The study evaluated the efficacy and safety of sacituzumab govitecan (SG) in combination with pembrolizumab for patients with metastatic urothelial cancer (mUC) who progressed after platinum-based chemotherapy. The primary objective was to assess the objective response rate (ORR). Of the 41 patients treated, the central review confirmed an ORR of 41%, meeting the primary endpoint. The combination was generally well tolerated, with no new safety signals observed. The median duration of response (DOR) was 11.1 months, and the median overall survival (OS) was 12.7 months. The study demonstrated encouraging antitumor activity and a manageable toxicity profile, supporting further evaluation of this combination in mUC. The results were compared favorably to historical data from other clinical trials, including KEYNOTE-045, CheckMate 275, and JAVELIN 100 Bladder Solid Tumor studies. The study also highlighted the importance of timely initiation of second-line immunotherapy and the relevance of metastasis site in treatment decisions. Limitations included the single-arm, nonrandomized design and moderate sample size, which could introduce selection and confounding biases. Additional TROPHY-U-01 cohorts are ongoing to further evaluate SG in various settings.The study evaluated the efficacy and safety of sacituzumab govitecan (SG) in combination with pembrolizumab for patients with metastatic urothelial cancer (mUC) who progressed after platinum-based chemotherapy. The primary objective was to assess the objective response rate (ORR). Of the 41 patients treated, the central review confirmed an ORR of 41%, meeting the primary endpoint. The combination was generally well tolerated, with no new safety signals observed. The median duration of response (DOR) was 11.1 months, and the median overall survival (OS) was 12.7 months. The study demonstrated encouraging antitumor activity and a manageable toxicity profile, supporting further evaluation of this combination in mUC. The results were compared favorably to historical data from other clinical trials, including KEYNOTE-045, CheckMate 275, and JAVELIN 100 Bladder Solid Tumor studies. The study also highlighted the importance of timely initiation of second-line immunotherapy and the relevance of metastasis site in treatment decisions. Limitations included the single-arm, nonrandomized design and moderate sample size, which could introduce selection and confounding biases. Additional TROPHY-U-01 cohorts are ongoing to further evaluate SG in various settings.