A Study of Pembrolizumab (MK-3475) Versus Paclitaxel, Docetaxel, or Vinflunine for Participants With Advanced Urothelial Cancer (MK-3475-045/KEYNOTE-045)

Merck Sharp & Dohme Corp
Participating centers: 
United States (several centers), Australia, Austria, Belgium, Canada, Chile, Denmark, France, Germany, Hungary, Ireland, Israel, Italy, Japan, Korea, Netherlands, Norway, New Zealand, Peru, Poland, Portugal, Puerto Rico, Romania, Singapore, Spain, Sweden, Taiwan, Turkey, United Kingdom
In a recently reported multi-cohort Phase 1b Trial, pembrolizumab (PD-1 inhibitor) demonstrated ~15% grade 3-5 adverse events and 28% overall response rate in advanced urothelial cancer failing 2 or more systemic therapies. Therefore, pembrolizumab is being evaluated in a previously treated population. Participants with metastatic or locally advanced/unresectable urothelial cancer that has recurred or progressed following platinum-based chemotherapy will be randomly assigned to receive pembrolizumab or investigator’s choice of paclitaxel, docetaxel, or vinflunine. The primary study hypotheses are that pembrolizumab will prolong OS and PFS.
Checkpoint blockade inhibitors (both PD-1 and PD-L1 inhibition) appear to be active in urothelial cancer. In the USA there is no standard second line therapy for patients who have failed first line cisplatin based chemotherapy. In Europe, vinflunine is approved in this setting. For this reason patients will be randomized between pembrolizumab and the investigator’s choice of chemotherapy.