Top-line secondary endpoint results from the phase III TRINOVA-1 trial in women with recurrent platinum-resistant ovarian cancer did not demonstrate a statistically significant improvement in overall survival. The study evaluated trebananib plus paclitaxel versus placebo plus paclitaxel.
Median overall survival was 19.3 months in the trebananib arm versus 18.3 months in the control arm. The data will be submitted to a future medical conference and for publication according to Amgen, trebananib’s sponsor.
In the previously reported primary endpoint analysis, the data demonstrated a statistically significant difference in progression-free survival for trebananib. In that analysis, patients treated with trebananib showed a 34 percent reduction in the risk of disease progression or death (HR = 0.66, 95 percent CI, 0.57, 0.77, p<0.001). The median progression-free survival was 7.2 months in the trebananib arm versus 5.4 months in the control arm.
“While the overall survival results of the TRINOVA-1 study are disappointing, this 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 Harper, executive vice president of Research and Development at Amgen. “We continue to explore the potential of trebananib’s novel anti-tumor mechanism of action in other cancer settings.”
TRINOVA-1 enrolled over 900 women with recurrent partially platinum-sensitive or -resistant (platinum-free interval of 12 months or less) epithelial ovarian, primary peritoneal or fallopian tube cancer. Patients were randomized 1:1 to receive either 15 mg/kg of intravenous trebananib weekly plus 80 mg/m2 of intravenous paclitaxel weekly (three weeks on, one week off) or weekly intravenous placebo plus 80 mg/m2 of intravenous paclitaxel weekly (three weeks on, one week off).
In the trebananib arm, the most frequently reported adverse events were localized edema, nausea and alopecia. The rate of discontinuation of investigational product due to adverse events was 20 percent in the trebananib arm versus seven percent in the control arm. No new safety signals were detected.
Trebananib is an investigational peptibody designed to inhibit the angiopoietin axis. Trebananib is designed to bind to both angiopoietin-1 and -2 (Ang1 and Ang2), and inhibit their interaction with the Tie2 receptor. The angiopoietins are also involved in lymphangiogenesis, the formation of new lymphatic vessels, which plays a key role in tumor metastasis.
Data from another trial in the recurrent platinum-resistant population (TRINOVA-2) is expected in Q4 2014. Data from a trial evaluating trebananib in combination with first-line chemotherapy treatment for patients with ovarian cancer (TRINOVA-3) is expected in 2015.
