This phase 1/2, multi-center, randomized, double-blind, placebo-controlled trial is designed to evaluate the efficacy and safety of AMG 655 when combined with mFOLFOX6 and bevacizumab compared with mFOLFOX6 and bevacizumab alone in subjects with previously untreated metastatic colorectal cancer (CRC).

The clinical benefit of AMG 655 in combination with mFOLFOX6 and bevacizumab will be measured by progression-free survival, objective response rate, time to response, duration of response, and overall survival. This study is also designed to evaluate the safety and tolerability of AMG 655 in combination with mFOLFOX6 and bevacizumab and to evaluate anti-AMG 655 antibody formation and the pharmacokinetics of AMG 655.

Inclusion Criteria:

• Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum.
• Subjects with measurable or unmeasurable disease
• Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
• Men or women at least 18 years of age
• Adequate hematologic, renal, hepatic and coagulation function

Exclusion Criteria:

• History or known presence of central nervous system (CNS) metastases
• Prior chemotherapy or other systemic therapy for advanced or metastatic CRC
• Any investigational agent or therapy for advanced or metastatic CRC
• Clinically significant cardiac disease
• Clinically significant peripheral neuropathy
• Active inflammatory bowel disease
• Recent gastrointestinal ulcer or hemorrhage
• Recent arterial thrombotic event or pulmonary embolus
• Recent history of clinically significant bleeding, bleeding diathesis, or coagulopathy
• Recent major surgical procedure or not yet recovered from major surgery