PADCEV succeeds in confirmatory phase 3 trial in urothelial cancer

Seattle Genetics and Astellas Pharma said that PADCEV (enfortumab vedotin-ejfv) met the primary endpoint of overall survival (OS) in a confirmatory phase 3 trial in previously treated locally advanced or metastatic urothelial cancer.

The global trial called EV-301 compared PADCEV to chemotherapy in nearly 600 patients who had prior treatment with platinum-based chemotherapy and a PD-1/L1 inhibitor.

Co-developed by the two firms, the antibody-drug conjugate (ADC) was granted accelerated approval in late 2019 by the US Food and Drug Administration (FDA) for the same condition.

The approval is for the treatment of adults who were previously treated with a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy before or after surgery or in a locally advanced or metastatic setting.

In the EV-301 clinical trial, PADCEV delivered significant improvement in overall survival (OS), with a reduction of 30% in risk of death.

It also considerably improved progression-free survival (PFS), a secondary endpoint of the late-stage trial, by delivering a 39% reduction in risk of disease progression or death.

Astellas Pharma senior vice president and oncology therapeutic area head Andrew Krivoshik said: “EV-301 is the first randomized trial to show overall survival results compared to chemotherapy in patients with locally advanced or metastatic urothelial cancer who previously have received platinum-based treatment and a PD-1 or PD-L1 inhibitor, and we are encouraged by the potential this may have in helping patients who have otherwise limited alternatives.”

Seattle Genetics and Astellas Pharma said that the EV-301 study expect to support the continued approval by the FDA of the drug in the urothelial cancer indication.

The partners will submit the results of the trial to the US regulator besides using them for supporting global registrations for the drug.

Seattle Genetics chief medical officer Roger Dansey said: “These survival results from the confirmatory trial for PADCEV are welcome news for patients whose cancer has progressed after platinum-based chemotherapy and immunotherapy.

“We continue to explore PADCEV’s activity across the spectrum of urothelial cancer including its potential for use in earlier lines of therapy.”

PADCEV has been developed to target Nectin-4, a protein located on the surface of cells and expressed highly in bladder cancer.