Immunotherapy uses substances to stimulate or suppress the immune system to help the body fight cancer, infection, and other diseases. One kind of immunotherapy uses monoclonal antibodies— drugs designed to bind to specific targets in the body that can cause an immune response that destroys cancer cells.

The National Cancer Institute (NCI) played an instrumental role in developing and expediting the FDA’s approval of EMD Serono’s checkpoint inhibitor avelumab (Bavencio®) through NCI’s Cooperative Research and Development Agreement (CRADA) with EMD Serono. EMD Serono is the biopharmaceutical business of Merck KGaA, Darmstadt, Germany, in the U.S. and Canada. Avelumab is a human monoclonal antibody that targets the PD-L1 checkpoint protein. Through this CRADA, NCI performed early preclinical studies of avelumab that evaluated its efficacy and produced promising results, and NCI published data showing avelumab’s ability to mediate antibody-dependent, cell-mediated cytotoxicity (ADCC). NCI conducted several critical studies that led to FDA approval.

Once these studies were performed, the clinical trial was open to multiple patient groups. To date, over 1700 patients have been enrolled in this study and received treatment with investigational avelumab. Results from the study directly led to the FDA’s accelerated approval of avelumab for the treatment of previously treated, locally advanced or metastatic urothelial carcinoma. This accelerated approval was the second approval of avelumab within two months.

Bladder cancer makes up approximately 90% of urothelial carcinomas, and is the sixth most common cancer in the U.S. When the disease has metastasized, the 5-year survival rate is approximately 5%. Avelumab’s accelerated approval provides patients with an important treatment option that will hopefully improve outcomes for these patients. Also, the safety data of the study supported the FDA’s accelerated approval of avelumab for the treatment of metastatic Merkel cell carcinoma (MCC), a rare and aggressive skin cancer with fewer than half of patients surviving more than one year and fewer than 20% surviving beyond 5 years, representing a significant unmet need. NCI participated in a phase II MCC study conducted at multiple centers, including NCI. Avelumab is now the first FDAapproved drug for the treatment of metastatic MCC. Currently, multiple clinical studies of avelumab are being conducted for other types of cancer under this CRADA.

Winners:

Andrea Apolo

Isaac Brownell

James Gulley, M.D.

Jeffrey Schlom, Ph.D.

John Greiner, Ph.D.

Julius Strauss

Kevin Brand

Ravi Madan, M.D.

Renee Donahue, Ph.D.

Michael Pollack

Contact: Dr. James Gulley, (301) 480-8870, [email protected]