TY - JOUR
T1 - A Phase I, open-label study of Trebananib combined with sorafenib or sunitinib in patients with advanced renal cell carcinoma
AU - Hong, David S.
AU - Gordon, Michael S.
AU - Samlowski, Wolfram E.
AU - Kurzrock, Razelle
AU - Tannir, Nizar
AU - Friedland, David
AU - Mendelson, David S.
AU - Vogelzang, Nicholas J.
AU - Rasmussen, Erik
AU - Wu, Benjamin M.
AU - Bass, Michael B.
AU - Zhong, Zhandong D.
AU - Friberg, Gregory
AU - Appleman, Leonard J.
N1 - Funding Information:
This work was supported by Amgen Inc .
Funding Information:
David S. Hong has research funding and Speakers Bureau support from Amgen . Razelle Kurzrock has research/grant funding from Amgen . Nicholas J. Vogelzang participates in a data safety and monitoring board for Amgen. Erik Rasmussen, Benjamin M. Wu, Michael B. Bass, Zhandong D. Zhong, and Gregory Friberg are employees of Amgen, and hold stocks or stock options in Amgen. All other authors state that they have no conflicts of interest.
PY - 2014/6
Y1 - 2014/6
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Angiopoietins
KW - Targeted therapies
KW - Tie2 receptor
KW - Vascular growth factor receptor
UR - http://www.scopus.com/inward/record.url?scp=84900319173&partnerID=8YFLogxK
U2 - 10.1016/j.clgc.2013.11.007
DO - 10.1016/j.clgc.2013.11.007
M3 - Article
C2 - 24365125
AN - SCOPUS:84900319173
SN - 1558-7673
VL - 12
SP - 167-177.e2
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
IS - 3
ER -