Inclusion Criteria:

- Unresectable, locally advanced recurrent or metastatic RCC

- Histological or cytological confirmation of clear cell RCC - core tissue biopsy of
either primary tumor or metastatic lesion with paraffin-embedded tissue specimens if
no prior nephrectomy

- Measurable disease by RECIST 1.1

- Had one prior therapy for unresectable RCC with a VEGF/VEGFR targeted therapy
(sunitinib, sorafenib, other VEGFR TKI or bevacizumab) - One prior treatment with an
mTOR inhibitor (everolimus, temsirolimus or sirolimus) for unresectable disease
permitted-Prior immunotherapy (immunomodulators such as cytokines, interleukins,
vaccines, etc.) such as IL-2 also permitted

- Male or non-pregnant, non-nursing female

- Life expectancy ≥3 months

- ECOG performance status of 0, 1 or 2

- Must not be receiving any concurrent anticancer therapy

- Baseline CT or MRI scans of measurable disease sites by RECIST 1.1 performed within 2
weeks of Day 0 - For subjects with bone metastases, baseline bone scan performed
within 4 weeks of study entry

- Adequate organ and immune function (within 7 days of Day 0):

Hemoglobin >9 g/dL−Absolute neutrophil count >1500 cells/uL without growth
factors−Platelet count ≥100x10^9/L without transfusion−Serum creatinine <2.0x ULN or
creatinine clearance >40 mL/min−Total bilirubin <1.5x ULN−AST/ALT <2.5x ULN (or <5.0x ULN
if liver metastases present)−INR and aPTT <1.5x ULN

- Subject lesions for arterial spin labeling (ASL) MRI ≥2.5cm by CT imaging

- Must understand, be able and willing to fully comply with study procedures

Exclusion Criteria:

- Prior treatment with >3 VEGF pathway and/or mTOR inhibitors for RC cancer

- History of other CNS disease (spinal cord compression, or evidence of symptomatic
brain or leptomeningeal carcinomatosis)

- Major surgery within 4 weeks of Day 0

- Radiation therapy within 4 weeks of baseline/infusion. Prior palliative radiation to
metastatic lesions is acceptable if there is at least one measurable, non-radiated
lesion

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection requiring parenteral antibiotics on Day 0

- Known or suspected intolerance or hypersensitivity to study materials or any
excipients

- Evidence of bowel obstruction because of theoretical possibility of GI perforation
with an anti-angiogenesis agent

- Severe hemorrhage within 4 weeks of screening

- History of GI perforation

- History of non-healing wounds including ulcer or delayed bone fractures

- Prolonged QTc interval on baseline ECG (>450 msec for males or >470 msec for
females), cardiac dysrhythmias including atrial fibrillation, torsade de pointes,
ventricular tachycardia or fibrillation, pathologic sinus bradycardia (<60 bpm),
heart block (excluding 1st degree block, being PR interval prolongation only),
congenital long QT syndrome or new ST segment elevation or depression or new Q wave
on ECG

- Secondary malignancy within the last 5 years, except for adequately-treated basal
cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ
cervical cancer

- Previously enrolled in an sonepcizumab study or into this study and subsequently
withdrawn

- History of alcohol or other substance abuse within the last year

- Use of corticosteroids or other immunosuppression (if taking systemic steroids [vs.
topical], at least 4 weeks must have passed since the last dose)

- Growth factors within 1 week of screening

- Serious medical conditions that might be aggravated by treatment or limit compliance

- Cerebrovascular accident or transient ischemic attack, or pulmonary embolism within 6
months prior to screening

- Participation in another clinical trial

- Other severe or intercurrent acute or chronic medical or psychiatric condition or
laboratory abnormality that may increase risk associated with study participation or
study drug administration