Purpose We assessed the safety and antitumor activity of avelumab, a fully human 
anti-programmed death-ligand 1 (PD-L1) IgG1 antibody, in patients with 
refractory metastatic urothelial carcinoma. Methods In this phase Ib, 
multicenter, expansion cohort, patients with urothelial carcinoma progressing 
after platinum-based chemotherapy and unselected for PD-L1 expression received 
avelumab 10 mg/kg intravenously every 2 weeks. The primary objectives were 
safety and tolerability. Secondary objectives included confirmed objective 
response rate (Response Evaluation Criteria in Solid Tumors [RECIST] version 
1.1), progression-free survival, overall survival (OS), and PD-L1-associated 
clinical activity. PD-L1 positivity was defined as expression by 
immunohistochemistry on ≥ 5% of tumor cells. Results Forty-four patients were 
treated with avelumab and followed for a median of 16.5 months (interquartile 
range, 15.8 to 16.7 months). The data cutoff was March 19, 2016. The most 
frequent treatment-related adverse events of any grade were fatigue/asthenia 
(31.8%), infusion-related reaction (20.5%), and nausea (11.4%). Grades 3 to 4 
treatment-related adverse events occurred in three patients (6.8%) and included 
asthenia, AST elevation, creatine phosphokinase elevation, and decreased 
appetite. The confirmed objective response rate by independent central review 
was 18.2% (95% CI, 8.2% to 32.7%; five complete responses and three partial 
responses). The median duration of response was not reached (95% CI, 12.1 weeks 
to not estimable), and responses were ongoing in six patients (75.0%), including 
four of five complete responses. Seven of eight responding patients had 
PD-L1-positive tumors. The median progression-free survival was 11.6 weeks (95% 
CI, 6.1 to 17.4 weeks); the median OS was 13.7 months (95% CI, 8.5 months to not 
estimable), with a 12-month OS rate of 54.3% (95% CI, 37.9% to 68.1%). 
Conclusion Avelumab was well tolerated and associated with durable responses and 
prolonged survival in patients with refractory metastatic UC.