A Phase 2 Study of ASONEP™ to Treat Unresectable and Refractory Renal Cell Carcinoma

• 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