WASHINGTON -- The enfortumab vedotin-ejfv (Padcev) on Wednesday for treating patients with locally advanced or metastatic urothelial cancer whose disease has progressed on chemotherapy and immunotherapy.
"Padcev is an antibody-drug conjugate that targets Nectin-4, a cell surface protein expressed on bladder cancer cells and a cell-killing agent, monomethyl auristatin E," explained Richard Pazdur, MD, the FDA's top hematology/oncology official, in a statement.
Accelerated approval of the agent was based on findings from the single-arm phase II EV-201 trial, which tested enfortumab vedotin in patients that had failed on both platinum-based chemotherapy and a PD-1/PD-L1 checkpoint inhibitor, a host of which are approved for the disease.
Among the 125 patients on study, 44% responded to the drug, including 12% that achieved a complete response. Median duration of response was 7.6 months.
Overall survival data, presented earlier this year at the American Society of Clinical Oncology annual meeting, demonstrated that patients lived a median 11.7 months following treatment with enfortumab vedotin.
"This is very exciting progress as we haven't had another therapy option for patients whose urothelial or bladder cancer has progressed after chemotherapy or immunotherapy," study investigator Daniel Petrylak, MD, of Yale Cancer Center in New Haven, Connecticut, said in a announcing the approval. "To my knowledge, this is the most active single drug in urothelial cancer."
Enfortumab vedotin was administered intravenously at a dose of 1.25 mg/kg on days 1, 8, and 15 of 28-day cycles. Of note, 36% of patients with liver metastases responded to the drug, a disease site where chemotherapy and immunotherapy have both shown limited effectiveness.
Common adverse events in EV-201 included fatigue, altered taste, dry eye, peripheral neuropathy, a number of gastrointestinal toxicities (decreased appetite, nausea, diarrhea), and various skin-related events (rash, alopecia, pruritus, dry skin).
FDA warned of the risk for hyperglycemia even in patients with no history of diabetes and recommended dose reductions, treatment breaks, or discontinuation for new-onset or worsening peripheral neuropathy. Infusion extravasation may lead to delayed site reactions, they noted.
Under conditions for the accelerated approval of enfortumab vedotin, drugmaker Astellas Pharma must conduct a confirmatory trial to verify the drug's clinical benefit.