An Open-Label, Multicenter, Randomized Phase 2 Study Evaluating the Safety and Efficacy of Ramucirumab (IMC-1121B) Drug Product or IMC-18F1 in Combination With Capecitabine or Capecitabine Monotherapy, in Unresectable, Locally Advanced or Metastatic Breast Cancer Patients Previously Treated With Anthracycline and Taxane Therapy

Inclusion Criteria:

- The patient has histologically or cytologically confirmed breast cancer which at the
time of study entry is either Stage III disease not amenable to curative therapy or
Stage IV disease

- Has measurable or nonmeasurable disease

- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

- Has received prior anthracycline therapy

- Has received prior taxane therapy

- Patients with HER2-positive disease must have progressed on or following trastuzumab

- Patients with hormone receptor-positive disease must have progressed on or following
hormone therapy

- Has received ≤ 3 prior chemotherapy regimens in any setting (a regimen is defined as
any agent[s] that has been administered for more than 1 cycle; sequential
neoadjuvant/adjuvant treatment is considered 1 regimen)

- Has completed any prior radiotherapy ≥ 4 weeks prior to randomization

- Has completed any prior hormonal therapy ≥ 2 weeks prior to randomization

- Has AEs that have resolved to Grade ≤ 1 by the National Cancer Institute Common
Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v 4.0) from all
clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy,or
hormonal therapy

- Has adequate hematologic, coagulation, hepatic and renal function

- Does not have:

- cirrhosis at a level of Child-Pugh B (or worse) or

- cirrhosis (any degree) and a history of hepatic encephalopathy or ascites
resulting from cirrhosis and requiring ongoing treatment with diuretics and/or
paracentesis

- Has urinary protein is ≤ 1+ on dipstick or routine urinalysis; if urine protein ≥ 2+,
a 24-hour urine collection must demonstrate < 1000 mg of protein in 24 hours to allow
participation in the study

- Agrees to use adequate contraception during the study period and for 12 weeks after
the last dose of study medication

Exclusion Criteria:

- Has a concurrent active malignancy other than adequately treated nonmelanomatous skin
cancer, curatively treated cervical carcinoma in situ, or other noninvasive carcinoma
or in situ neoplasm. A patient with previous history of malignancy is eligible,
provided that there has been a disease-free interval for > 3 years

- Has a known sensitivity to capecitabine, any of its components, or other drugs
formulated with polysorbate 80

- Has a known sensitivity to 5-FU

- Has a known dihydropyrimidine dehydrogenase deficiency

- Has received prior capecitabine treatment for advanced breast cancer

- Has received investigational therapy within 2 weeks prior to randomization

- Has received bevacizumab within 4 weeks prior to randomization

- Has received more than 1 prior antiangiogenic agent for breast cancer

- Has a known sensitivity to agents of similar biologic composition as ramucirumab DP
or IMC-18F1, or other agents that specifically target VEGF

- Has an acute/subacute bowel obstruction or history of chronic diarrhea requiring
ongoing medical intervention

- Has a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders

- Has experienced a Grade ≥ 3 bleeding event within 3 months prior to randomization

- Is receiving prophylactic or therapeutic anticoagulation with warfarin or any other
oral anticoagulant

- Has an uncontrolled intercurrent illness, including, but not limited to uncontrolled
hypertension, symptomatic anemia, symptomatic congestive heart failure, unstable
angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric
illness/social situations, or any other serious uncontrolled medical disorder in the
opinion of the investigator

- Has experienced any arterial thrombotic or thromboembolic events, including, but not
limited to myocardial infarction, transient ischemic attack, or cerebrovascular
accident within 6 months prior to randomization

- Has brain metastases, uncontrolled spinal cord compression, or leptomeningeal disease

- Has an ongoing or active infection requiring parenteral antibiotic, antifungal, or
antiviral therapy

- Has received a prior allogeneic organ or tissue transplantation

- Has undergone major surgery within 4 weeks prior to randomization, or subcutaneous
venous access device placement within 7 days prior to randomization

- Has had a serious nonhealing wound, ulcer, or bone fracture within 4 weeks prior to
randomization

- Has known HIV or AIDS infection

- Has an elective or planned major surgery to be performed during the course of the
trial

- Patient is pregnant or lactating