A Phase I, open-label study of Trebananib combined with sorafenib or sunitinib in patients with advanced renal cell carcinoma

David S. Hong, Michael S. Gordon, Wolfram E. Samlowski, Razelle Kurzrock, Nizar Tannir, David Friedland, David S. Mendelson, Nicholas J. Vogelzang, Erik Rasmussen, Benjamin M. Wu, Michael B. Bass, Zhandong D. Zhong, Gregory Friberg, Leonard J. Appleman

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23 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)167-177.e2
JournalClinical Genitourinary Cancer
Volume12
Issue number3
DOIs
StatePublished - Jun 2014
Externally publishedYes

Keywords

  • Angiogenesis
  • Angiopoietins
  • Targeted therapies
  • Tie2 receptor
  • Vascular growth factor receptor

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