Amgen (Nasdaq: AMGN) today announced results from a small, randomized, placebo-controlled Phase 2 study indicating that adding AMG 479 to gemcitabine improved overall survival at six months (primary endpoint) and progression-free survival in patients with metastatic pancreatic cancer. The study, which also included a separate arm of conatumumab plus gemcitabine, is being presented in a Poster Discussion at the 2010 American Society of Clinical Oncology (ASCO) Annual Meeting. (Abstract Number: 4035)
AMG 479 is an investigational fully human monoclonal antibody that targets type 1 insulin-like growth factor receptor (IGF-1R). Signaling through IGF-1R plays an important role in the regulation of cell growth and survival. Conatumumab is an investigational fully human monoclonal antibody agonist that targets death receptor 5 (DR-5) and induces apoptosis - programmed cell death - in sensitive tumor cells.
"Pancreatic cancer has the worst survival of any solid tumor, and novel approaches to treat this disease are needed," said Dr. Hedy Kindler, M.D., associate professor of Medicine, medical director, Gastrointestinal Oncology and director, Mesothelioma Program, University of Chicago Medical Center. "In this study, AMG 479 demonstrated promising activity, extending progression-free survival three months and overall survival nearly three months compared to gemcitabine alone."
Patients were randomized to receive AMG 479 plus gemcitabine.
The addition of AMG 479 to gemcitabine resulted in an overall survival rate at six months of 57 percent versus 50 percent with gemcitabine alone (95 percent CI, 41 - 70) and 39 percent versus 23 percent at 12 months (95 percent CI, 25 – 54). Median overall survival was 8.7 months versus 5.9 months in the gemcitabine arm (95 percent CI, 5.3 – 12.2). Patients receiving AMG 479 also experienced longer progression-free survival of 5.1 months versus 2.1 months (95 percent CI, 2.8 - 5.8).
The study also showed evidence of anti-tumor activity with conatumumab. Patients in the conatumumab arm experienced an overall survival rate at six months of 59 percent versus 50 percent (95 percent CI, 42 - 73) compared to gemcitabine alone and 20 percent versus 23 percent at 12 months (95 percent CI, 9 – 34). Patients receiving conatumumab experienced progression-free survival of 4.0 months versus 2.1 months compared to gemcitabine alone (95 percent CI, 3.3 – 5.0).
Both AMG 479 and conatumumab in combination with gemcitabine were tolerable. Grade 3 or higher adverse events observed included neutropenia (AMG 479/conatumumab/ placebo arm percentages 18/22/13), thrombocytopenia (15/17/8), abdominal pain (8/17/13), and fatigue (13/12/5).
Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. In 2009, there were more than 42,000 new cases of pancreatic cancer and 35,000 deaths from the disease. Because diagnosis and intervention occur late in the course of this disease, the vast majority of patients already have metastatic disease at the time of diagnosis.
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