Enfortumab Vedotin Granted Breakthrough Designation for Metastatic Bladder Cancer

The US Food and Drug Administration (FDA) has granted a Breakthrough Therapy designation to an antibody-drug conjugate known as enfortumab vedotin. The designation is specifically for patients with locally advanced or metastatic urothelial cancer who have previously been treated with immune checkpoint inhibitors.

“The FDA Breakthrough Therapy designation underscores the potential of enfortumab vedotin as a meaningful treatment for patients with locally advanced or metastatic urothelial cancer,” said Robert Lechleider, MD, the vice president of clinical development at Seattle Genetics, according to a press release. The company is developing the therapy along with Astellas.

The antibody-drug conjugate consists of an anti–nectin-4 monoclonal antibody, combined with the microtubule-disrupting agent MMAE. Nectin-4 is a cell adhesion molecule that is expressed on a number of solid tumor cells. The Breakthrough Therapy designation was granted based on interim results of a phase I trial, which the companies developing the agent have not yet released. Breakthrough Therapies are those that are intended to treat a serious or life-threatening disease or condition, and that have preliminary clinical evidence indicating a substantial improvement over existing therapies.

In recent years, a number of new agents have been approved for treatment of urothelial carcinoma. In 2017, three new immunotherapy agents were approved-pembrolizumab, avelumab, and durvalumab-the latter two specifically in locally advanced or metastatic disease. A total of five checkpoint inhibitors are now approved in this malignancy.

In general, not all patients respond to checkpoint inhibition, suggesting the need for other approaches, such as that pursued with enfortumab vedotin. “Achieving Breakthrough Therapy designation for enfortumab vedotin is another step forward in our goal to bring an additional option to patients who need it most,” said Steven Benner, MD, the senior vice president of oncology development at Astellas. The companies have launched a phase II trial of the antibody-drug conjugate, and are also testing it in other solid tumors, including ovarian and non–small-cell lung cancers.