Ovarian Cancer Drug Disappoints in Late-Stage Trial

An experimental ovarian cancer treatment failed to demonstrate statistically significant improvements in overall survival during a phase 3 trial.

Developed by Amgen, trebananib acts as a peptibody designed to inhibit the angiopoietin axis, which is involved in angiogenesis and in the pathogenesis of several diseases. Despite the setback in the recent trial, Amgen remains hopeful concerning the drug’s potential in ovarian cancer.

"While the overall survival results of the TRINOVA-1 study are disappointing, this study is the first of 3 phase 3 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 press release. "We continue to explore the potential of trebananib's novel anti-tumor mechanism of action in other cancer settings."

Trebananib is designed to bind to both angiopoietin-1 and -2 to inhibit interaction with the Tie2 receptor. The angiopoietins also play a key role in tumor metastasis.

In a previously reported study, trebananib demonstrated a statistically significant difference in progression-free survival. During that trial, patients treated with trebananib exhibited a 34% reduction in the risk of disease progression or death and also achieved a median progression-free survival of 7.2 months, compared with 5.4 months in the control arm.

For the current randomized, double-blind, placebo-controlled phase 3 trial, researchers evaluated trebananib in more 900 women with recurrent partially platinum-sensitive or -resistant epithelial ovarian, primary peritoneal, or fallopian tube cancer. The patients were randomized to receive either 15 mg/kg of intravenous trebananib per week, in addition to 80 mg/m² of intravenous paclitaxel weekly for a duration of 3 weeks on and 1 week off, or an intravenous placebo with 80 mg/m² of intravenous paclitaxel weekly for a duration of 3 weeks on and 1 week off.

Median overall survival was 19.3 months in the trebananib cohort, compared with 18.3 months in the control cohort.

The most frequently reported adverse events in the trebananib arm were localized edema, nausea, and alopecia. The discontinuation rate for trebananib due to adverse events was 20%, versus 7% in the control arm.

Data from another trial in the recurrent platinum-resistant population is expected during the fourth quarter of 2014, while data from a trial evaluating trebananib combined with first-line chemotherapy treatment for ovarian cancer patients is due in 2015.