Study to Evaluate Mechanisms of Acquired Resistance to Panitumumab

- Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum; - Subjects with wild-type KRAS tumor status confirmed by an Amgen approved central laboratory assessment or an experienced local laboratory assessment of archival tumor tissue (preferably from the primary tumor); - Radiographic evidence of disease progression while on or ≤ 6 months after completion of treatment with irinotecan- and oxaliplatin- or oxaliplatin-based chemotherapy for mCRC; - Radiographic measurement of tumor burden done within 28 days prior to Day 1 (start of treatment with investigational product); - At least 1 uni-dimensionally measurable lesion ≥ 20 mm using conventional computed tomography (CT) or magnetic resonance imaging (MRI) or ≥ 10 mm by spiral CT scan per modified RECIST v1.0. 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; - At least 1 tumor (preferably a metastasis or unresected primary tumour) that is amenable to core biopsy, as determined by the clinician who will perform the biopsy; - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; - A life expectancy estimate of ≥ 3 months; - Willing to undergo two serial core biopsy procedures of tumors (metastasis or unresected primary); - other criteria may apply

- History of other primary cancer, unless: -- Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before enrollment and felt to be at low risk for recurrence by the treating physician, - Adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of disease, -- Adequately treated cervical carcinoma in situ without evidence of disease, -- Prostatic intraepithelial neoplasia without evidence of prostate cancer; - History of prior or concurrent central nervous system (CNS) metastases; - Prior treatment with anti-EGFR (eg, panitumumab, cetuximab or small molecule inhibitors (eg, erlotinib, gefitinib); - Prior treatment with monoclonal antibodies directed against insulin-like growth factor-1 receptor (IGF-1R) or small molecule inhibitors directed against IGF-1R; - Use of systemic chemotherapy or radiotherapy ≤ 21 days before enrollment. Subjects must have recovered from acute toxicities related to radiotherapy; - Use of any antibody therapy (eg, bevacizumab) ≤ 42 days before enrolment; - Use of anti-tumor therapies including prior experimental agents or approved anti-tumor small molecules ≤ 30 days before enrolment; - Known allergy or hypersensitivity to any component of panitumumab, irinotecan, or AMG 479; - Known uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) polymorphisms predisposing to increased irinotecan toxicity; - History of irinotecan intolerance that may interfere with planned treatment; - History of interstitial lung disease (eg, pneumonitis, pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest CT scan; - Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrolment; - Active inflammatory bowel disease or other active bowel disease causing chronic diarrhea (defined as ≥ grade 2 per Common Terminology Criteria for Adverse Events (CTCAE) version 3.0); - Known positive test(s) for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or chronic active hepatitis B infection; - Major surgical procedure ≤ 28 days before enrollment or minor surgical procedure ≤ 14 days before enrollment. Subjects must have recovered from surgery related toxicities. Core biopsy, central venous catheter placement, fine needle aspiration, thoracentesis, or paracentesis is not considered a major or minor surgical procedure; - Other investigational procedures or drugs (ie, participation in another clinical study) ≤ 30 days before enrolment; - other criteria may apply