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Clin Genitourin Cancer. 2014 Jun;12(3):167-177.e2. doi: 10.1016/j.clgc.2013.11.007. Epub 2013 Nov 13.

A phase I, open-label study of trebananib combined with sorafenib or sunitinib in patients with advanced renal cell carcinoma.

Author information

1
Division of Cancer Medicine, Department of Investigational Cancer Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, TX. Electronic address: dshong@mdanderson.org.
2
Pinnacle Oncology Hematology, Scottsdale, AZ.
3
Comprehensive Cancer Centers of Nevada and US Oncology, Las Vegas, NV.
4
Division of Cancer Medicine, Department of Investigational Cancer Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, TX.
5
Hillman Cancer Center, Pittsburgh, PA.
6
Amgen Inc, Thousand Oaks, CA.

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.

KEYWORDS:

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

PMID:
24365125
PMCID:
PMC4754667
DOI:
10.1016/j.clgc.2013.11.007
[Indexed for MEDLINE]
Free PMC Article

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