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

Author(s): Apolo AB,  Karzai FH,  Trepel JB,  Alarcon S,  Lee S,  Lee MJ,  Tomita Y,  Cao L,  Yu Y,  Merino MJ,  Madan RA,  Parnes HL,  Steinberg SM,  Rodriguez BW,  Seon BK,  Gulley JL,  Arlen PM,  Dawson NA,  Figg WD,  Dahut WL

Journal: Clin Genitourin Cancer

Date: 2017 Feb

Major Program(s) or Research Group(s): PUCRG

PubMed ID: 27328856

PMC ID: PMC6583922

Abstract: BACKGROUND: In this trial we 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 2 weeks on days 1 and 15 of each 28-day cycle. The primary end point was progression-free survival (PFS) at 6 months. Secondary end points included safety, toxicity, and overall survival (OS). CD105 expression was evaluated using 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% confidence interval (CI), 1.8-2.1 months). This met the criterion for ending accrual on the basis of 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 = .26) or presence of lymph nodes (P = .64). Baseline levels of regulatory T and B cells, CEPs, and changes in CEC level after TRC105 exhibited trends toward an association with PFS or OS. CTCs pre- and post-TRC105 were detected in 4 of 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.