Drug Research
Drug Discovery & Development

Innate Pharma, MedImmune enter clinical trial collaboration

Published 30 January 2018

Innate Pharma has entered into a clinical trial collaboration with MedImmune, the global biologics research and development arm of AstraZeneca.

The Phase I/II study (STELLAR-001) will evaluate the safety and efficacy of durvalumab, an anti-PD-L1 immune checkpoint inhibitor, in combination with Innate's investigational first-in-class anti-C5aR monoclonal antibody, IPH5401, as a treatment for patients with selected solid tumors.

Innate Pharma CEO Mondher Mahjoubi said: "Our collaboration with MedImmune provides further evidence of Innate's commitment to exploring the full combination potential of IPH5401 as we progress our immuno-oncology portfolio.

"We believe IPH5401 could become an important partner in PD-1/PD-L1 combination strategies."

The Phase I part of the trial is expected to establish a recommended dose regimen of IPH5401 in combination with durvalumab in selected solid tumors, and the Phase II part will assess the safety and efficacy of the combination in these patients.

The study will be conducted by Innate and the costs will be equally shared by both parties. The agreement between Innate Pharma and MedImmune is non-exclusive.

Both durvalumab and IPH5401 are cancer immunotherapies, a potent class of treatments that use the body's own immune system to help fight cancer. Durvalumab blocks PD-L1 interactions with PD-1 and CD80, countering the tumor's immune-evading tactics and inducing an immune response.

 Preclinical findings suggest that C5aR blockade increases immune-mediated tumor killing and efficacy of checkpoint inhibitors. Complement cascade factor 5a (C5a), secreted by tumor cells, attracts and stimulates C5aR-overexpressing myeloid-derived suppressor cells (MDSC) and neutrophils in the tumor microenvironment.

Part of the innate immune system, these types of cells promote tumor growth by secreting inflammatory mediators, immunosuppressive cytokines and angiogenic factors. They potently suppress T and NK cells and hamper the activities of PD-1/PD-L1 checkpoint blockers.

Innate Pharma and AstraZeneca have an existing co-development and commercialization agreement for monalizumab, a first-in-class humanized IgG4 targeting NKG2A receptors expressed on tumor infiltrating cytotoxic NK and CD8 T lymphocytes.

IPH5401 is a first-in-class fully human antibody that blocks the binding of C5a to C5a receptors (C5aR), thereby reducing the accumulation and activation of myeloid-derived suppressor cells (MDSC) and neutrophils in the tumor microenvironment.

Treatment with IPH5401 may unleash anti-tumor activities of T cells and NK cells. Preclinical experiments support development of IPH5401 in combination with PD-1/PD-L1 checkpoint blockers or other cancer immunotherapies.

Durvalumab, a human monoclonal antibody directed against PD-L1, blocks PD-L1 interaction with PD-1 and CD80 on T cells, countering the tumour's immune-evading tactics and inducing an immune response.

As part of a broad development programme, durvalumab is being investigated as monotherapy and in combination with IO, small molecules, and chemotherapies across a range of tumours and stages of disease.



Source: Company Press Release