A phase III study of the investigational peptibody trebananib has met its primary endpoint of an improvement in progression-free survival.
A phase III study of the investigational peptibody trebananib has met its primary endpoint of an improvement in progression-free survival (PFS). Amgen released early results that showed an approximately one-third reduction of risk of progression or death in patients with recurrent ovarian cancer when the agent is combined with paclitaxel.
Trebananib (formerly known as AMG 386) is a peptibodyan engineered protein with properties of both peptides and antibodies—designed to inhibit the angiopoietin axis. Angiopoietins are associated with angiogenesis, the formation of blood vessels that can allow for tumors to grow. Other anti-angiogenesis agents, such as bevacizumab (Avastin), target vascular endothelial growth factor (VEGF), but trebananib is among the first to inhibit angiogenesis via angiopoietin. The drug works by binding to angiopoietin-1 and -2 (Ang1 and Ang2) and inhibiting their ability to interact with the Tie2 tyrosine-protein kinase receptor.
In the global, multicenter, randomized, double-blind, placebo-controlled TRINOVA-1 trial, 919 women with recurrent partially platinum-sensitive or platinum-resistant epithelial ovarian, primary peritoneal, or fallopian tube cancer were randomized to receive trebananib plus paclitaxel or placebo plus paclitaxel. Patients received either 15 mg/kg of intravenous trebananib weekly plus 80 mg/m2 of intravenous paclitaxel weekly for 3 weeks followed by 1 week off; or weekly intravenous placebo plus 80 mg/m2 of intravenous paclitaxel weekly for 3 weeks followed by 1 week off.
Sean E. Harper, MD, executive vice president of Research and Development at Amgen said in a statement that the TRINOVA-1 study is the first of three phase III trials that will evaluate trebananib in ovarian cancer.
“Angiopoietin inhibition has been a focus of research at Amgen, and these results suggest that the novel biology of trebananib may offer a promising approach for patients with ovarian cancer," Harper said.
Researchers observed a statistically significant difference in PFS, with the risk of disease progression or death reduced by 34% compared with patients who received the placebo (hazard ratio [HR] = 0.66; 95% CI, 0.57 - 0.77;P< .001). The median PFS was 7.2 months in the trebananib arm versus 5.4 months in the placebo arm.
Data on overall survival (OS) in the TRINOVA-1 study is not expected to mature until sometime in 2014. In a statement, Amgen noted that researchers observed an early imbalance of deaths favoring the placebo arm of the study. However, in a pre-planned interim analysis, an overall trend in OS favoring trebananib was observed.
The investigators reported that the most frequent adverse events in patients receiving trebananib were localized edema, nausea and alopecia. Adverse events were responsible for 20% of patients on the trebananib arm discontinuing treatment compared with 7% in the placebo arm.