Phase 2 Study of the Monoclonal Antibody MGAH22 (Margetuximab) in Patients With Relapsed or Refractory Advanced Breast Cancer

Inclusion Criteria:

   - Histologically or cytologically confirmed invasive carcinoma of the breast

   - Treatment with 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.
   Patients whose tumors exhibit 2+ staining by IHC are eligible for the study.

   - Patients whose tumors score 1+ by conventional IHC, are non-amplified by FISH testing,
   and whose tumors score > or = 10.5 by HERmark® testing, are eligible for the study.

   - 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 > or = 50%

   - Anti-cancer therapy (including conventional cytotoxic chemotherapy and/or biological
   therapy) and radiotherapy must be completed and any associated toxicities resolved to
      enrollment. Treatment with monoclonal antibodies must be completed at least 14 days
   before entry. Must have completed immunosuppressive medications or vaccinations before
   enrollment.

   - Patients who are estrogen receptor+ and/or progesterone receptor+ and who are
   receiving anti-hormone therapy for at least three months may continue to receive such
   therapy during the course of the trial

   - Eighteen (18) years of age or older

Exclusion Criteria:

   - Major surgery or trauma within 4 weeks

   - Known hypersensitivity to murine or recombinant proteins, polysorbate 80, or any
   excipient contained in the margetuximab 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, at time of study entry, 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
   margetuximab; 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

   - Have previously been exposed to MGAH22 in this or any other trial