Inclusion Criteria:

101 Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum 102 Radiographically documented disease progression per modified RECIST during or following treatment with fluoropyrimidine, irinotecan, and/or oxaliplatin chemotherapy for Metastatic Colorectal Cancer. Progressive disease must be documented during or ≤ 6 months after the last dose of the most recent chemotherapy regimen prior to enrollment.

103 At least 1 uni-dimensionally measurable lesion measuring ≥ 20 mm in one dimension per modified RECIST. Lesion must not be chosen from a previously irradiated field, unless there has been documented disease progression in that field after irradiation and prior to enrollment. All sites of disease must be evaluated.

104 Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 105 Available archived paraffin-embedded tumor tissue from the primary tumor or metastasis for submission to the central laboratory 106 Man or woman ≥ 18 years of age at the time of enrollment 107 Hematologic function within the following limits:

• Absolute neutrophil count (ANC) > 1.0 x 109 cells/L
• Platelets ≥ 100 x 109/L 108 Renal function within the following limits:
• Creatinine < 2.0 mg/dL 109 Hepatic function within the following limits:
• Aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases)
• Alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases)
• Bilirubin ≤ 2 x ULN 110 Metabolic function within the following limits:
• Amylase ≤ 2 x ULN
• Lipase ≤ 2 x ULN
• Magnesium ≥ lower limit of normal 111 Negative pregnancy test ≤ 72 hours before enrollment (for woman of childbearing potential only) 112 Subject must have received 1, 2, or 3 prior chemotherapy regimens for Metastatic Colorectal Cancer 113 Competent to comprehend, sign, and date the IEC/IRB approved written informed consent

Exclusion Criteria:

201 History of other primary cancer, unless:

• Curatively resected non-melanomatous skin cancer
• Curatively treated cervical carcinoma in situ

• Other primary solid tumor curatively treated with no known active disease present and no treatment administered for ≥ 5 years before enrollment 202 Prior treatment with anti-EGFr inhibitors (eg, cetuximab, erlotinib, gefitinib), unless treatment was received in the adjuvant setting ≥ 6 months before enrollment 203 Use of systemic chemotherapy and radiotherapy ≤ 30 days before enrollment 204 Use of prior anti-tumor therapies with a short serum half-life (less than 1 week) including prior experimental agents or approved anti-tumor small molecules ≤ 30 days before enrollment 205 Use of anti-tumor therapies with a longer serum half-life (eg, bevacizumab) including prior experimental or approved protein/antibodies ≤ 42 days before enrollment 206 Any investigational agent or therapy ≤ 30 days before enrollment 207 Known allergy or hypersensitivity to any component of panitumumab and/or AMG 655 208 History of or known presence of central nervous system (CNS) metastases 209 History of interstitial lung disease (eg, pneumonitis, pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computerized tomography (CT) scan 210 Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrollment 211 Active inflammatory bowel disease or other active bowel disease causing chronic diarrhea (defined as ≥ CTC grade 2 [CTCAE version 3.0]) 212 Known positive test for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or chronic hepatitis B infection 213 Any co-morbid disease or condition that could increase the risk of toxicity (eg, significant ascites, significant pleural effusion) 214 Any uncontrolled concurrent illness (eg, infection, bleeding) or history of any medical condition that may interfere with the interpretation of the study results 215 Major surgical procedure (requiring general anesthesia) ≤ 28 days or minor surgical procedure (excluding central venous catheter placement) ≤ 14 days before enrollment. Subjects must have recovered from surgery related toxicities.

  216 Other investigational procedures are excluded 217 Subject is currently pregnant or breast feeding 218 Man or woman of childbearing potential who is not willing to use adequate contraceptive precautions during treatment and for 6 months (for women) or 1 month (for men) after the last investigational product administration. Adequate contraceptive precautions includes double barrier contraceptive methods (eg, diaphragm and condom) or abstinence.

  219 Previously enrolled into this study 220 Subject unwilling or unable to comply with study requirements