FDA Grants Breakthrough Therapy Designation to Padcev (enfortumab vedotin) plus Pembrolizumab for First-Line Treatment of Advanced Bladder Cancer

On the 20th, Seagen and Astellas jointly announced that the U.S. FDA has granted Breakthrough Therapy Designation to the combination therapy of their antibody-drug conjugate Padcev (enfortumab vedotin-ejfv) and pembrolizumab, as a first-line treatment for previously untreated patients with locally advanced or metastatic urothelial cancer.

According to the statistics in the press release, approximately 549,000 patients worldwide were diagnosed with urothelial carcinoma in 2018, and about 200,000 patients died from the disease. Urothelial carcinoma accounts for more than 90% of bladder cancer cases. Currently, chemotherapy and PD-1/PD-L1 inhibitors are the standard treatments for patients with bladder cancer. However, treatment options remain very limited for patients who develop resistance to PD-1/PD-L1 inhibitors.

Padcev is an antibody-drug conjugate (ADC) that links an anti-Nectin-4 monoclonal antibody to the microtubule-disrupting agent MMAE. It utilizes Seagen’s proprietary antibody-drug conjugation technology. Nectin-4 is a cell adhesion molecule expressed on the surface of various solid tumors and is highly expressed in urothelial carcinoma. The therapy previously received Breakthrough Therapy Designation and Priority Review from the FDA, and was approved last December as a second-line treatment for patients with locally advanced or metastatic urothelial carcinoma.

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

The granting of this breakthrough therapy designation was based on positive data obtained from its Phase 1b/2 clinical study, named EV-103. In this trial, Padcev in combination with pembrolizumab was evaluated in patients with locally advanced or metastatic urothelial carcinoma who were ineligible for first-line cisplatin-based chemotherapy. The results showed that, with a median follow-up time of 11.5 months, the combination therapy achieved an overall response rate (ORR) of 73%. Among these responses, the complete response (CR) rate was 15.6%, and the partial response rate was 57.8%. Responses were ongoing in 55% of patients, with 83.9% of responders maintaining their response for at least 6 months and 53.7% for at least 12 months. The median progression-free survival (PFS) was 12.3 months, and the 12-month overall survival (OS) rate was 81.6%.

“This Breakthrough Therapy Designation for the combination of Padcev and pembrolizumab as first-line treatment in patients with advanced urothelial cancer who are ineligible for cisplatin-based chemotherapy represents a significant milestone,” said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. “Based on these positive clinical data, we have recently initiated a Phase 3 clinical trial and look forward to addressing unmet medical needs for patients.”

References:

[1] Seattle Genetics and Astellas Receive FDA Breakthrough Therapy Designation for PADCEV™ (enfortumab vedotin-ejfv) in Combination with Pembrolizumab in First-Line Advanced Bladder Cancer, Retrieved February 19, 2020, from https://www.businesswire.com/news/home/20200219005512/en

Note: This article aims to introduce the research progress in medicine and health, and is not a recommendation for treatment plans. If you need guidance on treatment plans, please visit a regular hospital for consultation.

Original Title: Express | First-line Treatment for Advanced Bladder Cancer, ADC Combination Therapy Receives Breakthrough Therapy Designation

▽Follow [WuXi AppTecDe】WeChat Official Account