enfortumab vedotin向FDA申请扩大局部晚期或转移性尿路上皮癌的适应症

On February 18, 2021, two supplemental biologics license applications for Padcev (enfortumab vedotin-ejfv) have been submitted to the FDA to convert the drug's accelerated approval to regular approval and expand the current indication to include patients with locally advanced or metastatic urothelial cancer who have received prior PD-1/PD-L1 inhibitor therapy and are not suitable for cisplatin treatment.

The first application is based on data from the Phase 3 EV-301 trial (NCT033474107), in which Padcev demonstrated efficacy and survival advantages over chemotherapy in this patient population. Median overall survival (OS) was 12.88 months (95% CI, 10.58-15.21) with Padcev compared with 8.97 months (95% CI, 8.05-10.74) with chemotherapy (HR, 0.70; 95% CI, 0.56-0.89; P = .00142).

The second application is based on results from the second cohort of the phase 2 EV-201 trial (NCT032193333), in which Padcev achieved the highest response rate of all regimens in patients with locally advanced or metastatic urothelial cancer who had previously been treated with a PD-1/PD-L1 inhibitor and were ineligible for cisplatin. The confirmed objective response rate (ORR) achieved with Padcev was 52% (95% CI, 40.8%-62.4%).

"The FDA's review of our application based on real-time oncology supports us in expanding the indications for [enfortumab vedotin] as quickly as possible to provide treatment options to more patients. Locally advanced or metastatic urothelial cancer is an aggressive disease with limited treatment options," Andrew Krivoshik, MD, senior vice president and head of oncology therapeutics at Astellas, said in a press release.

In December 2019, the FDA granted accelerated approval to enfortumab vedotin for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received PD-1/PD-L1 inhibitors and platinum-containing chemotherapy. The decision was based on data from the first cohort of EV-201, in which Padcev resulted in an ORR of 44%; this included a complete response (CR) rate of 12% and a partial response rate of 32%.

Urothelial cancer most commonly occurs in the bladder (90%). According to the American Cancer Society, approximately 79,000 people in the United States will be diagnosed with bladder cancer in 2017, and nearly 17,000 will die from the disease. Patients diagnosed with metastatic disease have a poor prognosis, with a 5-year survival rate of 5%.

Enfortumab vedotin-ejfv is an antibody-drug conjugate. Enfortumab vedotin uses Seattle Genetics' proprietary linkage technology to link the microtubule-disrupting agent MMAE and an anti-nectin-4 monoclonal antibody. Enfortumab vedotin targets the cell adhesion molecule nectin-4 expressed on a variety of solid tumors.

Reference: FDA Approval Sought for Enfortumab Vedotin in Locally Advanced or Metastatic Urothelial Cancer