Seattle Genetics and Astellas announced that the U.S. FDA has granted Breakthrough Therapy designation for Padcev (enfortumab vedotin-ejfv) in combination with Merck’s Keytruda (pembrolizumab) for the treatment of patients with unresectable locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy in the first-line setting.

The FDA’s Breakthrough Therapy process is designed to expedite the development and review of drugs that are intended to treat a serious or life-threatening condition. Designation is based upon preliminary clinical evidence indicating that the drug may demonstrate substantial improvement over available therapies on one or more clinically significant endpoints. 

The Breakthrough Therapy designation was granted based on results from the dose-escalation cohort and expansion cohort A of the phase 1b/2 trial EV-103, evaluating patients with locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy treated in the first-line setting with Padcev in combination with pembrolizumab. Initial results from the trial were presented at the European Society of Medical Oncology (ESMO) 2019 Congress, and updated findings at the 2020 Genitourinary Cancers Symposium. The data demonstrated the combination of enfortumab vedotin plus pembrolizumab shrank tumors in the majority of patients, resulting in a confirmed objective response rate (ORR) of 71%. The complete response (CR) rate was 13%. Fifty-eight percent (26/45) of patients had a partial response and 22% (10/45) had stable disease. Ninety-one percent of responses were observed at the first assessment. The study also met outcome measures for safety.

About Padcev (enfortumab vedotin-ejfv)

Enfortumab vedotin is an antibody-drug conjugate (ADC) composed of an anti-Nectin-4 monoclonal antibody attached to a microtubule-disrupting agent, MMAE, using Seattle Genetics’ proprietary linker technology. Enfortumab vedotin targets Nectin-4, a cell adhesion molecule that is expressed on many solid tumors, and that has been identified as an ADC target by Astellas.

About Urothelial Cancer

Urothelial cancer is a cancer that begins in cells called urothelial cells that line the urethra, bladder, ureters, renal pelvis, and some other organs. It is estimated that approximately 81,000 people in the U.S. will be diagnosed with bladder cancer in 2020. Urothelial cancer accounts for 90 percent of all bladder cancers and can also be found in the renal pelvis, ureter and urethra. Globally, approximately 549,000 people were diagnosed with bladder cancer in 2018, and there were approximately 200,000 deaths worldwide. 

The recommended first-line treatment for patients with advanced urothelial cancer is a cisplatin-based chemotherapy. For patients who are unable to receive cisplatin, such as people with kidney impairment, a carboplatin-based regimen is recommended. However, fewer than half of patients respond to carboplatin-based regimens and outcomes are typically poorer compared to cisplatin-based regimens.

Source: Seattle Genetics

Pin It on Pinterest