In the multi-institutional study, a novel drug called enfortumab vedotin (EV) produced responses in 44% of patients with locally advanced or metastatic urothelial cancer who had been previously treated with chemotherapy and immune therapy using checkpoint inhibitors, which block proteins that stop the immune system from attacking cancer cells.

There are no approved treatment options for patients with advanced bladder cancer after they’ve received standard chemotherapy and immune treatments, but the results of a phase 2 clinical trial led by Yale Cancer Center and Smilow Cancer Hospital researchers demonstrate an effective treatment for this deadly disease. The findings were presented today at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL.

“We really haven’t had another therapy option for patients with urothelial or bladder cancer, so we’re very excited about these findings,” said study lead author Daniel P. Petrylak, MD, professor of medical oncology and urology and co-director of the Signal Transduction Research Program at Yale Cancer Center.

EV is an antibody-drug conjugate, a type of therapy that combines an antibody that targets a specific protein on the surface of tumor cells with a payload of powerful chemotherapy. “Basically, it’s a smart bomb,” says Petrylak.

EV uses an antibody that targets a protein known as Nectin-4, expressed in high levels on the surface of urothelial tumor cells and low levels on normal cells. This antibody is chemically linked with an agent that penetrates the tumor cell and destroys its structure.

Among 125 patients who had received both standard chemotherapy plus a checkpoint inhibitor and EV, 12% had a complete response with no detectable sign of cancer. Median overall survival was 11.7 months. Notably, 38% of people whose cancer had metastasized to the liver responded to the treatment; the liver is a site which has been resistant to both standard chemotherapy and immune therapy, Petrylak said.

An earlier phase 1 clinical study had shown that EV was safe to administer for this patient population. “Our phase 2 results replicate the phase 1 results very closely,” Petrylak noted.

The researchers now are proceeding with a phase 3 randomized trial that will compare EV against standard chemotherapy for this patient population. A phase 1 trial also is underway to examine the drug’s benefits for people who are newly diagnosed with advanced urothelial cancer but are ineligible for chemotherapy. Additionally, another phase 1 trial is looking at treating advanced or metastatic disease by combining EV with the checkpoint inhibitor pembrolizumab.

Yale researchers collaborated on the trial with scientists from Barbara Ann Karmanos Cancer Institute, Dana-Farber Cancer Institute, Johns Hopkins University School of Medicine, Memorial Sloan Kettering Cancer Center, Perlmutter Cancer Center, Tisch Cancer Institute, University of Chicago Comprehensive Cancer Center, University of Washington at Seattle, Astellas Pharma US, and Seattle Genetics. The trial was supported by Seattle Genetics and Astellas Pharma.