A Single Arm, Open-Label, Phase 2 Study of MGAH22 (Fc-optimized Chimeric Anti-HER2 Monoclonal Antibody) in Patients With Relapsed or Refractory Advanced Breast Cancer Whose Tumors Express HER2 at the 2+ Level by Immunohistochemistry and Lack Evidence of HER2 Gene Amplification by FISH

Inclusion Criteria:

- Histologically or cytologically confirmed invasive carcinoma of the breast

- Evidence of progression of disease during or following at least two prior systemic
therapies for advanced (unresectable locoregional or metastatic) disease

- Evidence of HER2 oncoprotein expression at the 2+ level by central laboratory

- Evidence of lack of HER2 oncogene amplification as determined by FISH testing by
central laboratory

- Performance Status of 0 or 1

- Life expectancy at least 6 months

- Measurable disease (by RECIST 1.1)

- Acceptable laboratory parameters and organ reserve

- Baseline left ventricular ejection fraction >50%

- Anti-cancer therapy must be completed and any associated toxicities resolved to
<=Grade 1 levels or baseline levels and at least 2 weeks must have elapsed before
enrollment. Treatment with monoclonal antibodies must be completed at least 28 days
before entry. Must have completed immunosuppressive medications or vaccinations
before enrollment

Exclusion Criteria:

- Major surgery or trauma within 4 weeks

- Known hypersensitivity to murine or recombinant proteins, polysorbate 80, or any
excipient contained in the MGAH22 drug formulation

- Second primary malignancy that has not been in remission for more than 3 years

- History of active viral, bacterial, or systemic fungal infection requiring parenteral
treatment within 14 days

- History within 3 months of deep vein thrombosis, pulmonary embolism, or stroke

- Symptomatic or untreated central nervous system (CNS) metastatic disease Patients
with previously treated CNS metastatic disease which has been stable for at least 56
days are eligible

- Requirement for concurrent steroids > 10 mg/day of oral prednisone or the equivalent,
except steroid inhaler, nasal spray, or ophthalmic solution

- Serious medical condition that would impair the ability to receive or tolerate
MGAH22; dementia or altered mental status that would preclude provision of informed
consent

- Uncontrolled hypertension, heart disease including history of congestive heart
failure, history of myocardial infarction, angina pectoris requiring medication,
clinically significant valvular heart disease, high risk arrhythmias, or disease
corresponding to New York Heart Association class III or IV.

- Significant pulmonary compromise