Two supplemental Biologics License Applications (sBLAs) have been accepted for review by the FDA for pembrolizumab, an anti-PD-1 therapy, in patients with locally advanced or metastatic urothelial cancer.
Specifically, the application for first-line use was accepted and granted Priority Review for the treatment of these patients who are ineligible for cisplatin-containing therapy. The application for second-line use also was accepted and granted Priority Review for these patients with disease progression on or after platinum-containing chemotherapy. The PDUFA, or target action, date for both applications is June 14, 2017.
The FDA previously granted Breakthrough Therapy Designation to pembrolizumab for the second-line treatment of patients with locally advanced or metastatic urothelial cancer with disease progression on or after platinum-containing chemotherapy.
The applications, which are seeking approval for pembrolizumab monotherapy at a dose of 200 mg administered by IV every 3 weeks, are based on data from the phase II KEYNOTE-052 trial and the phase III KEYNOTE-045 trial, respectively.
KEYNOTE-052 is an open-label study investigating pembrolizumab as a first-line treatment in patients with locally advanced or metastatic urothelial cancer who are ineligible for cisplatin-containing therapy. KEYNOTE-045 is a randomized study investigating pembrolizumab as a second-line therapy compared to investigator-choice chemotherapy (paclitaxel, docetaxel, vinflunine) in patients with locally advanced or metastatic urothelial cancer that has recurred or progressed on or after platinum-containing chemotherapy. In October 2016, the trial met its co-primary endpoint of overall survival and was stopped early at the recommendation of an independent Data Monitoring Committee.
Pembrolizumab is being evaluated in over 30 tumor types in more than 400 clinical trials, at least half of which combine the drug with other cancer treatments. Pembrolizumab is a humanized monoclonal antibody that works by increasing the ability of the body's immune system to help detect and fight tumor cells. It blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes that may affect both tumor cells and healthy cells. Pembrolizumab is administered as an IV infusion over 30 minutes every 3 weeks for the approved indications.