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
United States (several centers), Australia, Canada, Denmark, Guatemala, Hungary, Ireland, Israel, Italy, Korea, Malaysia, Puerto Rico, Singapore, Spain, Taiwan, United Kingdom
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.