Antibody-drug conjugates in genitourinary malignancies: The clinical trial landscape and emerging efficacy benchmarks.

877 Background: Antibody-drug conjugates (ADCs) are increasingly likely to transform the treatment of genitourinary (GU) malignancies. To comprehensively map the strategic direction and evaluate the emerging evidence base, we analysed the global ADC clinical trial landscape in GU malignancies alongside recently published efficacy and safety outcomes. Methods: We performed a systematic search of the ClinicalTrials.gov database (Oct 2025) for all phase II-IV trials involving ADCs in GU cancers (n=151). Results were filtered to isolate a final cohort of ongoing and completed ADC studies. We extracted data on trial design, disease focus, therapeutic setting, ADC target, and sponsor geography. A corresponding systematic literature search was conducted to identify efficacy and safety benchmarks from the associated ADCs. Results: Our analysis identified 104 unique ADC trials in GU cancers. The pipeline is predominantly focused on urothelial carcinoma (UC; 73% of trials, n=76) and prostate cancer (PC; 18%, n=19). A significant strategic shift towards curative-intent therapy is evident in UC, with 37% (28/76) of trials investigating perioperative settings. Combination with immune checkpoint inhibitors is a dominant strategy (36% of UC trials). The most frequently studied ADC targets are Nectin-4 (n=25), HER2 (n=21), and TROP2 (n=17). Published data from pivotal trials have established key efficacy benchmarks: in first-line metastatic UC, ADC-immunotherapy combinations established a new median overall survival of 33.8 months; in the curative-intent muscle-invasive bladder cancer setting, a pathologic complete response rate of 57.1% has been achieved; and in pre-treated metastatic castration-resistant prostate cancer, promising objective response rates of ~41% are emerging for novel, non-prostate-specific membrane antigen targets. This is accompanied by substantial rates of Grade ≥3 treatment-related adverse events, with distinct, payload-dependent toxicity profiles emerging. Conclusions: The ADC clinical trial landscape in GU oncology is characterised by a strategic intensification in urothelial cancer, with a clear trajectory from metastatic to curative-intent settings driven by practice-changing survival data. A diverse and promising pipeline is emerging in prostate cancer against a portfolio of novel targets. The rapid evolution and maturation of this therapeutic class may continue to redefine treatment standards across the spectrum of GU malignancies.