Clinical Trials

Date: 2018-06-03

Type of information: Presentation of results at a congress

phase: 2

Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago

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 first-in-class oral EZH2 inhibitor 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: relapsed/refractory malignant mesothelioma patients with BRCA1-associated protein 1 (BAP1) loss-of-function

Therapeutic area: Cancer - Oncology - Rare diseases

Country:

Trial details:

The Phase 2, multicenter, open-label study was designed to evaluate 800 mg of tazemetostat monotherapy administered orally twice daily in adult patients with measurable relapsed/refractory malignant mesothelioma. The trial enrolled 74 patients and was conducted in two parts: the first part enrolled patients regardless of BAP1 status (n=13) to evaluate the safety and pharmacokinetics (PK) of tazemetostat. The second part enrolled patients with BAP1 loss-of-function (n=61) to determine DCR. Secondary endpoints included overall response rate, progression-free survival, overall survival, safety, population PK and response biomarkers.

Latest news:

• On June 3, 2018, Epizyme announced the first detailed results from the Phase 2 study of tazemetostat in relapsed/refractory malignant mesothelioma patients with BRCA1-associated protein 1 (BAP1) loss-of-function. The data have been presented during a poster and subsequent discussion session at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.
The primary endpoint was met with 51 percent of patients (31/61) having achieved disease control at 12 weeks, exceeding the pre-specified disease control rate (DCR) threshold of ?35 percent. DCR is defined as complete response, partial response (PR) or stable disease. As of January 16, 2018, 16 patients (26%) had maintained disease control for ?24 weeks since starting treatment with tazemetostat, two of whom achieved PR. Patients enrolled in the study were heavily pretreated, with a median of two prior lines of therapy.
Consistent with findings from adult studies across the tazemetostat clinical development program, tazemetostat was generally well tolerated. No patients discontinued due to treatment-emergent adverse effects (TEAEs); five patients had dose reductions due to TEAEs. The five most frequently reported TEAEs (all grades) were fatigue (32%), decreased appetite (28%), dyspnea (28%), nausea (27%), and cancer pain (26%), regardless of relationship to study drug.