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

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ClinicalTrials.gov Identifier: NCT01828021
Recruitment Status : Completed
First Posted : April 10, 2013
Last Update Posted : August 17, 2018
Sponsor:
Information provided by (Responsible Party):
MacroGenics

Tracking Information
First Submitted Date  ICMJE March 26, 2013
First Posted Date  ICMJE April 10, 2013
Last Update Posted Date August 17, 2018
Actual Study Start Date  ICMJE March 2013
Actual Primary Completion Date December 7, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 25, 2017)
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).
Original Primary Outcome Measures  ICMJE
 (submitted: April 5, 2013)
Response [ Time Frame: Cycle 2, Day 22 ]
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).
Change History Complete list of historical versions of study NCT01828021 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 25, 2017)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: April 5, 2013)
  • Response Rate [ Time Frame: Following Cycle 2 Day 22 of first 21 patients and following Cycle 2 Day 22 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.
  • Duration of Response [ Time Frame: From date of randomization until the date of first documented progression, 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.
  • 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.
  • 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.
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 2 Study of the Monoclonal Antibody MGAH22 (Margetuximab) in Patients With Relapsed or Refractory Advanced Breast Cancer
Official Title  ICMJE 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
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE Biological: Margetuximab
Anti-HER2 monoclonal antibody
Other Name: MGAH22
Study Arms  ICMJE Experimental: margetuximab
Monotherapy of Anti-HER2 monoclonal antibody
Intervention: Biological: Margetuximab
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 Fcγ receptor binding properties. Breast Cancer Res. 2011;13(6):R123. doi: 10.1186/bcr3069. Epub 2011 Nov 30.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 25, 2017)
25
Original Estimated Enrollment  ICMJE
 (submitted: April 5, 2013)
41
Actual Study Completion Date  ICMJE April 14, 2017
Actual Primary Completion Date December 7, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01828021
Other Study ID Numbers  ICMJE CP-MGAH22-02
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party MacroGenics
Study Sponsor  ICMJE MacroGenics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mark D. Pegram, M.D. Stanford University
Study Director: Jan K Davidson-Moncada, M.D. MacroGenics
PRS Account MacroGenics
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP