Phase 3 Trial of First-in-Class ADC Padcev (enfortumab vedotin-ejfv) Terminated Early Following 30% Reduction in Bladder Cancer Mortality Risk

Recently, Seagen and Astellas announced that Padcev (enfortumab vedotin-ejfv), an antibody-drug conjugate jointly developed by the two companies, met the primary endpoint of overall survival in a Phase 3 clinical trial involving patients with locally advanced or metastatic urothelial carcinoma who had previously received platinum-based chemotherapy and PD-1/PD-L1 inhibitors. Based on these positive interim analysis results, the clinical trial will be terminated early.

Globally, approximately 580,000 people were diagnosed with bladder cancer in 2020. Urothelial carcinoma accounts for 90% of all bladder cancers and can also occur in the renal pelvis, ureters, and urethra. After failure of initial platinum-based chemotherapy, 80% of patients with advanced disease do not respond to PD-1 or PD-L1 inhibitor therapy.

Padcev is an antibody-drug conjugate that links an anti-nectin-4 monoclonal antibody to a microtubule inhibitor. Nectin-4 is a cell adhesion molecule highly expressed in urothelial carcinoma. Based on response rate data, the therapy received accelerated approval from the U.S. FDA last December for the treatment of patients with locally advanced or metastatic urothelial carcinoma who had previously been treated with platinum-containing chemotherapy and PD-1/PD-L1 inhibitors.

▲Mechanism of Action of Padcev (Image source: Seagen official website)

In this clinical trial, compared with the chemotherapy control group, Padcev significantly improved overall survival in patients, reducing the risk of death by 30% (HR=0.70, 95% CI: 0.56, 0.89, p=0.001). Padcev also significantly improved progression-free survival, reducing the risk of disease progression or death by 39% (HR=0.61, 95% CI: 0.50, 0.75, p<0.00001).

These study results will be submitted to the U.S. FDA as confirmatory trial data to support the conversion of accelerated approval to full approval. They will also support global regulatory submissions.

“The survival outcomes for Padcev observed in the confirmatory trial are good news for patients whose disease continued to progress after platinum-based chemotherapy and immunotherapy,” said Dr. Roger Dansey, Chief Medical Officer of Seagen. “We will continue to explore the potential of Padcev in the treatment of urothelial cancers.”

References:

[1] Seattle Genetics and Astellas Announce PADCEV® (enfortumab vedotin-ejfv) Significantly Improved Overall Survival in Phase 3 Trial in Previously Treated Locally Advanced or Metastatic Urothelial Cancer. Retrieved September 18, 2020, from https://www.businesswire.com/news/home/20200918005101/en

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