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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

Phase 1
18 Years
Open (Enrolling)
Breast Cancer, Gastric Cancer, Bladder Cancer, Ovarian Cancer, Non-small Cell Lung Cancer

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Trial Information

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

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 by RECIST criteria in patients with measurable
disease or stable measurable or evaluable disease with > 25% decline in relevant tumor
marker) 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.

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 or evaluable disease with relevant tumor marker elevation.

- 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.

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Occurrence of Adverse Events and Serious Adverse Events

Outcome Description:

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.

Outcome Time Frame:

Study Day 50 or 28 days after last infusion

Safety Issue:


Principal Investigator

Stanford J. Stewart, MD

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

July 2010

Completion Date:

June 2013

Related Keywords:

  • Breast Cancer
  • Gastric Cancer
  • Bladder Cancer
  • Ovarian Cancer
  • Non-Small Cell Lung Cancer
  • HER2 positive
  • breast cancer
  • gastric cancer
  • bladder cancer
  • ovarian cancer
  • non-small cell lung cancer
  • Urinary Bladder Neoplasms
  • Breast Neoplasms
  • Carcinoma
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms
  • Stomach Neoplasms
  • Ovarian Neoplasms



Sarah Cannon Research InstituteNashville, Tennessee  37203
National Cancer InstituteBethesda, Maryland  20892-1922