AstraZeneca, a global, innovation-driven biopharmaceutical business, has entered into a clinical trial collaboration with Peregrine Pharmaceuticals, Inc., a biopharmaceutical company, to evaluate the safety and efficacy of Peregrine’s investigational phosphatidylserine (PS)-signalling pathway inhibitor, bavituximab, in combination with AstraZeneca’s investigational anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736).

The planned phase I/Ib trial will evaluate the safety and efficacy of bavituximab in combination with durvalumab in multiple solid tumours.

AstraZeneca and Peregrine will collaborate on a non-exclusive basis to evaluate the combination of bavituximab and durvalumab with chemotherapy as a potential treatment in various solid tumours. The phase I part of the trial is expected to establish a recommended dose regimen for the combination and the phase Ib part of the trial will assess the safety and efficacy of the investigational combination. The initial trial will be conducted by Peregrine.

Bavituximab and durvalumab are investigational immunotherapies with different mechanisms that assist the body's immune system in fighting cancer. Bavituximab targets and modulates the activity of phosphatidylserine, a highly immune-suppressive molecule expressed broadly on the surface of cells in the tumour microenvironment. The treatment increases activated T-cells in tumours and fights cancer by reversing the immunosuppressive environment that many tumours establish in order to proliferate. Durvalumab is a monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumours avoid detection by the immune system. Preclinical data have demonstrated that by combining the enhanced T-cell mediated anti-tumour activity of bavituximab with checkpoint inhibitors like PD-L1 antibodies, the ability of tumour-specific T-cells to continue attacking the tumor is prolonged.

Robert Iannone, head of immuno-oncology, global medicines development at AstraZeneca said, “We believe that combination therapy in immuno-oncology has the potential to be a novel and highly effective approach to treating cancer. Our partnership with Peregrine provides the opportunity to explore an exciting, novel combination that could deliver important clinical benefit to patients across a range of cancers.”

Steven W. King, president and chief executive officer of Peregrine said, " Data generated to date have shown significant potential for combining bavituximab with agents targeting the PD-1/PDL-1 pathway and we’re excited to further explore this approach in studies with durvalumab. AstraZeneca, with its biologics arm MedImmune, is a recognised leader in the immuno-oncology field and this collaboration will play a key role as we continue to fully explore the potential of bavituximab in combination immunotherapies for a variety of clinical applications.”

Bavituximab is an investigational chimeric monoclonal antibody that targets phosphatidylserine (PS). Signals from PS inhibit the ability of immune cells to recognise and fight tumours. Bavituximab, the lead compound in Peregrine's immuno-oncology development programme, blocks PS to remove this immunosuppressive signal and sends an alternate immune activating signal. Targeting PS with bavituximab has been shown to shift the functions of immune cells in tumours, resulting in robust anti-tumour immune responses.

Durvalumab is an investigational human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumours avoid detection by the immune system. Durvalumab blocks these signals, countering the tumour's immune-evading tactics. Durvalumab is being developed, alongside other immunotherapies, to empower the patient's immune system and attack the cancer.