A Phase III, Open-Label, Multicenter, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Versus Observation as Adjuvant Therapy in Patients With PD-L1-Selected, High-Risk Muscle-Invasive Bladder Cancer After Cystectomy

Hoffman-La Roche
Participating centers: 
United States (several centers), Australia, Belarus, Belgium, Canada, Czech Republic, Finland, France, Denmark, Germany, Greece, Israel, Italy, Korea, Netherlands, Poland, Russian Federation, Serbia, Spain, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom
Study Design: 
Phase III, randomized trial comparing adjuvant atezolizumab versus observation in patients with PD-L1 positive muscle invasive bladder cancer (urothelial histology) status post cystectomy. On the study patients may have had no neo-adjuvant chemotherapy or may have had neo-adjuvant chemotherapy and then after cystectomy are pT2-T4a or N+. No prior adjuvant RT or chemotherapy is allowed.
In a recently reported Phase I trial with update at ASCO 2015 Annual Meeting, Powles et al reported 26% overall response rate with MPDL3280A (atezolizumab) in patients with metastatic urothelial cancer. Results are impressive considering that at least 72% of patients failed 2 or more prior regimens. Therefore, PD-L1 inhibition is being evaluated in patients in an earlier stage of disease in this current trial.
Emerging literature demonstrates that immunotherapies are more effective in patients with limited tumor burden. Given the impressive efficacy from the Phase I trial (as high as 43% in patients with strong PD-L1 expression), this trial optimizes atezolizumab therapy for patients with low tumor burden and PD-L1 expression.