LBA55Initial results from TROPHY-U-01: A phase II open-label study of sacituzumab govitecan in patients (Pts) with metastatic urothelial cancer (mUC) after failure of platinum-based regimens (PLT) or immunotherapy

Summary: Patients with metastatic urothelial carcinoma who have progressed on platinum-based combination chemotherapy and checkpoint inhibitors have limited treatment options with low objective response rates. Sacituzumab govitecan, a TROP-2-targeted antibody-drug conjugate, has shown promising activity in this patient population, with notable efficacy compared to historical controls.

Summary: Urothelial carcinoma is a common genitourinary malignancy with poor prognosis. Sacituzumab govitecan, an ADC targeting Trop-2, has shown promising efficacy and safety in the treatment of locally advanced and metastatic urothelial cancer. However, not all patients respond to this therapy, highlighting the importance of understanding resistance mechanisms and predictive biomarkers for improved outcomes.

Summary: In this study, we investigated the expression levels of the drug target TROP2 across different molecular subtypes of bladder cancer in multiple patient cohorts and cell lines. We found high levels of TROP2 in most subtypes except in the neuroendocrine subtype. Overall, TROP2 gene expression is higher than NECTIN4 gene expression, and cells resistant to enfortumab vedotin (EV), a NECTIN4-targeting antibody-drug conjugate, remain sensitive to sacituzumab govitecan (SG). Our findings suggest that SG may be effective across most bladder cancer subtypes, including the bladder cancers previously treated with EV.

Summary: This review discusses the available data on Sacituzumab govitecan for the treatment of locally advanced or metastatic urothelial cancer, including its mechanism of action, pharmacology, efficacy, and safety.

Summary: Results from JAVELIN Bladder 100 established avelumab as the standard-of-care treatment for advanced urothelial carcinoma. The ongoing JAVELIN Bladder Medley trial aims to evaluate the efficacy and safety of avelumab in combination with other anticancer drugs for maintenance therapy. This trial will provide valuable insights into improving the benefit of avelumab maintenance treatment.