MedImmune, the biologics arm of AstraZeneca, has entered into an exclusive clinical trial collaboration with Mirati Therapeutics, Inc., an oncology company focusing on genetic and epigenetic drivers of cancer. The Phase I/II study will evaluate the safety and efficacy of MedImmune's investigational anti-programmed cell death ligand 1 (PD-L1)  immune checkpoint inhibitor, durvalumab (MEDI4736), in combination with mocetinostat, Mirati's investigational spectrum-selective histone deacetylase (HDAC) inhibitor.This combination will initially be evaluated in patients with non-small cell lung cancer, with the potential to explore additional indications in the future.

Under the agreement, Mirati will conduct and fund the initial Phase I/II clinical trial, which is expected to start in 2016, and MedImmune will supply durvalumab for the trial. The parties have established a Joint Steering Committee to oversee the trial. In the event that the initial clinical trial demonstrates positive results, MedImmune will have an exclusive period of time in which to negotiate a commercial license for the combination in this indication.

Durvalumab is designed to counter the tumor's immune-evading tactics by blocking a signal that helps tumors avoid detection while mocetinostat selectively inhibits Class I HDAC enzymes, which has the potential to enhance the positive effect of checkpoint inhibitors, such as durvalumab, on tumor immunity. Durvalumab is an investigational human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumors avoid detection by the immune system. Durvalumab blocks these signals, countering the tumor's immune-evading tactics. Durvalumab is in Phase III clinical development in non-small cell lung cancer and head and neck cancer.

Mocetinostat is an orally bioavailable, spectrum-selective HDAC inhibitor. Mocetinostat is currently in two single-agent Phase II trials evaluating the treatment of patients that carry inactivating mutations of the histone acetyltransferase genes CREBBP and EP300. One trial is in patients with bladder cancer, and the other is an investigator-sponsored study in patients with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma. The US Food and Drug Administration granted orphan drug designation to mocetinostat as a treatment for DLBCL. Mirati retains worldwide rights to mocetinostat with the exception of certain Asian territories where the program is partnered with Taiho Pharmaceutical Co., Ltd.

Source: AstraZeneca