Open Label Dose-Finding Study of TRC105 Plus Capecitabine for Metastatic Breast Cancer

All patients were required to sign a consent form prior to undertaking any study-related
procedures. Prospective patients were screened to determine if they qualified for the study
within 28 days of enrollment. Patients who qualified received TRC105 i.v. over 1 to 4 hours
on Day 1, Day 4, Day 8 and Day 15 of the initial 21-day cycle and Day 1, Day 8 and Day 15 of
every subsequent 21-day cycle in combination with 1000 mg/m2 capecitabine BID for 14 days of
each 21-day cycle. Those who tolerated TRC105 without any infusion reactions were eligible
for reduced infusion durations. After 3 cycles of treatment, patients who demonstrated a
response of complete response (CR), partial response (PR) or stable disease (SD) were
eligible for additional treatment for up to six months (9 total cycles). Upon discussion with
TRACON, patients judged by the Principal Investigator to be benefiting from treatment were
able to continue treatment on this protocol beyond six months.

Toxicities were graded according to the NCI CTCAE Version 4.0. Patients who exited the study
for reasons other than drug-related toxicity prior to completion of the first 21-day cycle
were replaced. Intra-patient dose escalation was not allowed.

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