Inclusion Criteria:

- Histologically proven advanced solid cancer for which curative therapy is not
available (Part 1 only)

- Histologically proven metastatic Her-2-negative breast cancer (Part 2 only)

- Measurable disease by RECIST 1.1 criteria (Part 2 only)

- Willing and able to consent for self to participate in study

- Progressive or recurrent disease after prior systemic chemotherapy regimen

- Age ≥ 18 years

- ECOG performance status of 0 or 1

- Resolution of all acute toxic effects of prior therapy to NCI CTCAE Grade ≤ 1 or
baseline (except alopecia)

- Adequate organ function

Exclusion Criteria:

- Prior treatment with more than one systemic chemotherapy regimen for metastatic
disease.

- Prior treatment with TRC105

- History of hypersensitivity reaction to antimetabolite therapy

- Receipt of an investigational agent within 28 days of starting study treatment

- Prior surgery (including open biopsy), radiation therapy or systemic therapy within
28 days of starting study treatment

- Minor surgical procedures within 14 days prior to first dose of TRC105

- History of brain metastasis, spinal cord compression, or carcinomatous meningitis, or
new evidence of brain or leptomeningeal disease

- Angina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient
ischemic attack, arterial embolism, pulmonary embolism, DVT, PTCA or CABG within the
past 6 months

- Uncontrolled chronic hypertension defined as systolic > 140 or diastolic > 90 despite
optimal therapy

- Past medical history of acquired or inherited coagulopathy including patients with
known hereditary hemorrhagic telangiectasia

- Thrombolytic or anticoagulant use (except to maintain i.v. catheters) within 10 days
prior to first dose with TRC105

- Cardiac dysrhythmias of NCI CTCAE Grade ≥ 2 within the last month

- Hemorrhage within 28 days of starting study treatment

- Unhealed wounds within 28 days of starting study treatment

- History of peptic ulcer disease or gastritis within the past 6 months, unless treated
for the condition and complete resolution has been documented by
esophagogastroduodenoscopy (EGD) within 28 days of starting study treatment

- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)
related illness

- Known active viral or nonviral hepatitis

- History of hypersensitivity reaction to human or mouse antibody products

- Lung cancer with central chest lesions

- Pregnancy or breastfeeding