A Phase II Clinical Trial of TRC105 (Anti-Endoglin Antibody) in Adults with Advanced/Metastatic Urothelial Carcinoma

Abstract Background This trial assessed the efficacy and tolerability of TRC105, a chimeric monoclonal antibody that targets CD105 (endoglin) in patients with advanced, previously treated urothelial carcinoma (UC). Patients and Methods Patients received TRC105 15 mg/kg every two weeks on days 1 and 15 of each 28-day cycle. The primary endpoint was progression-free survival (PFS) at 6 months. Secondary endpoints included safety, toxicity, and overall survival (OS). CD105 expression was evaluated by immunohistochemistry (IHC) in a separate cohort of 50 UC patients. Biomarker studies included immune subsets, circulating tumor cells (CTCs), circulating endothelial cells (CECs), circulating endothelial progenitor cells (CEPs), and osteopontin. Results Of 13 patients enrolled, 12 were evaluable for OS and PFS. The 3-month PFS probability was 18.2% (median PFS 1.9 months (95% CI: 1.8–2.1 months). This met the criterion for ending accrual based on the 2-stage design. Median OS was 8.3 months (95% CI: 3.3–17.0 months). IHC for CD105 scores was not associated with T stage ( P = 0.26) or presence of lymph nodes ( P = 0.64). Baseline levels of regulatory T and B cells, CEPs, and changes in CEC level after TRC105 exhibited trends towards an association with PFS or OS. CTCs pre- and post-TRC105 were detected in 4/4 patients. Conclusion Although TRC105 was well tolerated, it did not improve 6-month PFS in heavily pretreated patients with advanced UC. CD105 staining was present in 50% of UC tumors at different intensities. Our observations on the pharmacodynamic significance of immune subsets, CECs, and CTCs warrant further study.