AstraZeneca and Eli Lilly and Company (Lilly) have entered into a clinical trial collaboration to evaluate the safety and preliminary efficacy of AstraZeneca’s investigational anti-PD-L1 immune checkpoint inhibitor, MEDI4736, in combination with ramucirumab (Cyramza), Lilly’s VEGF Receptor 2 antiangiogenic cancer medicine. The planned study will assess the combination as a treatment for patients with advanced solid tumours.
The phase I study is expected to establish the safety and a recommended dosing regimen, with the potential to open expansion cohorts in various tumours of interest, for the combination of MEDI4736 and ramucirumab.
Under the terms of the agreement, the trial will be sponsored by Lilly. Additional details of the collaboration, including tumour types to be studied and financial terms, were not disclosed.
MEDI4736 is a monoclonal antibody developed by MedImmune, AstraZeneca’s global biologics research and development arm, directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumours avoid detection by the immune system. Ramucirumab is a vascular endothelial growth factor (VEGF) Receptor 2 antagonist that specifically binds and blocks activation of VEGF Receptor 2 by blocking the binding of VEGF receptor ligands VEGF-A, VEGF-C, and VEGF-D. Preclinical data indicate that combining VEGFR inhibitors with immune checkpoint blockades, such as PD-L1 targeted agents, has the potential to enhance anti-tumour activity.
Robert Iannone, Head of Immuno-oncology, Global Medicines Development at AstraZeneca, said: “We believe that combination therapy in immuno-oncology has the potential to transform the way cancer is treated. MEDI4736 is supported by a comprehensive development programme and is emerging as a cornerstone of our combination-focused immuno-oncology pipeline targeting multiple tumour types. Our collaboration with Lilly is a great addition to our programme and provides the opportunity to explore another exciting, novel combination that could deliver important clinical benefit to cancer patients.”
“The development of immune checkpoint inhibitors has been one of the more exciting research advancements in recent oncology history, but it is going to be even more interesting to see how these inhibitors can be combined with other proven targeted therapies,” said Richard Gaynor, M.D., senior vice president, product development and medical affairs, Lilly Oncology. “This collaboration represents the next wave of immuno-oncology research by bringing together two innovative medicines – Lilly’s Cyramza and AstraZeneca’s MEDI4736 – as a novel combination that we hope will one day provide new cancer treatment solutions.”
In the EU, ramucirumab has been granted marketing authorisation for use in adults, in combination with paclitaxel, for the treatment of advanced gastric or gastro-oesophageal junction adenocarcinoma following prior chemotherapy, and as a monotherapy in this setting for patients for whom treatment in combination with paclitaxel is not appropriate.
Ramucirumab is approved in the US for use as a single agent or in combination with paclitaxel as a treatment for people with advanced or metastatic gastric (stomach) or gastroesophageal junction (GEJ) adenocarcinoma whose cancer has progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy. It is also approved in the US in combination with docetaxel as a treatment for people with metastatic non-small cell lung cancer (NSCLC) whose cancer has progressed on or after platinum-based chemotherapy. Additionally, it is approved in the US with FOLFIRI as a treatment for people with metastatic colorectal cancer (mCRC) whose cancer has progressed on or after therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.
MEDI4736 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. MEDI4736 blocks these signals, countering the tumour’s immune-evading tactics.