Study Failed to Meet Secondary Endpoint of Overall Survival
THOUSAND OAKS, Calif., Nov. 4, 2014 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced the top-line secondary endpoint results of overall survival from the Phase 3 TRINOVA-1 trial in women with recurrent platinum-resistant ovarian cancer. The study, which evaluated trebananib plus paclitaxel versus placebo plus paclitaxel, did not demonstrate a statistically significant improvement in overall survival. 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.
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 3 trials designed to evaluate the safety and efficacy of trebananib in patients with ovarian cancer," said Sean E. Harper, M.D., 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."
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.
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.
TRINOVA-1 Trial Design (NCT01204749)
TRINOVA-1 (A Study of AMG 386 or Placebo, in Combination With Weekly Paclitaxel Chemotherapy, as Treatment for Ovarian Cancer, Primary Peritoneal Cancer and Fallopian Tube Cancer) is a Phase 3 global, multicenter, randomized, double-blind, placebo-controlled study evaluating trebananib in 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).
Other ongoing Phase 3 studies of trebananib include TRINOVA-2 and TRINOVA-3. TRINOVA-2 is evaluating whether trebananib plus pegylated liposomal doxorubicin (PLD) is superior to placebo plus PLD as measured by progression-free survival in recurrent epithelial ovarian, primary peritoneal or fallopian tube cancer. TRINOVA-3 is evaluating trebananib or placebo in combination with paclitaxel and carboplatin in the first-line treatment of epithelial ovarian, primary peritoneal or fallopian tube cancer.
Trebananib is an investigational peptibody designed to inhibit the angiopoietin axis. The angiopoietin axis is involved in angiogenesis, a process used by the body to grow new blood vessels, which is also involved in the pathogenesis of several diseases. Trebananib is designed to bind to both angiopoietin-1 and -2 (Ang1 and Ang2), and inhibit their interaction with the Tie2 receptor.1,2,3 Ang1 and Ang2 each mediate separate actions upon binding with Tie2.4,5 Ang1 impacts vessel quality while Ang2 influences vessel quantity. The angiopoietins are also involved in lymphangiogenesis, the formation of new lymphatic vessels, which plays a key role in tumor metastasis.6
About Ovarian Cancer
About 21,980 women will be diagnosed with ovarian cancer in the U.S. in 2014 and about 14,270 women will die from ovarian cancer.7 More than 70 percent of women with ovarian cancer will present with advanced disease at diagnosis and up to 80 percent of them will experience disease recurrence and eventually die from their disease.8,9
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.
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1 Herbst R.S., Expert Opin Emerg Drugs. 2006;11:635-650.
2 Carmeliet P., Jain R.K., Nature. 2000;407:249-257.
3 Folkman J., Nat Rev Drug Discov. 2007;6:273-286.
4 Falcon B.L., Hashizume H., Koumoutsakos P., et al., Am J Pathol. 2009;175:2159–2170.
5 Ahmad S.A., Liu W., Jung Y.D., et al., Cancer Res. 2001;61:1255-1259.
6 Huang H., Bhat A., Woodnutt G., et al., Nat Rev Cancer. 2010;10:575-585.
7 American Cancer Society, "What are the key statistics about ovarian cancer?" http://www.cancer.org/cancer/ovariancancer/detailedguide/ovarian-cancer-key-statistics. Accessed October 2, 2014
8 Martin L.P., Semin Oncol. 2009.
9 NCCN Ovarian Cancer 2013 Guidelines.