A Phase II Clinical Trial of Pembrolizumab (MK-3475) in Subjects With Advanced/Unresectable or Metastatic Urothelial Cancer (MK- 3475-052/KEYNOTE-52)

Merck Sharp & Dohme Corp
Participating centers: 
United States (several centers), Australia, Canada, Denmark, Guatemala, Hungary, Ireland, Israel, Italy, Korea, Malaysia, Puerto Rico, Singapore, Spain, Taiwan, United Kingdom
Study Design: 
Phase II, single arm interventional trial using pembrolizumab in cisplatin-ineligible, chemotherapy- naïve patients with inoperable and/or metastatic urothelial cancer
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 untreated population (except neoadjuvant chemotherapy >12 months prior) with aggressive disease.
At least two trials now demonstrate the safety and efficacy of checkpoint blockade inhibitors (both PD-1 and PD-L1 inhibition) in urothelial cancer. This new trial will evaluate the impact of PD-1 inhibition in patients with aggressive urothelial cancer who have not been pre-treated. A possible concern with this trial is that PD-1 expression in tumors and tumor infiltrating immune cells may be limited as PD-1 expression increases in response to IFN-γ which can be released from prior treatments. In the absence of prior treatments, up regulation of PD-1 may not be as robust.