FDA grants accelerated approval to Padcev for the treatment of locally advanced or metastatic urothelial cancer. Seattle Genetics + Astellas

Seattle Genetics, Inc and Astellas Pharma Inc. announced that the FDA granted accelerated approval to Padcev for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1/L1 inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic setting.

Padcev is approved under the FDA�s Accelerated Approval Program based on tumor response rate. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials. Padcev is the first FDA approved treatment in the U.S. for these patients. It is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.

Padcev was evaluated in the pivotal trial EV-201, a single-arm phase II multi-center trial that enrolled 125 patients with locally advanced or metastatic urothelial cancer who received prior treatment with a PD-1 or PD-L1 inhibitor and a platinum-based chemotherapy. In the study, the primary endpoint of confirmed objective response rate (ORR) was 44 percent per blinded independent central review (55/125; 95% Confidence Interval [CI]: 35.1, 53.2). Among patients treated with the single agent Pdcev, 12 percent (15/125) experienced a complete response, meaning no cancer could be detected at the time of assessment, and 32 percent (40/125) experienced a partial response, meaning a decrease in tumor size or extent of cancer in the body. The median duration of response (DoR), a secondary endpoint, was 7.6 months (95% CI: 6.3, not estimable [NE]). The most common serious adverse reactions ( greater than 3%) were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%), and rash (3%). The most common adverse reaction leading to discontinuation was peripheral neuropathy (6%). The most common adverse reactions ( greater than 20%) were fatigue (56%), peripheral neuropathy (56%), decreased appetite (52%), rash (52%), alopecia (50%), nausea (45%), dysgeusia (42%), diarrhea (42%), dry eye (40%), pruritus (26%) and dry skin (26%). The most common Grade greater than 3 adverse reactions (greater than 5%) were rash (13%), diarrhea (6%) and fatigue (6%).