A phase Ib/II, open-label, multicenter, randomized umbrella study evaluating the combination of atezolizumab with sacituzumab govitecan in patients with locally advanced or metastatic urothelial carcinoma and previously treated with a platinum-based treatment regimen (MORPHEUS-Urothelial Carcinoma)

BACKGROUND: MORPHEUS-UC (NCT03869190) is a signal-seeking, global, phase Ib/II, open-label, multicenter, randomized, umbrella study in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (mUC). Patients were randomly assigned to one of seven atezolizumab (anti-programmed death-ligand 1)-based treatment combinations or atezolizumab monotherapy. We report efficacy and safety results for atezolizumab + sacituzumab govitecan (trophoblast cell surface antigen-2-directed antibody conjugate) versus atezolizumab alone. PATIENTS AND METHODS: Eligible patients were checkpoint inhibitor-naïve and experienced disease progression or recurrence during or after ≤1 platinum-containing regimen. Primary endpoints were investigator-assessed objective response rate (ORR) and safety. Secondary efficacy endpoints included investigator-assessed progression-free survival (PFS), duration of response, disease control rate, and overall survival (OS). RESULTS: Fifteen patients received atezolizumab + sacituzumab govitecan; 30 received atezolizumab alone. The best confirmed ORR was 6.7% with atezolizumab + sacituzumab govitecan and 27.6% with atezolizumab. No improvement in ORR, PFS, or OS was seen with the addition of sacituzumab govitecan to atezolizumab. Most frequent treatment-related adverse events (TRAEs) were anemia, neutropenia, pruritus, nausea, and alopecia with atezolizumab + sacituzumab govitecan, and pruritus, decreased appetite, rash, and fatigue with atezolizumab. No grade 5 TRAEs occurred. CONCLUSIONS: The atezolizumab + sacituzumab govitecan efficacy and safety results suggest limited rationale for further development of this combination in platinum-experienced patients with locally advanced or mUC.