The U.S. Food and Drug Administration (FDA) has accepted the Biologics License Application (BLA) for the investigational agent enfortumab vedotin, also known as ASG-22CE, and granted Priority Review for the treatment of patients with locally advanced or metastatic urothelial cancer who have received a PD-1/L1 inhibitor and who have received a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting. 
Urothelial cancer is the most common type of bladder cancer, diagnosed in 90% of all cases of the disease. In 2018, more than 82,000 people were diagnosed with bladder cancer in the United States Globally, approximately 549,000 people were diagnosed with bladder cancer last year, and there were approximately 200,000 deaths worldwide.
Antibody-drug conjugates or ADCs are a three-component ‘drug system’ which includes a potent cytotoxic anticancer agent linked via a biodegradable linker to an antibody. The antibody binds to specific markers (antigens or receptors) at the surface of the cancer cell.
The whole antibody-drug conjugate is then internalized within the cancer cell. This focused delivery of the cytotoxic agent to the tumor cell is designed to maximize the anti-tumor effect of the agent while minimizing its normal tissue exposure, potentially leading to an improved therapeutic index. Today there are 5 ADCs commercially approved and available for the treatment of patients with various forms of cancer, while more than 100 agents are in differing forms of clinical trials.
The filing for enfortumab vedotin is based on results from the first cohort of patients in the single-arm EV-201 pivotal phase II clinical trial presented as a late-breaking oral presentation at the annual meeting of the American Society of Clinical Oncology (ASCO) held in Chicago, Ill, in early June 2019.
In the this trial, which includes 2 cohorts, 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.
The first cohort includes patients those who have also been treated with a platinum-containing chemotherapy and those who have not received a platinum-containing chemotherapy. This part of the trial enrolled 128 patients at multiple centers internationally. The second cohort includes patients who are ineligible for cisplatin. This part of the trial continues to enroll patients.
Under the Prescription Drug User Fee Act (PDUFA), a law passed by the United States Congress in 1992 which allowed the Food and Drug Administration to collect fees from drug manufacturers to fund the new drug approval process, a target action date of March 15, 2020, the deadline by which the regulatory agency needs review the new drug application.
Enfortumab vedotin is a novel investigational antibody-drug conjugate (ADC) that targets Nectin-4, a protein that is highly expressed in urothelial cancers and other solid tumors, has been identified as a target for antibody-drug conjugates by Astellas.
The trial drug links an anti-Nectin-4 monoclonal antibody attached to a microtubule-disrupting agent called Monomethyl Auristatin E or MMAE. The linker chemistry used in this drug is developed by Seattle Genetics.
The FDA granted enfortumab vedotin Breakthrough Therapy designation in March 2018, for patients with locally advanced or metastatic urothelial cancer whose disease has progressed during or following checkpoint inhibitor therapy.
“The FDA’s filing of the application for enfortumab vedotin and granting of Priority Review is a significant milestone toward offering a new treatment to patients with advanced urothelial cancer who have a clear unmet need,” noted Roger Dansey, MD., Chief Medical Officer at Seattle Genetics.
“If approved, enfortumab vedotin will likely play an important role in the treatment of advanced urothelial cancer, and we look forward to working with the FDA as the review process advances,” said Andrew Krivoshik, M.D., PhD., Senior Vice President and Oncology Therapeutic Area Head at Astellas.
Astellas and Seattle Genetics are co-developing enfortumab vedotin under a collaboration that was entered into in 2007 and expanded in 2009. Under the collaboration, the companies are sharing costs and profits on a 50:50 basis worldwide.
A Study of Escalating Doses of ASG-22CE Given as Monotherapy in Subjects With Metastatic Urothelial Cancer and Other Malignant Solid Tumors That Express Nectin-4 – NCT02091999
A Study of Enfortumab Vedotin for Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer (EV-201) – NCT03219333
 A Study of Escalating Doses of ASG-22CE Given as Monotherapy in Subjects With Metastatic Urothelial Cancer and Other Malignant Solid Tumors That Express Nectin-4. Online. Bladder Cancer (BCAN). Last accessed September 15, 2019
 American Society of Clinical Oncology. Bladder Cancer: Statistics (05-2019). Online
 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.