Background: Programmed cell-death ligand 1 (PD-L1) overexpression is a mechanism for immune escape in UC. Rogaratinib, an oral pan-FGFR1-4 inhibitor, showed promising efficacy in a Phase I study in pts with solid tumors, including UC, with FGFR1-3 mRNA overexpression (Schuler et al. Lancet Oncol 2019). This Phase Ib/II study is evaluating rogaratinib in combination with atezolizumab, a PD-L1 inhibitor, in pts with FGFR-positive, locally advanced or metastatic UC (NCT03473756). We report results from the Phase Ib study. Methods: Cisplatin-ineligible pts with untreated metastatic UC were eligible if high FGFR1 or 3 mRNA was detected by RNA in situ hybridization of archival tissue (RNAscope). Pts were treated at a starting dose of rogaratinib 800 mg p.o. BID and atezolizumab 1200 mg i.v. on day 1 (21-day cycle). Primary objectives were safety, tolerability, and determination of the recommended Phase II dose. Results: 27 pts were treated (rogaratinib 800 mg + atezolizumab, n = 11; rogaratinib 600 mg + atezolizumab, n = 16); 85% were male, median age was 72 years (range 47-83), 37% had an ECOG PS of 1, and 96% had negative/low PD-L1 expression. Most common treatment-emergent adverse events (TEAEs) were diarrhea (63%), hyperphosphatemia (44%), and urinary tract infection (37%). Dose interruption/reduction due to AEs occurred in 67%/37% of pts; TEAEs lead to discontinuation in 45.5% (800 mg) and 12.5% (600 mg). Most common grade 3/4 TEAEs were increased lipase without pancreatitis (11%), rash, and increased alanine aminotransferase (7% each). Rogaratinib-related unique TEAEs were hyperphosphatemia (44%) and retinal pigment epithelium detachment (4%). The maximum tolerated dose (MTD) was rogaratinib 600 mg BID based on lower overall frequency of AEs. Of 23 evaluable pts (600 mg, n = 13; 800 mg, n = 10), overall 9 (39%) pts had an objective response (RECIST v1.1); 3 (13%) pts had a complete response (600 mg: 2/13 pts), 6 (26%) pts had a partial response (600 mg: 5/13 pts), and 6 (26%) pts had stable disease (600 mg: 4/13 pts). Conclusions: Rogaratinib with atezolizumab showed promising efficacy and safety in cisplatin-ineligible pts with tumor FGFR1 or 3 mRNA-positive UC, with nearly all pts demonstrating low or negative PD-L1 expression. Pts are being enrolled at the MTD of rogaratinib 600 mg BID plus atezolizumab. Clinical trial information: NCT03473756.