A Phase I, Open-Label Study of Trebananib Combined With Sorafenib or Sunitinib in Patients With Advanced Renal Cell Carcinoma

Trebananib prevents tumor angiogenesis by binding to angiopoietin 1 and 2. This phase I study examined trebananib administered once everyweek in combination with the vascular endothelial growth factor pathway inhibitors sorafenib or sunitinib in patients with advanced renal cell carcinoma (RCC). Both treatment combinations appeared to have acceptable toxicity profiles consistent with sorafenib or sunitinib monotherapy and show evidence of antitumor activity. Background: Trebananib, an investigational peptibody, binds to angiopoietin 1 and 2, thereby blocking their interaction with Tie2. Patients and Methods: This open-label phase I study examined trebananib 3 mg/kg or 10 mg/kg intravenous (I. V.) once weekly plus sorafenib 400 mg twice per day or sunitinib 50 mg once per day in advanced RCC. Primary end points were adverse event incidence and pharmacokinetics. Results: Thirty-seven patients were enrolled. During trebananib plus sorafenib administration (n = 17), the most common treatment-related adverse events (TRAEs) included rash (n = 12; 71%), diarrhea (n = 12; 71%), hypertension (n = 11; 65%), and fatigue (n 11; 65%); grade >= 3 TRAEs (n = 7; 41%); and 2 patients (12%) had peripheral edema. During trebananib plus sunitinib administration (n = 19), the most common TRAEs included diarrhea (n = 14; 74%), fatigue (n = 13; 68%), hypertension (n 11; 58%), and decreased appetite (n = 11; 58%); grade >= 3 TRAEs (n = 13; 68%); and 8 (42%) patients had peripheral edema. Trebananib did not appear to alter the pharmacokinetics of sorafenib or sunitinib. No patient developed anti-trebananib antibodies. Objective response rates were 29% (trebananib plus sorafenib) and 53% (trebananib plus sunitinib). Conclusion: The toxicities of trebananib 3 mg/kg or 10 mg/kg I. V. plus sorafenib or sunitinib in RCC were similar to those of sorafenib or sunitinib monotherapy, with peripheral edema being likely specific to the combinations. Antitumor activity was observed. (C) 2014 Elsevier Inc. All rights reserved.