CAMBRIDGE, Mass.—Clinical-stage biopharmaceutical company Epizyme Inc. has begun a collaboration agreement with the Lymphoma Study Association (LYSA) to investigate the potential of combining tazemetostat with R-CHOP as a front-line treatment for patients with diffuse large B cell lymphoma (DLBCL), the most common form of non-Hodgkin lymphoma.
Per the terms of the agreement, the open-label, Phase 1b/2 clinical trial of this combination therapy will be jointly conducted with the Lymphoma Academic Research Organization (LYSARC), the operational arm of LYSA. LYSARC will sponsor the study, which was jointly designed by LYSARC and Epizyme and will be conducted at multiple sites in France. Participants will consist of elderly, high-risk patients with newly diagnosed DLBCL, and will receive tazemetostat in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), a standard treatment in newly diagnosed DLBCL. Enrollment is expected to begin mid-2016.
“We are pleased to have established a collaboration with LYSA and to conduct the first investigation of tazemetostat in the front-line treatment setting,” said Robert Bazemore, president and CEO of Epizyme, said in a press release. “This study agreement aligns with Epizyme’s strategy of partnering with world-class research organizations to accelerate our development programs. The planned combination trial builds on preclinical evidence of synergy between tazemetostat and R-CHOP, and will add to what we know about the utility of tazemetostat in patients with non-Hodgkin lymphoma.”
Tazemetostat is a first-in-class EZH2 inhibitor. Abnormal EZH2 activity leads to misregulation of genes that control cell proliferation and has been linked to a variety of cancers. The compound is currently being evaluated in ongoing Phase 2 programs in both non-Hodgkin lymphoma and certain genetically defined solid tumors, including INI1-negative and SMARCA4-negative tumors and synovial sarcoma. In addition, Epizyme also intends to begin initiate additional clinical evaluations of tazemetostat this year, including a combination study with an immune checkpoint inhibitor in patients with non-Hodgkin lymphoma and a monotherapy study in adults with mesothelioma. The company intends to present initial data from its Phase 2 trial of tazemetostat in non-Hodgkin lymphoma at the June ASH Lymphoma meeting, which will include objective responses from the two DLBCL arms.
Epizyme is dedicated to its evaluation and advancement of tazemetostat. On May 4, the company announced that the U.S. Food and Drug Administration had accepted its Investigational New Drug application for tazemetostat for the treatment of adults with mesothelioma characterized by BAP1 loss of function. So far, preclinical findings seem to suggest that mesothelioma, especially mesothelioma characterized by BAP1 loss of function, may be sensitive to EZH2 inhibition. This subtype accounts for roughly 40 to 60 percent of the approximately 12,000 new cases of mesothelioma diagnosed each year.
“We are moving quickly to expand the tazemetostat clinical program into mesothelioma, adding to our ongoing studies in non-Hodgkin lymphoma and certain genetically defined solid tumors. We believe that tazemetostat has the potential to treat multiple types of cancer in patients who have limited treatment options. We look forward to starting the mesothelioma Phase 2 study later this year,” Bazemore remarked.