Date: 2017-06-26
Type of information: Clinical research agreement
Compound: tazemetostat - EPZ-6438 (E7438) and Tecentriq™ (atezolizumab)
Company: Epizyme (USA - MA) Genentech, a member of Roche Group (USA - CA - Switzerland)
Therapeutic area: Cancer - Oncology
Type agreement: clinical research - collaboration
Action mechanism:
- enzyme inhibitor/histone methyltransferase inhibitor/monoclonal antibody/immunotherapy product. 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.
Anti-PDL1 antibody atezolizumab (MPDL3280A) is a monoclonal antibody designed to make cancer cells more vulnerable to the body’s immune system by interfering with PD-L1. PD-L1 is found on the surface of cells in tumours and is believed to act as a “stop sign,” preventing the immune system from destroying cancer cells. By inhibiting PD-L1, MPDL3280A may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells. MPDL3280A is being studied in clinical trials to understand whether blocking PD-L1 will help the immune system respond to cancer.
Disease: relapsed or refractory diffuse large B-cell lymphoma (DLBCL), non-Hodgkin lymphoma, relapsed/refractory metastatic non-small cell lung cancer (NSCLC)
Details:
- • On June 22, 2016, Epizyme announced it has entered into a collaboration agreement with Genentech to conduct a clinical trial to investigate the anti-cancer effects of Epizyme's EZH2 inhibitor, tazemetostat, and Genentech's recently approved anti-PD-L1 cancer immunotherapy, Tecentriq™ (atezolizumab), when used in combination. The study will evaluate this combination regimen for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), the most common form of non-Hodgkin lymphoma. Under the agreement, Genentech will manage study operations for the planned clinical trial. The planned phase 1b clinical trial is expected to begin enrolling patients in the second half of 2016. "The goal of this collaboration is to generate clinical proof-of-concept for the combination, building on tazemetostat's activity as a monotherapy in a Phase 1 study of NHL and preclinical observations that EZH2 inhibition may have a priming effect on the immune system and improve the activity of checkpoint inhibitors," said Peter Ho , M.D., Ph.D., Chief Medical Officer, Epizyme . "We look forward to evaluating this combination in patients with DLBCL, and to exploring the potential to expand the therapeutic opportunities for tazemetostat, as well as Tecentriq."
Financial terms:
Latest news:
- • On June 26, 2017, Epizyme announced that it has expanded its clinical collaboration with Genentech. Under the new agreement, tazemetostat administered in combination with atezolizumab (Tecentriq®) will be evaluated in a Phase 1b/2 clinical study for the treatment of patients with relapsed/refractory metastatic non-small cell lung cancer (NSCLC). The study will be part of MORPHEUS, Genentech's open-label, multi-center, randomized umbrella study evaluating the efficacy and safety of multiple immunotherapy-based treatment combinations for metastatic NSCLC.
- Genentech will sponsor the planned Phase 1b/2 clinical trial, which is expected to be initiated by the end of 2017. It is anticipated that the study will enroll up to 40 patients who have experienced disease progression during or following treatment with a platinum-containing chemotherapy regimen and a PD?L1/PD-1 checkpoint inhibitor. Financial terms are not disclosed and Epizyme will retain global development and commercialization rights to tazemetostat.
Is general: Yes
