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

NCT01828021

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: CP-MGAH22-02
  • NCT ID: NCT01828021

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
MargetuximabMGAH22margetuximab

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
margetuximabExperimentalMonotherapy of Anti-HER2 monoclonal antibody

    Eligibility Criteria

            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
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Response
    Time Frame:Cycle 2, Day 21
    Safety Issue:
    Description: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

    Measure:Response Rate
    Time Frame:Following Cycle 2 Day 21 of first 21 patients and following Cycle 2 Day 21 of all 41 patients
    Safety Issue:
    Description: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.
    Measure:Duration of Response
    Time Frame:From day of initial response until the date of first documented progression or death, assessed up to 100 months
    Safety Issue:
    Description: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.
    Measure: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
    Safety Issue:
    Description: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.
    Measure:Overall Survival
    Time Frame:Study Day 1 to date of death from any cause assessed up to 100 months
    Safety Issue:
    Description: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.
    Measure:Safety
    Time Frame:Time of consent to 28 days after last MGAH22 administration
    Safety Issue:
    Description:Adverse events (AEs), serious adverse events (SAEs), Electrocardiogram (ECG) monitoring, monitoring for development of anti-drug antibodies

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Completed
    Lead Sponsor:MacroGenics

    Trial Keywords

    • HER2 2+
    • FISH non-amplified
    • Relapsed
    • Refractory
    • Advanced
    • Margetuximab
    • MGAH22

    Last Updated

    July 25, 2017