An investigational drug, AMG 386, combined with paclitaxel, demonstrated antitumor activity in a randomized Phase-II trial involving 161 patients with recurrent ovarian cancer. The updated results, now including data on overall survival, are being presented in a poster discussion at the 35th European Society for Medical Oncology (ESMO) Congress being held in Milan, Italy. (Abstract Number: 975PD)

“Treatment advances in ovarian cancer are desperately needed. Ovarian cancer remains the leading cause of gynecological cancer death in women with 5-year survival rates across all stages remaining low,” explained Ignace Vergote, MD, PhD, professor and chairman of the Department of Gynecologic Oncology, Leuven University Hospitals, Belgium. “The results of this Phase-II trial are promising.”

Patients in the trial were randomized to receive paclitaxel via IV weekly, three weeks on and one week off, plus weekly: AMG 386 at 10 mg/kg (Arm A, n=53), AMG 386 at 3 mg/kg (Arm B, n=53), or placebo (Arm C, n=55).

Overall survival in the 10 mg/kg arm was 22.5 months (HR = 0.60; 80 percent CI, 0.42 – 0.88; P=0.081) versus 20.4 months in the 3 mg/kg arm (HR = 0.77; 80 percent CI, 0.54 – 1.09; P=0.330) and 20.9 months in the placebo group. Median progression-free survival, the study’s primary endpoint, in the 10 mg/kg arm was 7.3 months versus 7.4 months in the 3 mg/kg arm and 5.0 months in the placebo group (HR [AMG 386 arms vs. placebo] = 0.64; 80 percent CI, 0.50 – 0.82; P=0.022). The objective response rate, per RECIST, was 37 percent in the 10 mg/kg arm versus 21 percent in the 3 mg/kg arm and 27 percent in the placebo group. Response rate measured by serum CA-125 levels, per the guidance from the Gynecologic Cancer Intergroup (GCIG), was 71 percent in the 10 mg/kg arm versus 58 percent in the 3 mg/kg arm and 28 percent in the placebo group.

Based in part on these results, the Company is initiating the TRINOVA-1 study, a Phase-III randomized, double blind trial evaluating AMG 386 administered in combination with weekly paclitaxel as treatment for ovarian, primary peritoneal, and fallopian tube cancers.

Advertisement #3

In the Phase-II trial, Grade-III or higher adverse events (AEs), where the difference in incidence was more than five percent in the AMG 386 arm than the placebo arm, included: hypokalemia (Arm A/B/C percentages 12/11/4), peripheral neuropathy (10/2/4), anorexia (2/6/0), neutropenia (8/9/4), and dyspnea (2/9/4).

Other grade-III or higher AEs of interest included thromboembolic events (arterial 2/2/0; venous 6/6/9). No grade 3 or higher hypertension was observed and there were no bowel perforations in patients treated with AMG 386. No treatment-related deaths occurred in the study.

AMG 386 is an investigational peptibody that is designed to block angiogenesis by inhibiting angiopoietin-1 and -2 (Ang1 and Ang2). Angiopoietins interact with the Tie2 receptor, which mediates vascular remodeling. Ang1 and Ang2 are thought to play opposing roles, and the maturation of blood vessels appears to be controlled by their precise balance.

Clinical Trials
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.

Advertisement #5