AstraZeneca, Lilly Partner in ImmunoncologyBy
AstraZeneca and Eli Lilly and Company have formed 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 Eli Lilly’s Cyramza (ramucirumab), a vascular endothelial growth factor (VEGF) VEGF Receptor 2 antiangiogenic cancer medicine. The planned study will assess the combination as a treatment for patients with advanced solid tumors.
The Phase I study is expected to establish the safety and a recommended dosing regimen, with the potential to open expansion cohorts in various tumors of interest, for the combination of MEDI4736 and ramucirumab. Under the agreement, the trial will be sponsored by Lilly. Additional details of the collaboration, including tumor 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 tumors avoid detection by the immune system. Ramucirumab is a 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-tumor activity.
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 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 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 whose cancer has progressed on or after therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine. In the EU, ramucirumab has been granted marketing authorization 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.There are several additional studies underway or planned to investigate ramucirumab as a single agent and in combination with other anti-cancer therapies for the treatment of multiple tumor types.
MEDI4736 was accelerated into Phase III clinical development in non-small cell lung cancer and head and neck cancer. In head and neck cancer, MEDI4736 is being investigated both as monotherapy and in combination with tremelimumab, looking at patients with different PD-L1 expression status who have failed on chemotherapy. A comprehensive development program for MEDI4736 is underway across multiple tumor types, stages of disease, lines of therapy, and in combination with both immuno-oncology compounds as well as small molecules.