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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

Phase 2
18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

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

In the pivotal study that established that Herceptin® was highly effective when added to
standard chemotherapy in the front-line treatment of women with HER2 positive metastatic
breast cancer, benefit appeared to accrue to those patients whose tumors expressed the HER2
oncoprotein at the 3+ level by immunohistochemistry (IHC) or those patients whose tumors
demonstrated evidence of HER2 gene amplification by fluorescence in situ hybridization
(FISH) testing. Similarly, when Herceptin® was used as a single therapy in women with
metastatic breast cancer that had progressed following cytotoxic chemotherapy, 3+
overexpression of HER2, but not 2+ expression, was associated with response to treatment.
These and other studies have led to the recommendation that Herceptin® should be
administered to patients with breast cancer whose tumors exhibit 3+ overexpression or gene
amplification. This study will evaluate whether treatment of patients with tumors that would
not be expected to respond to Herceptin® therapy, namely those that lack HER2 gene
amplification and express the oncoprotein at the 2+ level by IHC, may benefit from the use
of the anti-HER2 monoclonal antibody, MGAH22. If 5 or more responses are seen in 41
evaluable patients, then further clinical development of MGAH22 will be justified.

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

- 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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:


Outcome Description:

Response based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria based on Cycle 2, Day 22 computed tomography (CT) scans. This study will employ a Simon two-stage optimum design in which an initial cohort of 21 patients will be treated with MGAH22. If two or more responses (partial or complete response) are seen at the first tumor re-evaluation on day 22 of Cycle 2, the study will be expanded to include up to 41 patients (20 additional patients in Cohort 2, the second stage of the study) in order to determine whether further development of the drug is warranted (5 or more responses in 41 evaluable patients).

Outcome Time Frame:

Cycle 2, Day 22

Safety Issue:


Principal Investigator

Mark D. Pegram, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Stanford University


United States: Food and Drug Administration

Study ID:




Start Date:

March 2013

Completion Date:

August 2014

Related Keywords:

  • Breast Cancer
  • HER2 2+
  • FISH non-amplified
  • Relapsed
  • Refractory
  • Advanced
  • Margetuximab
  • Breast Neoplasms



Stanford University Stanford, California  94305
University of California San Francisco San Francisco, California  941104206
Indiana University Indianapolis, Indiana  46202
Tennessee Oncology Nashville, Tennessee  37203
Florida Cancer Research Institute Davie, Florida  
Tufts Cancer Center Boston, Massachusetts  02111