Inclusion Criteria:

1. Histologically confirmed advanced renal cell carcinoma that has progressed following
treatment with at least one multi-targeted tyrosine kinase inhibitor that targets the
VEGF receptor (e.g., sunitinib, pazopanib, sorafenib, tivozanib). Prior
immunotherapy, bevacizumab or mTOR inhibitor treatment is allowed. Prior axitinib is
allowed if the drug was not discontinued for toxicity.

2. No history of other carcinoma within the last five years, and/or where the risk of
recurrence is known to be under 5%

3. Measurable disease by RECIST criteria

4. Age of 18 years or older

5. ECOG performance status ≤ 1

6. Resolution of all acute adverse events resulting from prior cancer therapies to NCI
CTCAE grade ≤ 1 or baseline (except alopecia)

7. Willingness and ability to consent for self to participate in study

Exclusion Criteria:

1. Prior treatment with TRC105

2. Current treatment on another therapeutic clinical trial

3. Receipt of a small molecule anticancer agent, including an investigational anticancer
small molecule, within 14 days of starting study treatment

4. Receipt of a large molecule anticancer agent (e.g., antibody), including an
investigational anticancer antibody, within 28 days of starting study treatment

5. Prior surgery (including open biopsy) within 28 days of starting the study treatment
or the anticipated need for a major surgical procedure within the next six months

6. Prior radiation therapy within 28 days of starting the study treatment, except
radiation therapy for bone metastases is permitted up to 14 days of starting
treatment

7. Minor surgical procedures such as fine needle aspiration, Mediport placement or core
biopsy within 7 days of study treatment

8. Uncontrolled chronic hypertension defined as systolic > 150 or diastolic > 90 despite
optimal therapy (initiation or adjustment of BP medication prior to study entry is
allowed provided that the average of 3 BP readings at a visit prior to enrollment is
< 140/90 mm Hg)

9. Symptomatic ascites or pericardial or pleural effusion

10. History of brain involvement with cancer, spinal cord compression, or carcinomatous
meningitis, or new evidence of brain or leptomeningeal disease. Patients with
radiated or resected lesions are permitted, provided the lesions are fully treated
and inactive, patients are asymptomatic, and no steroids have been administered for
at least 30 days.

11. Angina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient
ischemic attack, arterial embolism, pulmonary embolism, Venous thrombosis, including
pulmonary embolism and deep venous thrombosis (unless adequately anticoagulated
without warfarin for more than two weeks), PTCA or CABG within the past 6 months

12. Active bleeding or pathologic condition that carries a high risk of bleeding (e.g.
hereditary hemorrhagic telangiectasia). Patients who have been uneventfully
anti-coagulated with low molecular weight heparin are eligible.

13. Thrombolytic use (except to maintain i.v. catheters) within 10 days prior to first
day of study therapy

14. Cardiac dysrhythmias of NCI CTCAE grade ≥ 2 within the last 28 days

15. Known active viral or nonviral hepatitis or cirrhosis

16. History of hemorrhage or hemoptysis (> ½ teaspoon bright red blood) within 6 months
of starting study treatment

17. Pregnancy or breastfeeding. Female patients must be surgically sterile (i.e.:
hysterectomy) or be postmenopausal, or must agree to use effective contraception
during the study and for 3 months following last dose of TRC105.