Maillet, Denis

4562 Background: Approximately 50-80% of patients (pts) with la/mUC have tumors with HER2 protein expression. As HER2-directed therapies enter development, a robust understanding of HER2 prevalence and real-world outcomes with standard-of-care (SOC) therapies across HER2 expression subgroups is needed. SGNDV-003 (NCT05902494) is a global retrospective chart review study in which HER2 status was assessed via central lab testing and outcomes were analyzed by HER2 status in pts with la/mUC. Methods: SGNDV-003, conducted 6/2023-7/2025, included pts with la/mUC who received ≥1 prior treatment (tx) (incl. 1 line of platinum-based chemotherapy [chemo]). HER2 status was centrally tested using a UC-specific investigational immunohistochemistry [IHC] and in situ hybridization (ISH) assays. HER2 status was defined as: HER2-positive (IHC3+ or IHC2+/ISH+), HER2-low (IHC2+/ISH- or IHC1+), HER2-expressing (IHC3+, 2+, 1+), and HER2-zero (IHC0). Index line of therapy (LOT) was defined as the first LOT received after platinum-based chemo. Outcomes included real-world objective response rate (rwORR) (per RECIST 1.1 or physician-assessed response) to index LOT, real-world progression-free survival (rwPFS), and overall survival (OS) from start of index LOT. Data was analyzed via descriptive statistics. Results: A total of 353 pts with la/mUC and available HER2 status were analyzed (male, 76%; median age, 70 years). 70% of pts were HER2 expressing (19% HER2-positive, 51% HER2-low); 30% were HER2-zero. Disease characteristics were well balanced by HER2 status. Index LOT tx and real-world outcomes are shown in the Table. Immuno-oncology therapies (IO) and enfortumab vedotin (EV) were the most common index LOTs. For IO, rwORRs were 21% for HER2-expressing and 17% for HER2-zero. For EV mono, rwORRs were 36% (HER2-expressing) and 38% (HER2-zero), respectively. Conclusions: This global study provides a robust estimate of HER2 distribution in la/mUC based on standardized central lab testing, showing high prevalence of HER2 expression. Real-world outcomes with current SOC therapies were broadly consistent across HER2 subgroups, establishing an important benchmark for the clinical development of HER2-directed therapies in this setting. HER2-positive (n=67) HER2-low (n=181) HER2-expressing (n=248) HER2-zero (n=105) Total (n=353) Real-world Outcomes rwORR, n (%)[95% CI] 17 (25.4)[15.5, 37.5] 50 (27.6)[21.3, 34.7] 67 (27.0)[21.6, 33.0] 22 (21.0)[13.6, 30.0] 89 (25.2)[20.8, 30.1] Median rwPFS (95% CI), mo 2.8(2.0, 4.1) 3.7(2.7, 5.1) 3.0(2.7, 4.5) 2.6(2.1, 3.4) 2.9 (2.6, 3.5) Median OS(95% CI), mo 12.2(9.3, 16.5) 11.5(9.5, 13.5) 11.9(10.3, 13.4) 7.7(5.9, 9.9) 10.8(9.1, 12.3) Index LOT, n% IO EV monoChemoOther tx 37 (55)17 (25)10 (15)3 (5) 94 (52)51 (28)24 (13)14 (8) 131 (53)68 (27)34 (14)17 (7) 65 (62)21 (20)12 (11)7 (7) 196 (56)89 (25)46 (13)24 (7)