Breast CancerPhase 2NCT01828021
Phase 2 Study of the Monoclonal Antibody MGAH22 (Margetuximab) in Patients With Relapsed or Refractory Advanced Breast Cancer
A Phase 2 study testing Margetuximab in people with Breast Cancer, run by MacroGenics at 6 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Margetuximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 6 sitesUnited States
- Study dates
- Mar 2013to 14 Apr 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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 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
Who cannot join
- 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
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- 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
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Tufts Cancer Center
Boston, Massachusetts, 02111
Indiana University
Indianapolis, Indiana, 46202
Tennessee Oncology
Nashville, Tennessee, 37203
Florida Cancer Research Institute
Plantation, Florida, 33324
University of California San Francisco
San Francisco, California, 94115
Stanford University
Stanford, California, 94305
About this study
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
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.
Read the 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.
- Conditions
- Breast Cancer
- Being tested
- Margetuximab
- Keywords
- HER2 2+, FISH non-amplified, Relapsed, Refractory, Advanced, Margetuximab, MGAH22
- Medical subject headings
- Breast Neoplasms, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MargetuximabBiological
Also called MGAH22
Anti-HER2 monoclonal antibody
| Study group | Role | What they receive |
|---|---|---|
| margetuximab | Experimental | Monotherapy of Anti-HER2 monoclonal antibody Receives: Biological: Margetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best Overall Response
Response based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria based on Cycle 2, Day 21 computed tomography (CT) scans. Response is categorized as complete response (CR): disappearance of all target lesions, confirmed at ≥ 4 weeks; partial response (PR): ≥ 30% decrease in target lesions from baseline, confirmed at ≥ 4 weeks; progressive disease (PD): ≥ 20% increase over smallest sum observed with an absolute increase of at least 5 mm, or appearance of new lesions; and stable disease (SD): neither PR or PD criteria met.
A Simon two-stage design was planned in which an initial cohort of 21 patients was treated. If 2 or more responses (PR or CR) are seen at the first tumor re-evaluation on day 21 of Cycle 2, the study would 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).
Measured: Cycle 2, Day 21
Secondary outcomes (1)
Response Rate
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.
Response based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria based on Cycle 2, Day 21 computed tomography (CT) scans. Response is categorized as complete response (CR): disappearance of all target lesions, confirmed at ≥ 4 weeks; partial response (PR): ≥ 30% decrease in target lesions from baseline, confirmed at ≥ 4 weeks; progressive disease (PD): ≥ 20% increase over smallest sum observed with an absolute increase of at least 5 mm, or appearance of new lesions; and stable disease (SD): neither PR or PD criteria met.
Measured: Day 49
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2013 (estimated)
- Study startMar 2013
- Primary completion7 Dec 2016
- Study completion14 Apr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- MacroGenics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01828021
- Sponsor's protocol ID
- CP-MGAH22-02
- Status last verified
- Feb 2025
- First submitted
- 26 Mar 2013
- Last updated
- 13 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Nordstrom JL, Gorlatov S, Zhang W, Yang Y, Huang L, Burke S, Li H, Ciccarone V, Zhang T, Stavenhagen J, Koenig S, Stewart SJ, Moore PA, Johnson S, Bonvini E. Anti-tumor activity and toxicokinetics analysis of MGAH22, an anti-HER2 monoclonal antibody with enhanced Fcgamma receptor binding properties. Breast Cancer Res. 2011;13(6):R123. doi: 10.1186/bcr3069. Epub 2011 Nov 30.
PubMed 22129105
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01828021
- Acronym / sponsor ID
- CP-MGAH22-02
- Conditions
- Breast Cancer
- Keywords
- HER2 2+, FISH non-amplified, Relapsed, Refractory, Advanced, Margetuximab, MGAH22
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- MacroGenicsIndustry (pharma, biotech, devices)
- Study start
- Mar 2013 (actual)
- Primary completion
- 7 Dec 2016 (actual)
- Study completion
- 14 Apr 2017 (actual)
- First posted
- 10 Apr 2013 (estimated)
- Results
- Posted 17 Sep 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| margetuximab | Experimental | Biological: MargetuximabMonotherapy of Anti-HER2 monoclonal antibody |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MargetuximabAlso: MGAH22Anti-HER2 monoclonal antibody | Biological | margetuximab |
Primary outcome
Best Overall 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. Response is categorized as complete response (CR): disappearance of all target lesions, confirmed at ≥ 4 weeks; partial response (PR): ≥ 30% decrease in target lesions from baseline, confirmed at ≥ 4 weeks; progressive disease (PD): ≥ 20% increase over smallest sum observed with an absolute increase of at least 5 mm, or appearance of new lesions; and stable disease (SD): neither PR or PD criteria met. A Simon two-stage design was planned in which an initial cohort of 21 patients was treated. If 2 or more responses (PR or CR) are seen at the first tumor re-evaluation on day 21 of Cycle 2, the study would 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).
1 secondary outcome
Response Rate
Time frame: Day 49
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22129105Nordstrom JL, Gorlatov S, Zhang W, Yang Y, Huang L, Burke S, Li H, Ciccarone V, Zhang T, Stavenhagen J, Koenig S, Stewart SJ, Moore PA, Johnson S, Bonvini E. Anti-tumor activity and toxicokinetics analysis of MGAH22, an anti-HER2 monoclonal antibody with enhanced Fcgamma receptor binding properties. Breast Cancer Res. 2011;13(6):R123. doi: 10.1186/bcr3069. Epub 2011 Nov 30.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Margetuximab in people with Breast Cancer, run by MacroGenics at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Best Overall Response (time frame: Cycle 2, Day 21). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01828021, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2025.