Background: GC has a high overall response rate (ORR) but a high relapse rate in pts with untreated mUC. Inhibition of programmed death-ligand 1 (PD-L1) with A can lead to long-term survival, but single-agent ORR is modest. We report the outcomes of GC+A in a cohort pts with mUC. Methods: This study was designed to assess the safety of GC + A in 10 pts with untreated mUC prior to testing GC + A in a neoadjuvant study in pts with muscle-invasive disease. The primary endpoint was safety as assessed by a predefined dose limiting toxicity (DLT) rate during the first cycle in the first 6 pts. Total accrual goal was 10 pts to collect preliminary data on ORR and progression-free survival (PFS). RECIST 1.1 assessments were performed every 9 wks. Pts received 6 cycles of GC + A induction and then A maintenance every 3 wks. Results: No DLTs occurred during the first cycle in the first 6 pts. Grades 3-4 neutropenia and anemia occurred in 6/10 and 7/10 pts, respectively. Three pts required gemcitabine dose reductions for hematologic toxicity and 2 pts had febrile neutropenia. One pt discontinued cisplatin after 2 cycles for grade 3 hearing impairment but completed induction with gemcitabine and A. Only 1 pt discontinued study therapy due to treatment-related adverse events (AEs), including A-related grade 4 encephalopathy and grade 3 polyneuropathy. Three of 10 pts had visceral (liver or bone) metastases. Of the 10 pts, 1 pt is completing induction but meets initial criteria for partial response (PR), 8 pts had confirmed PR, and 1 pt had progressive disease (PD). Of 9 pts with confirmatory scans, the median PFS was 10.6 months (95% CI 6.7, N/A). Of 8 pts with confirmed PR, 5 eventually had PD, 1 has just completed induction, 1 remains without PD at 25 months, and 1 had consolidation surgery with a pathologic complete response and remains disease-free at 21 months. Conclusions: This 10 pt study met its primary safety endpoint. The neoadjuvant study is ongoing (NCT02989584). Although there were a substantial number of grade 3-4 toxicities, therapy was discontinued due to treatment-related AEs in only 1 pt. Immune correlative studies are ongoing. Clinical trial information: NCT02989584