Durvalumab Granted Breakthrough Therapy Designation for Bladder Cancer

Monoclonal antibody blocks tumor cells’ attempts to evade detection

The FDA has granted breakthrough therapy status to durvalumab (MEDI4736, AstraZeneca) for the treatment of patients with programmed death ligand-1 (PD-L1)–positive inoperable or metastatic urothelial bladder cancer whose tumor has progressed during or after one standard platinum-based regimen.

Durvalumab is an investigational human monoclonal antibody directed against PD-L1, which is expressed by tumors to evade detection by the immune system through binding to programmed death-1 (PD-1) proteins on cytotoxic T lymphocytes. Durvalumab blocks the PD-L1 interaction with PD-1, countering the tumor’s immune-evading tactics. Durvalumab is being developed to boost patients’ immune systems and attack the cancer.

Durvalumab is being investigated as monotherapy or in combination with tremelimumab (Pfizer/AstraZeneca) in patients with non–small-cell lung cancer; head-and-neck, bladder, gastric, pancreatic, and blood cancers; and hepatocellular carcinoma. Durvalumab is also being tested in first-line bladder cancer as monotherapy and in combination with tremelimumab as part of the ongoing phase 3 DANUBE trial.

The FDA’s breakthrough designation was granted on the basis of early clinical data from a phase 1 trial in patients with advanced metastatic urothelial bladder cancer whose tumor had progressed during or after one standard platinum-based regimen.

Urothelial bladder cancers arise from the epithelium of the bladder and are the ninth most common form of cancer worldwide. The Global Burden of Disease Cancer Collaboration has estimated that there were 400,000 incidents of bladder cancer and 173,000 deaths worldwide in 2013. Patients with metastatic bladder cancer have five-year overall survival rates of less than 15%.

Source: AstraZeneca; February 17, 2016.