Background: Avelumab, a human anti‒PD-L1 IgG1 antibody, is approved for the treatment of metastatic urothelial cancer (mUC) progressing after platinum chemotherapy in the US, Canada, and Israel. Here, we report an updated pooled analysis of 2 cohorts of avelumab-treated patients (pts) with mUC from the JAVELIN Solid Tumor study (NCT01772004). Methods: Pts with mUC whose disease had progressed after platinum-based therapy or were cisplatin ineligible received avelumab 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by independent review (RECIST v1.1). Endpoints included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety (NCI CTCAE v4.0). Results: As of April 2018, 249 pts had received avelumab and had been followed for ≥2 years (median 2.7 years). Median treatment duration was 12.0 weeks (IQR, 6.0-32.1), and 12 pts (4.8%) remained on treatment. Confirmed ORR in all evaluable pts (n = 242) was 16.5% (95% CI: 12.1%-21.8%; complete response in 4.1%). Median DOR was 20.5 mo (95% CI: 9.7-not estimable), and the Kaplan-Meier (K-M) estimate of 12-mo DOR was 65.4% (95% CI: 47.0%-78.8%). Median PFS was 1.6 mo (95% CI: 1.4-2.7 mo), median OS was 7.0 mo (95% CI: 5.9-8.5 mo), and the K-M 12-mo and 24-mo OS rates were 35.9% (95% CI: 29.9%-42.0%) and 20.1% (95% CI: 15.2%-25.4%), respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 71.1% of pts (177/249), most commonly infusion-related reactions (24.1%), fatigue (18.1%) and rash (18.1%). Grade ≥3 TRAEs occurred in 11.6% of pts (29/249), most commonly fatigue (1.6%), elevated lipase (1.6%), and pneumonitis (1.2%). Ten pts (4.0%) discontinued avelumab due to a TRAE. There was 1 treatment-related death (pneumonitis). Conclusions: Avelumab showed durable clinical activity and had a manageable safety profile in pts with mUC. A phase 3 trial of avelumab in the maintenance setting after first-line platinum-based therapy for mUC is ongoing. Clinical trial information: NCT01772004