TROPHY-U-01, a phase II open-label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors: updated safety and efficacy outcomes

Antibody–drug conjugates in cancer therapy: mechanisms and clinical studies

“… 137 , 138 , 139 The efficacy of SG was observed across various malignancies, with promising results seen in histological cohorts of NSCLC, small cell lung cancer (SCLC), urothelial carcinoma, and metastatic breast cancer. 140 , 141 , 142 , 143 Additionally, other anti‐TROP‐2 ADCs such as SKB264 and datopotamab deruxtecan have shown potent antitumor activity in preclinical studies. 144 , 145 Datopotamab deruxtecan, composed of a recombinant humanized anti‐TROP2 IgG1 mAb conjugated with a Topo I inhibitor (DXd) via a tetrapeptide‐based linker, is a TROP‐2 ADC with a cleavable tetrapeptide linker and a more potent topoisomerase inhibitor payload compared with SG.…”

“… 147 , 148 In patients with hormone receptor‐positive/HER2‐negative endocrine‐resistant metastatic breast cancer, SG showed a longer PFS compared with chemotherapy [5.5 months (95% CI, 4.2–7.0) vs. 4.0 months (95% CI, 3.1–4.4); HR 0.66, p = 0.0003)]. 149 In the TROPHY‐U‐01 phase II trial (NCT03547973), SG was effective in patients with metastatic urothelial carcinoma who had progressed on two prior lines of therapy, 142 , 150 with an ORR of 27% (95% CI, 19.5–36.6) at a median follow‐up of 9.1 months, and promising median PFS (5.4 months, 95% CI, 3.5–7.2 months) and OS (10.9 months, 95% CI, 9.0–13.8 months), respectively. These results led to US FDA approval of SG as a treatment option for patients with locally advanced or metastatic urothelial cancer who had previously received platinum‐based chemotherapy or immune checkpoint inhibitors.…”

Genomic Profiling and Molecular Characterisation of Metastatic Urothelial Carcinoma

“…The results obtained with ADCs in subsequent lines are also remarkable: (I) Enfortumab vedotin (a fully human monoclonal antibody specific for nectin-4 linked to monomethyl auristatin E) was proved to be superior to chemotherapy in patients with mUC that progressed after platinum-based chemotherapy and ICI [9]; (II) Sacituzumab govitecan (a TROP-2-directed antibody-drug conjugate with showed notable activity in patients affected by mUC that progressed after platinum-based chemotherapy and ICI in a phase II trial [13], and a phase III trial is ongoing; (III) Trastuzumab deruxtecan (an immunoconjugate composed by an antibody directed against HER2 linked to a topoisomerase I inhibitor) showed efficacy in HER2-expressing UC in a phase II basket trial [14].…”