What You Need to Know About the FDA's Approval of Padcev to Treat Bladder Cancer

The Food and Drug Administration (FDA) approved the first drug to treat adult patients with locally advanced or metastatic urothelial cancer who have received prior treatment with a PD-1/PD-L1 inhibitor and platinum-containing chemotherapy.

The agency granted accelerated approval to the application for Padcev (enfortumab vedotin-ejfv) for this patient population, who had no standard of care prior.

“Typically, for this patient population, there really wasn't anything that was active (in treating patients), and what we’ve seen is about 12% of patients have a complete tumor disappearance. Overall, about 40% of patients have what’s called a partial response and 84% of patients have some form of tumor reduction,” explained Dr. Daniel Petrylak, professor of medicine, medical oncology and urology, and co-leader of Cancer Signaling Networks, at Yale Cancer Center. “So this is really a remarkable finding. To my knowledge, this is the most active single agent (in treating advanced bladder cancer). It is even more active than drugs they've been using in the earlier setting.”

The agency based its decision on data from the multicenter, single-arm, phase 2 pivotal EV-201 trial — designed to evaluate Padcev, which is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer, in 125 patients with locally advanced or metastatic urothelial cancer who received prior treatment with a PD-1 or PD-L1 inhibitor and a platinum-based chemotherapy.

The first-in-class antibody-drug conjugate is approved under the FDA’s Accelerated Approval Program, which allows approval of a medicine based on a surrogate endpoint if the medicine fills an unmet medical need for a serious condition. In this instance, the accelerated approval was based on tumor response rate, the study’s primary endpoint.

“We had a certain goal that we had to meet, which was 30%, and we exceeded that,” Petrylak said. Patients demonstrated an objective response rate of 44%, including 15 complete responses (12%) and 40 partial responses (32%).

Moreover, duration of response, a secondary endpoint of the study, was 7.6 months.

The most common serious side effects were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%) and rash (3%). Peripheral neuropathy led to treatment discontinuation in 6% of patients. Common side effects of any grade included fatigue (56%), peripheral neuropathy (56%), decreased appetite (52%), rash (52%), alopecia (50%), nausea (45%), dysgeusia (42%), diarrhea (42%), dry eye (40%), pruritus (26%) and dry skin (26%).

Continued approval of Padcev will be contingent upon further evaluation to verify and describe the clinical benefit of the drug in a confirmatory trial.

“There are a lot of next steps. This is an exciting drug, and it has a tremendous amount of activity,” Petrylak said. “We’re looking to move this up earlier, in the course of disease. There's a trial being done in patients who've had frontline chemotherapy, and we're looking to (add Padcev) in the neoadjuvant setting prior to somebody having their bladder taken out. And so the thought is that perhaps we'll have more activity earlier.”

Petrylak added that researchers are also looking to add the agent to other combinations, like checkpoint inhibitors.

Read CURE’s original coverage of the approval.