Date: 2015-08-05
Type of information: Clinical research agreement
Compound: durvalumab (MEDI4736), in combination with mocetinostat
Company: AstraZeneca (UK) Mirati Therapeutics (USA - CA)
Therapeutic area: Cancer - Oncology
Type agreement: clinical research
Action mechanism: monoclonal antibody/immune checkpoint inhibitor/HDAC inhibitor/histone deacetylase inhibitor. Durvalumab (MEDI4736) is a human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumours avoid detection by the immune system. MEDI4736 blocks these signals, countering the tumour’s immune-evading tactics.This antibody is directed against B7-H1, have been shown to block the interaction between B7-H1 and its receptors, PD-1 and CD80 (B7-1). This blockade may help to overcome the immunosuppressive effects of B7-H1 on anti-tumor T cells. Durvalumab was accelerated into Phase III clinical development in non-small cell lung cancer and head and neck cancer. The OCEANS clinical development programme will evaluate durvalumab as monotherapy and in combination with a cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) monoclonal antibody tremelimumab, in lung cancer, across the spectrum of the disease. In head and neck cancer, durvalumab is being investigated in three late stage studies (HAWK, CONDOR and EAGLE) as monotherapy and in combination with tremelimumab, looking at patients with different PD-L1 expression status who have failed on chemotherapy. A comprehensive development programme for durvalumab is underway across multiple tumor types, including gastric, pancreatic and bladder cancer, in addition to lung and head and neck cancers. Mocetinostat is an orally-bioavailable, spectrum-selective HDAC (histone deacetylase) inhibitor. Mocetinostat has completed 13 clinical trials in more than 400 patients with a variety of hematologic malignancies and solid tumors. Mirati is currently conducting Phase 2 studies of mocetinostat as a single agent in patients with bladder cancer and DLBCL. Mocetinostat is also in a Phase 2 dose confirmation study in combination with Vidaza® as treatment for intermediate and high-risk myelodysplastic syndrome (MDS).
Disease: non-small cell lung cancer (NSCLC)
Details: * On August 5, 2015, AstraZeneca announced that MedImmune, its global biologics research and development arm, has entered into an exclusive clinical trial collaboration with Mirati Therapeutics, 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-PDL1 immune checkpoint inhibitor, durvalumab (MEDI4736), in combination with mocetinostat, Mirati’s investigational spectrum-selective histone deacetylase (HDAC) inhibitor. This novel combination will initially be evaluated in patients with non-small cell lung cancer (NSCLC), with the potential to explore additional indications in the future. Durvalumab is designed to counter the tumour’s immune-evading tactics by blocking a signal that helps tumours 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 tumour immunity. Under the terms of 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.
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