negative tumors, certain SMARCA4-negative tumors or synovial sarcoma trial can be found here: View Source