Date: 2017-10-27
Type of
information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the 2017 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics
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.
- 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: pediatric patients with relapsed or refractory INI1-negative molecularly defined solid tumors
Therapeutic
area: Cancer - Oncology
Country: Australia, Canada, Denmar, France, Germany, Italy, The Netherlands, UK, USA
Trial
details:
- The open-label, multi-dose, multi-center Phase 1 dose escalation study was conducted in 46 patients aged six months to 21 years with INI1-negative tumors including epithelioid sarcoma, poorly differentiated chordoma, atypical teratoid rhabdoid tumors, malignant rhabdoid tumors, renal medullary carcinoma or relapsed/refractory synovial sarcoma. The oral suspension of tazemetostat was administered twice daily in continuous 28-day cycles in the following cohorts: 240mg/m2, 300mg/m2, 400mg/m2, 520mg/m2, 700mg/m2, 900mg/m2, 1200mg/m2. (NCT02601937)
Latest
news:
- • On October 27, 2017, Epizyme announced data from the dose escalation portion of the company's ongoing Phase 1 clinical trial of tazemetostat pediatric patients with relapsed or refractory INI1-negative molecularly defined solid tumors. These data have been presented at the 2017 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, which is being held Oct. 26-30, 2017 in Philadelphia. The data, which are being presented by principal investigator Susan N. Chi, M.D., Director, Pediatric Brain Tumor Clinical Trials Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, and Assistant Professor of Pediatrics, Harvard Medical School, are the first presentation of tazemetostat results in pediatric patients, providing continued evidence for tazemetostat’s activity in INI1-negative tumors, as seen in adult patients.
- Tazemetostat was generally well-tolerated at all explored doses, including the highest dose tested. Adverse events (AEs) reported, regardless of attribution, were mostly mild to moderate, the most common of which were vomiting (41%), pyrexia (28%), headache (24%) and nausea (24%). Only one patient experienced a dose-limiting toxicity (DLT) event at the dose level of 300mg/m2 (Grade 4 dyspnea and Grade 3 hypoxia); however, no other DLTs were observed at higher doses. One other patient discontinued the study due to a treatment-related AE, and five patients had dose reductions.
- Tazemetostat showed encouraging anti-tumor activity across a range of INI1-negative cancers in pediatric patients. Complete or partial responses were observed in patients at dose levels ranging from 520 to 900 mg/m2 twice daily, as follows:
- Complete responses in epithelioid sarcoma (n=1), chordoma (n=1), atypical teratoid rhabdoid tumor (n=1)
- Partial response in chordoma (n=1)
- The recommended Phase 2 dose of 1200 mg/m2 twice daily was established based on safety, pharmacokinetics, pharmacodynamics and activity. The study is now enrolling patients into four dose expansion cohorts.
Is
general: Yes
