Background: Anti-PD-L1 immunotherapy shows promising clinical activity in UC. We report a planned update of the safety and efficacy of durvalumab in patients (pts) with locally advanced/metastatic UC from a multicenter, phase 1/2 open-label study. Methods: Pts received durvalumab 10 mg/kg every 2 weeks (Q2W) up to 12 months (mo) or until unacceptable toxicity, progression, or starting another anticancer therapy. Primary endpoints were safety and confirmed objective response rate (ORR) by blinded independent central review (RECIST v1.1). Duration of response (DoR), progression-free survival (PFS) and overall survival (OS) were key secondary endpoints. Tumor PD-L1 expression was assessed by Ventana SP263 assay (PD-L1 high = ≥25% PD-L1 expression on tumor or immune cells). Results: As of Oct 24, 2016 (data cutoff [DCO]), 191 pts had received treatment. Median follow-up was 5.78 mo (range, 0.4–25.9). All pts had Stage 4 disease and 99.5% had prior anticancer therapy (95.3% post-platinum). As of DCO, ORR was 17.8% (34/191), including 7 CRs, with responses observed regardless of PD-L1 status (Table). Responses occurred early (median time to response, 1.41 mo) and were durable (median DoR not reached [NR]). Median PFS and OS were 1.5 mo (95% CI, 1.4, 1.9) and 18.2 mo (95% CI, 8.1, not estimable [NE]), respectively; the 1-year OS rate was 55.0% (95% CI, 43.9%, 64.7%). Grade 3/4 treatment-related AEs occurred in 6.8% of pts; grade 3/4 immune-mediated (im)AEs occurred in 4 pts; 2 pts discontinued due to imAEs (acute kidney injury and autoimmune hepatitis). Conclusions: Durvalumab 10 mg/kg Q2W shows favorable clinical activity and an excellent safety profile in locally advanced/metastatic UC pts. Table. Antitumor activity in UC pts, including second-line or greater (≥2L) post-platinum pts Clinical trial information: NCT01693562