A Study of Ramucirumab (IMC-1121B) in Combination With Eribulin Versus Eribulin Alone in Patients With Breast Cancer

Inclusion Criteria:

- Have histologically or cytologically confirmed invasive breast cancer which at the
time of study entry is either locally-recurrent disease not amenable to curative
therapy or Stage IV disease (American Joint Committee on Cancer Staging Criteria for
breast cancer)

- Have measurable and/or nonmeasurable disease per Response Evaluation Criteria in
Solid Tumors (RECIST 1.1)

- Have received at least 2 but not more than 4 prior cytotoxic chemotherapy regimens in
the locally recurrent or metastatic setting

- Have received prior treatment with both anthracyclines and taxanes, either in the
metastatic, adjuvant or neoadjuvant setting

- Have received HER-2-directed treatment; or are not a candidate for HER-2-directed
treatment if the patient has HER-2 positive disease

- Have completed any prior radiotherapy and/or hormonal therapy at least 1 week prior
to randomization and have recovered from all clinically significant treatment-related
toxicities

- Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

- Have left ventricular ejection fraction within normal limits

- Have discontinued all previous chemotherapy treatments for cancer at least 3 weeks
prior to randomization and recovered from clinically significant toxic effects

- Have resolution to Grade less than or equal to 1 [by the National Cancer Institute -
Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0] of all
clinically significant toxicities of prior chemotherapy, surgery, radiotherapy, or
hormonal therapy with the exception of peripheral neuropathy, which must have
resolved to Grade less than or equal to 2

- Have adequate hematologic, hepatic, renal, and coagulation function

- Test negative for pregnancy

- Have a life expectancy of at least 3 months

Exclusion Criteria:

- Have a concurrent active other malignancy other than adequately treated
non-melanomatous skin cancer or other noninvasive or in situ neoplasms

- Are currently enrolled in, or recently discontinued from, a clinical trial involving
an investigational product, or concurrently enrolled in any other type of medical
research judged not to be medically compatible with the study

- Have received investigational therapy within 3 weeks prior to randomization

- Have received prior ramucirumab or eribulin

- Have a known sensitivity to agents of similar biologic composition as ramucirumab,
halichondrin B and/or halichondrin B chemical derivative

- Have received bevacizumab within 6 weeks prior to randomization

- Have uncontrolled or poorly controlled hypertension

- Have congenital prolonged QTc syndrome (or have a family history)or prolongation of
QTc at baseline

- Have a history of additional risk factors for Torsades des pointes within the last
year prior to randomization

- Have an implantable pacemaker or automatic implantable cardioverter defibrillator

- Have bradycardia

- Have an acute/subacute bowel obstruction or history of chronic diarrhea requiring
ongoing medical intervention within 6 months prior to randomization

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

- Have experienced a Grade 3 or greater bleeding event within 3 months prior to
randomization

- Have experienced any Grade 3 or greater arterial thromboembolic events within 6
months prior to randomization, or venous thromboembolic event within 3 months prior
to randomization

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

- Have a planned major surgery to be performed during the course of the trial

- Have uncontrolled metabolic conditions

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

- Have known human immunodeficiency virus (HIV) infection or acquired immunodeficiency
syndrome (AIDS)

- Have pulmonary lymphangitic involvement that results in pulmonary dysfunction
requiring active treatment including the use of oxygen

- Have received a prior allogeneic organ or tissue transplantation

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

- Have known leptomeningeal metastases

- Have cirrhosis (Child-Pugh Level B or worse) or cirrhosis (any degree) and a history
of hepatic encephalopathy or clinically meaningful ascites