Background: Four-to-six cycles ofplatinum-based CTx have been a standard treatment for aUC. However, disease progresses within several months after completion of 1L CTx. Switch maintenance after 1L with effective and safe regimen is an attractive approach to delay disease progression. PEM showed modest response as a salvage CTx in aUC with mild toxicities, which are good candidate for maintenance therapy. We evaluated PEM as switch maintenance therapy versus OBS in pts with aUC whose disease had not progressed. Methods: Eligible pts with aUC without disease progression after 4-6 cycles of either cisplatin or carboplatin-based regimen were randomized 1:1 to receive maintenance PEM (500 mg/m² IV q3 weeks, up to 16 cycles) or OBS until disease progression, stratified by Galsky et al.’s post-treatment prognostic nomogram for pts with mUC completing 1L cisplatin-based CTx. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival (OS), response rate, and safety. Results: This trial was closed early due to poor accrual after avelumab maintenance approval. From Oct 2016 to Dec 2022, a total of 97 pts was randomly assigned to maintenance PEM (n=49) or OBS (n=48). Median age (range) was 69 years (43-90) and 66 (33-82), and male was 63% and 73%, respectively. 1L regimen included gemcitabine plus cisplatin (84% and 83%, respectively), gemcitabine plus carboplatin (12% and 6%, respectively), and MVAC (4% and 10%, respectively). Response to 1L were CR (8% vs. 19%), PR (69% vs. 67%), and SD (22% vs. 15%). Most common metastatic site was abdominopelvic lymph nodes (61% and 65%) and lung (37% and 29%). For PEM group, median administered cycle was 6 (range 1-16), and most common reason for discontinuation was disease progression (53%), followed by completion of planned cycles (20%). With a median follow-up of 19.1 months, median PFS was 6.0 months (mo) [95% confidence interval (CI) 3.4-8.5] for PEM vs. 2.3 mo (1.8-2.7) with a log rank p=0.027, with a hazard ratio (HR) of 0.61 (95% CI 0.40-0.95). Median OS was 25.5 mo (95% CI 11.9-30.1) vs. 26.8 (11.9-41.7) (p=0.607, HR 1.18, 95% CI 0.62-2.26). Anemia (29%), fatigue (18%), and neutropenia (12%) were the most frequent adverse events, and these adverse events were mostly grade 1 or 2, and manageable. Conclusions: PREMIER trial showed that switch maintenance PEM prolonged PFS with statistical significance in aUC after 1L platinum-based CTx and had very favorable safety profile. Combination maintenance therapy including PEM needs further investigation. Clinical trial information: NCT03193788.