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Safety Study of MGAH22 in HER2-positive Carcinomas

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: NCT01148849
Recruitment Status : Active, not recruiting
First Posted : June 22, 2010
Last Update Posted : February 24, 2021
Green Cross Corporation
National Cancer Institute (NCI)
Information provided by (Responsible Party):

Brief Summary:
The purpose of this study is to determine if MGAH22 is safe when given by intravenous (IV) infusion to patients with HER2-positive cancer. The study will also evaluate how long MGAH22 stays in the blood and how long it takes for it to leave the body, what is the highest dose that can safely be given, and whether it has an effect on tumors.

Condition or disease Intervention/treatment Phase
Breast Cancer Gastric Cancer Biological: MGAH22 Phase 1

Detailed Description:

An open-label, multi-dose, single-arm, multi-center, Phase 1, dose-escalation study will be conducted to define the toxicity profile, MTD, PK, immunogenicity, and potential antitumor activity of MGAH22 in patients with refractory HER2 positive breast cancer and patients with other carcinomas that overexpress HER2 for whom no standard therapy is available. After an MTD has been defined, an additional cohort of patients will be treated at the MTD to obtain further information regarding the safety of the chosen dose, to definitively describe PK, and to evaluate potential anti-tumor activity of MGAH22.

Patients will be monitored for a minimum of four weeks after administration of the final dose of MGAH22. The National Cancer Institute's (NCI's) Common Terminology Criteria for Adverse Events (CTCAE), v.4.0, will be used for grading AEs except as noted within the protocol. Study assessments will include AE monitoring, ECG monitoring, PK analysis of serum MGAH22, determination of the serum concentration of soluble MGAH22 and tumor markers, and an assessment of potential anti-MGAH22 antibody [human anti-chimeric antibody (HACA)] response.

Tumor response assessments using Study Day 43 CT scans will be performed approximately six weeks after the first MGAH22 dose for each patient. Patients with evidence of disease regression (partial or complete response or stable disease by RECIST criteria) will be allowed to continue therapy at the same dose, or at a reduced dose if warranted by DLT or significant AE in Cycle 1. Subsequent cycles which will begin on Study Day 50 will consist of MGAH22 administration on Study Days 1, 8, and 15 of each 28-day cycle, with tumor evaluation every other cycle. Responding patients may receive continued antibody therapy until evidence of progression of disease is documented or the patient experiences DLT. Patients who have responded and received at least 3 years of MGAH22 study therapy may continue MGAH22 post-progression, with or without chemotherapy, at the Investigators' discretion.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 66 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Dose Escalation Study of MGAH22 in Patients With Refractory HER2 Positive Breast Cancer and Patients With Other HER2 Positive Carcinomas for Whom No Standard Therapy Is Available
Study Start Date : July 2010
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: MGAH22
Anti-HER2 monoclonal antibody (margetuximab)
Biological: MGAH22

MGAH22 will be administered by IV infusion once per week for 4 weeks in the following dose escalation cohorts: 0.1, 0.3, 1.0, 3.0, and 6.0 mg/kg; and once every 3 weeks in the following dose escalation cohorts: 10.0, 15.0, and 18.0 mg/kg.

An additional cohort of up to 24 patients with breast or gastric cancer will be enrolled and treated at a dose of 15 mg/kg every three weeks.

Primary Outcome Measures :
  1. Occurrence of Adverse Events and Serious Adverse Events [ Time Frame: Study Day 50 or 28 days after last infusion ]
    Note that serious adverse events that are considered study drug related can be reported at any time after Study Day 50 or 28 days after the last infusion.

Secondary Outcome Measures :
  1. Maximum tolerated dose [ Time Frame: Study day 50 or 28 days after last infusion ]

Information from the National Library of Medicine

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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 carcinoma that overexpresses HER2 by immunohistochemistry (2+ or 3+ positivity by HercepTest or equivalent).
  • Progressive disease during or after last treatment regimen.
  • Appropriate treatment history for histological entity.
  • ECOG Performance Status <= 1.
  • Life expectancy >= 3 month.
  • Measurable disease
  • Acceptable laboratory parameters and adequate organ reserve.
  • Baseline LVEF >50%

Exclusion Criteria:

  • Lifetime anthracycline exposure > 350 mg/m2 of doxorubicin or equivalent
  • Major surgery within four weeks before enrollment.
  • Known hypersensitivity to murine or recombinant proteins, polysorbate 80, or any excipient contained in the drug formulation.
  • Second primary malignancy that has not been in remission for greater than 3 years. Treated non-melanoma skin cancer, cervical carcinoma in situ on biopsy, or squamous intraepithelial lesion on PAP smear, localized prostate cancer (Gleason score < 6), or resected melanoma in situ are exceptions and do not require a 3 year remission.
  • Active viral, bacterial, or systemic fungal infection requiring parenteral treatment within four weeks of enrollment. Patients requiring any oral antiviral, fungal, or bacterial therapy must have completed treatment within one week of enrollment.
  • History of chronic or recurrent infections that require continual use of antiviral, antifungal, or antibacterial agents.
  • History of deep vein thrombosis, pulmonary embolism, myocardial infarction, or stroke within three months of enrollment.
  • Known history of central nervous system (CNS) metastatic disease with evidence of residual or recurrent disease upon entry.
  • New York Heart Association class III or IV heart disease.

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): NCT01148849

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United States, Maryland
National Cancer Institute
Bethesda, Maryland, United States, 20892
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of, 110-744
Sponsors and Collaborators
Green Cross Corporation
National Cancer Institute (NCI)
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Study Director: Fernanda Arnaldez, MD MacroGenics
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: MacroGenics Identifier: NCT01148849    
Obsolete Identifiers: NCT01195935
Other Study ID Numbers: CP-MGAH22-01
02598-10 ( Other Grant/Funding Number: NCI CRADA )
First Posted: June 22, 2010    Key Record Dates
Last Update Posted: February 24, 2021
Last Verified: February 2021
Keywords provided by MacroGenics:
HER2 positive
breast cancer
gastric cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Stomach Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Antineoplastic Agents