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.
- 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%
- 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.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both