Epizyme has reported recent updates from its clinical-stage programs with the company’s lead candidate, tazemotostat, for the treatment of hematological malignancies and genetically defined solid tumors.
Tazemotostat, a first-in-class small molecule, oral EZH2 inhibitor, is now being evaluated in a global Phase 2 study (NCT02860286) for the treatment of adults with mesothelioma characterized by BAP1 loss-of-function, a mutation seen in 40 to 60 percent of patients with this life-threatening cancer.
The study is divided into two parts. In Part 1, 12 patients with relapsed or refractory malignant mesothelioma regardless of BAP1 status will be treated with a single dose of tazemetostat to assess its pharmacokinetics. In Part 2, patients with BAP1-mutated relapsed or refractory malignant mesothelioma will receive oral tazemetostat twice daily until disease progression, unacceptable toxicity, or the end of the study.
The study’s primary endpoint is disease control rate. Secondary endpoints include safety parameters, overall response rate, progression-free survival, and overall survival.
Epizyme is currently enrolling patients in the clinical trial, marking the expansion of tazemetostat development as a single therapy into a new cancer indication.
Epizyme is also evaluating tazemetostat in Phase 2 studies in non-Hodgkin’s lymphoma (NHL) and genetically defined solid tumors, with safety, effectiveness, and biomarker results expected by early next year.
The company is also preparing for regulatory meetings with the U.S. Food and Drug Administration (FDA), planned for mid-2017, to determine registration paths for its NHL program and its genetically defined solid tumor program in adult patients.
Under a collaboration with Genentech, tazemetostat is also being evaluated in a Phase 1b trial in combination with Tecentric (atezolizumab) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
In addition, tazemetostat is being assessed in a Phase 1b/2 clinical trial (NCT02889523) in combination with the chemotherapy regimen R-CHOP as a first-line treatment option for elderly patients with DLBCL.
Epizyme has entered into Cooperative Research and Development Agreements (CRADAs) with the National Cancer Institute (NCI) to evaluate tazemetostat in multiple cancer indications as well as to evaluate pinometostat, the company’s novel DOT1L inhibitor in multiple combination regimens.
In addition, Epizyme is collaborating with Foundation Medicine to support patient identification and enrollment in a Phase 2 study of tazemetostat in patients with non-Hodgkin’s lymphoma.
“Throughout 2016, we have made substantial progress toward achieving our vision, which includes advancing the clinical development of tazemetostat and expanding its therapeutic benefit into new indications and treatment settings,” Robert Bazemore, Epizyme’s president and CEO, said in a press release.
“We are executing on a broad clinical program for tazemetostat based on its early clinical activity and safety profile, and guided by strong scientific rationale. We expect 2017 to be an important year for Epizyme, led by data from the Phase 2 studies in non-Hodgkin lymphoma and genetically defined solid tumors in the first half of the year, and determination of our potential registration pathways beginning mid-year.”
Tazemetostat (EPZ-6438) is a selective inhibitor of the histone methyltransferase EZH2, frequently over-expressed in a wide variety of cancerous tissue types. Although the mechanistic contributions of EZH2 to cancer progression remain unknown, studies suggest that EZH2 mediates epigenetic modifications in cancer cells that halt the production of proteins that function as tumor suppressors.