Sean E. Harper, MD
A phase III study of the investigational peptibody trebananib has met its primary endpoint of an improvement in progression-free survival (PFS) after early results 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, according to information released by the drug’s manufacturer, Amgen.
Trebananib (formerly AMG 386) is a peptibody—an engineered protein with properties of both peptides and antibodies—that is 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.
“The TRINOVA-1 study is the first of three phase III trials designed to evaluate the safety and efficacy of trebananib in patients with ovarian cancer,” said Sean E. Harper, MD, executive vice president of Research and Development at Amgen, in a statement. “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.”
In the TRINOVA-1 trial, a global, multicenter, randomized, double-blind, placebo-controlled study, 919 women with recurrent partially platinum-sensitive or platinum-resistant epithelial ovarian, primary peritoneal, or fallopian tube cancer were randomized to receive 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.
The investigators 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 compared with 5.4 months in the placebo arm.
According to Amgen, the data on overall survival (OS) in the TRINOVA-1 study is not expected to mature until sometime in 2014. In a statement, the company 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.
Two other phase III studies, TRINOVA-2 and TRINOVA-3, are underway to continue to assess the efficacy of trebananib in ovarian cancer. In the TRINOVA-2 trial, trebananib is being given in combination with pegylated liposomal doxorubicin (PLD) to determine whether the combination is superior to PLD alone in recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. The TRINOVA-3 trial is a placebo-controlled trial evaluating trebananib in combination with paclitaxel and carboplatin as a first-line treatment for epithelial ovarian, primary peritoneal, or fallopian tube cancer.