AMG 386 Phase 2 Open-Label Renal Cell Carcinoma (RCC) study 1st Line or After Cytokine Failure in Combination with Sunitinib

- Subjects must have a histologically confirmed metastatic renal cell cancer (RCC) with a clear cell component - Low or intermediate risk according to the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic risk classification - Measurable disease with at least one unidimensionally measurable lesion per Response Evaluation Criteria in Solid Tumor (RECIST) guidelines with modifications - Adequate organ and hematological function as evidenced by laboratory studies conducted at Screening - Eastern Cooperative Oncology Group (ECOG) of 0 or 1

Disease related - Known history of central nervous system metastases. - Previous treatment (excluding surgery, prior cytokine-based immunotherapy and palliative radiotherapy) for advanced or metastatic renal cell carcinoma - Focal radiation therapy for palliation of pain from bony metastases within 14 days of enrollment. Medications - Currently or previously treated with sunitinib or other small molecule inhibitors of vascular endothelial growth factor (VEGF) - Currently or previously treated with agents that neutralizing VEGF - Currently or previously treated with AMG 386, or other molecules that inhibit the angiopoietins or Tie2 receptor - Currently or previously treated with agents inhibiting the mammalian target of rapamycin (mTOR) - Current or within 30 days prior to enrollment treatment with immune modulators - Concomitant or previous use within 30 days prior to enrollment of any strong inducer of CYP3A4 - Concomitant or previous use of amiodarone within 6 months prior to enrollment General medical - Clinically significant cardiovascular disease within 12 months prior to enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication, percutaneous transluminal coronary angioplasty/stent - Major surgery within 28 days prior to enrollment or still recovering from prior surgery - Uncontrolled hypertension as defined as diastolic > 90 mmHg OR systolic >150 mmHg. The use of anti-hypertensive medications to control hypertension is permitted. Other - Other investigational procedures are excluded - Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s), or subject is receiving other investigational agent(s) Other inclusion/exclusion criteria may apply, per protocol.