Enfortumab vedotin is an investigational antibody-drug conjugate (ADC) that targets Nectin-4, a therapeutic target that is highly expressed in multiple solid tumors including urothelial cancers. Based on preliminary results from a phase 1 trial (EV-101), enfortumab vedotin was granted Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA) for patients with locally advanced or metastatic urothelial cancer whose disease has progressed during or following treatment with a PD-1 or PD-L1 inhibitor.
The companies plan to submit a Biologics License Application (BLA) to the FDA later this year based on the results from the EV-201 trial (cohort 1). A global, randomized phase 3 clinical trial (EV-301) is ongoing and intended to support global registration as well as to serve as the confirmatory randomized trial for enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor.
“Despite recent approvals of multiple checkpoint inhibitors for previously treated locally advanced or metastatic urothelial cancer, there remains a high unmet need for effective treatments upon progression after initial chemotherapy and immunotherapy,” said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. “These results for enfortumab vedotin indicate it may be able to help patients whose urothelial cancer progresses following treatment with standard chemotherapy and a PD-1 or PD-L1 inhibitor.”“After progression on platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor, patients with locally advanced or metastatic urothelial cancer are left with no approved standard of care treatment options,” said Steven Benner, M.D., Senior Vice President and Global Therapeutic Area Head, Oncology Development at Astellas. “These data are very encouraging, and we look forward to discussing the data with relevant health authorities.”
Urothelial cancer is the most common type of bladder cancer (90 percent of cases).1 In 2018, more than 82,000 people were diagnosed with bladder cancer in the United States.2 Globally, approximately 549,000 people were diagnosed with bladder cancer last year, and there were approximately 200,000 deaths worldwide.3 Approximately 80 percent of people do not respond to PD-1 or PD-L1 inhibitors after a platinum-containing therapy has failed as an initial treatment for advanced disease.4 There are currently no approved therapies for metastatic urothelial cancer once it has progressed after chemotherapy and a PD-1 or PD-L1 inhibitor.5
In addition to the ongoing confirmatory phase 3 study intended to also support global registration, development of enfortumab vedotin is underway in earlier lines of treatment for locally advanced or metastatic urothelial cancer, including in newly diagnosed patients in combination with pembrolizumab and/or platinum chemotherapy.
About The EV-201 Trial
EV-201 is an ongoing single-arm, pivotal phase 2 clinical trial of enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1 or PD-L1 inhibitor, including those who have also been treated with a platinum-containing chemotherapy (cohort 1) and those who have not received a platinum-containing chemotherapy and who are ineligible for cisplatin (cohort 2). The EV-201 phase 2 trial continues to enroll patients in cohort 2. In cohort 1, 128 patients were enrolled at multiple centers internationally.6 The primary endpoint is confirmed objective response rate per blinded independent central review. Secondary endpoints include assessments of duration of response, disease control rate, progression-free survival, overall survival, safety, and tolerability. More information about enfortumab vedotin clinical trial.
Seattle Genetics Conference Call Details
Seattle Genetics’ management will host a conference call and webcast to discuss the announcement of enfortumab vedotin topline data. The event will be held today at 6:00 a.m. Pacific Time (PT); 9:00 a.m. Eastern Time (ET). The live event will be available from the Seattle Genetics website, under the Investors section, or by calling 866-288-0540 (domestic) or 786-460-7199 (international). The conference ID is 3807860. A replay of the live event will be available starting on March 28, 2019 on the Seattle Genetics website or by calling 888-203-1112 (domestic) or 719-457-0820 (international), using conference ID 3807860. The telephone replay will be available until 5:00 p.m. PT on April 1, 2019.
Information about pharmaceutical products (including products currently in development), which is included in this press release is not intended to constitute an advertisement or medical advice.
- Companies Plan to Submit Biologics License Application Later This Year -
References:
1. American Society of Clinical Oncology. Bladder Cancer: Introduction (10-2017).
2. https://gco.iarc.fr/today/data/factsheets/populations/840-united-states-of-america-fact-sheets.pdf
3. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424.
4. Alhalabi O, Shah AY, Lemke EA, Gao J (2019). Immune checkpoint inhibitors in urothelial cancer. Oncology (Williston Park) 33(1): 1108.
5. National Comprehensive Cancer Network. Bladder Cancer (Version 1.2019).
6. Data on file at Seattle Genetics