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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01828021
Recruitment Status : Completed
First Posted : April 10, 2013
Last Update Posted : July 9, 2020
Information provided by (Responsible Party):

Brief Summary:
The purpose of this study is to determine if margetuximab is effective in the treatment of certain patients with relapsed or refractory advanced breast cancer.

Condition or disease Intervention/treatment Phase
Breast Cancer Biological: Margetuximab Phase 2

Detailed Description:
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 margetuximab will be justified.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : March 2013
Actual Primary Completion Date : December 7, 2016
Actual Study Completion Date : April 14, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: margetuximab
Monotherapy of Anti-HER2 monoclonal antibody
Biological: Margetuximab
Anti-HER2 monoclonal antibody
Other Name: MGAH22

Primary Outcome Measures :
  1. Response [ Time Frame: Cycle 2, Day 21 ]
    Response based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria based on Cycle 2, Day 21 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 margetuximab. If two or more responses (partial or complete response) are seen at the first tumor re-evaluation on day 21 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).

Secondary Outcome Measures :
  1. Response Rate [ Time Frame: Following Cycle 2 Day 21 of first 21 patients and following Cycle 2 Day 21 of all 41 patients ]
    Response rate is the proportion of patients achieving a best response of complete response or partial response when such responses are confirmed at least 28 days after initial observation of response.

  2. Duration of Response [ Time Frame: From day of initial response until the date of first documented progression or death, assessed up to 100 months ]
    Duration of response is defined as the number of days from initial response to date of disease progression or death. A patient's response duration will be censored if at the time of study completion or study withdrawal, response is ongoing.

  3. Progression-free survival [ Time Frame: Study Day 1 to date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months ]
    Progression-free survival (PFS) is defined as the number of days from the date of study enrollment (Study Day 1) to the date of disease progression, death, study completion or study withdrawal, whichever occurs first. A patient's PFS will be censored if at the time of study completion or study withdrawal, disease progression or death has not occurred.

  4. Overall Survival [ Time Frame: Study Day 1 to date of death from any cause assessed up to 100 months ]
    Overall survival (OS) is defined as the number of days from the date of study enrollment (Study Day 1) to the date of death (by any cause) or last observation, whichever occurs first. A patient's OS will be censored if at the time of study completion or study withdrawal, the patient remains alive.

  5. Safety [ Time Frame: Time of consent to 28 days after last MGAH22 administration ]
    Adverse events (AEs), serious adverse events (SAEs), Electrocardiogram (ECG) monitoring, monitoring for development of anti-drug antibodies

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 </= 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 14 days before entry. Must have completed immunosuppressive medications or vaccinations before enrollment.
  • Patients who are ER+ and/or PR+ 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01828021

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United States, California
University of California San Francisco
San Francisco, California, United States, 94115
Stanford University
Stanford, California, United States, 94305
United States, Florida
Florida Cancer Research Institute
Plantation, Florida, United States, 33324
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Tufts Cancer Center
Boston, Massachusetts, United States, 02111
United States, Tennessee
Tennessee Oncology
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
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Principal Investigator: Mark D. Pegram, M.D. Stanford University
Study Director: Edwin Rock, MD MacroGenics
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Responsible Party: MacroGenics Identifier: NCT01828021    
Other Study ID Numbers: CP-MGAH22-02
First Posted: April 10, 2013    Key Record Dates
Last Update Posted: July 9, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by MacroGenics:
HER2 2+
FISH non-amplified
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases