Astellas, Seagen Announce PADCEV Trial Results for Urothelial Cancer

Astellas Pharma and Seagen announced primary results from the phase 3 EV-301 trial comparing PADCEV® (enfortumab vedotin-ejfv) to chemotherapy in adult patients with locally advanced or metastatic urothelial cancer who were previously treated with platinum-based chemotherapy and a PD-1/L1 inhibitor. At the time of pre-specified interim analysis, patients who received PADCEV in the trial lived a median of 3.9 months longer than those who received chemotherapy. Median overall survival was 12.9 vs. 9.0 months, respectively (HR=0.70 [95 percent Confidence Interval (CI): 0.56-0.89], p=0.001). For patients in the PADCEV arm of the trial, maculopapular rash, fatigue and decreased neutrophil count were the most frequent Grade 3 or greater treatment-related adverse events (TRAEs) occurring in more than 5 percent of patients.

Urothelial cancer is the most common type of bladder cancer and can also be found in the renal pelvis, ureter and urethra.

"Improving survival is especially meaningful in patients who have had their cancer progress following chemotherapy or other treatment," said Daniel P. Petrylak, M.D., Professor of Medicine and of Urology, Yale Cancer Center, and corresponding author of the published study.

"Enfortumab vedotin is the first medicine to reduce the risk of death compared to chemotherapy in patients with locally advanced or metastatic urothelial cancer who have received a platinum-containing chemotherapy and an immunotherapy," said Professor Thomas Powles, M.D., Director, Barts Cancer Centre, Queen Mary University of London, who presented results at ASCO GU.

Urothelial cancer is the most common type of bladder cancer (90 percent of cases) and can also be found in the renal pelvis (where urine collects inside the kidney), ureter (tube that connects the kidneys to the bladder) and urethra. Globally, approximately 549,000 new cases of bladder cancer and 200,000 deaths are reported annually.

The EV-301 trial (NCT03474107) is a global, multicenter, open-label, randomized phase 3 trial designed to evaluate enfortumab vedotin versus physician's choice of chemotherapy (docetaxel, paclitaxel or vinflunine) in approximately 600 patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1/L1 inhibitor and platinum-based therapies. The primary endpoint is overall survival and secondary endpoints include progression-free survival, overall response rate, duration of response and disease control rate, as well as assessment of safety/tolerability and quality-of-life parameters.

PADCEV was approved by the U.S. Food and Drug Administration (FDA) in December 2019 and is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic setting. PADCEV was approved under the FDA's Accelerated Approval Program based on tumor response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

PADCEV is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer. Nonclinical data suggest the anticancer activity of PADCEV is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).4 PADCEV is co-developed by Astellas and Seagen.