A Study of the Efficacy and Safety of Trastuzumab-MCC-DM1 vs. Trastuzumab (Herceptin®) and Docetaxel (Taxotere®) in Patients With Metastatic HER2-Positive Breast Cancer Who Have Not Received Prior Chemotherapy for Metastatic Disease

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the breast with locally advanced or metastatic disease, and a candidate for chemotherapy
• HER2-positive
• No prior chemotherapy for their MBC
• Measurable disease
• Age ≥ 18 years
• For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective, non-hormonal form of contraception or two effective forms of non-hormonal contraception by the patient and/or partner. Contraception use must continue for the duration of study treatment and for at least 6 months after the last dose of study treatment. Male patients whose partners are pregnant should use condoms for the duration of the study.

Exclusion Criteria:

• History of any chemotherapy for MBC
• An interval of < 6 months from the completion of cytotoxic chemotherapy in the neo-adjuvant or adjuvant setting until the time of metastatic diagnosis
• Trastuzumab ≤ 21 days prior to randomization
• Hormone therapy < 7 days prior to randomization
• Current peripheral neuropathy of Grade ≥ 3
• History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other cancers with a similar outcome as those previously mentioned
• Previous radiotherapy for the treatment of unresectable, locally advanced or metastatic breast cancer is not allowed if: more than 25% of marrow-bearing bone has been irradiated; the last fraction of radiotherapy has been administered within approximately 3 weeks prior to randomization.
• Brain metastases that are untreated, symptomatic, or require therapy to control symptoms; or any radiation, surgery, or other therapy to control symptoms from brain metastases within 2 months prior to randomization
• History of exposure to the following cumulative doses of anthracyclines: Doxorubicin or liposomal doxorubicin > 500 mg/m^2; Epirubicin > 900 mg/m^2; Mitoxantrone > 120mg/m^2 and idarubicin > 90 mg/m^2
• Current unstable angina
• History of symptomatic congestive heart failure, or ventricular arrhythmia requiring treatment
• History of myocardial infarction within 6 months prior to randomization
• LVEF below 50% within approximately 28 days prior to randomization
• History of decreased LVEF or symptomatic CHF with previous adjuvant trastuzumab treatment
• Cardiac troponin I ≥ 0.2 ng/mL within 28 days of randomization
• Severe dyspnea at rest because of complications of advanced malignancy or requiring current continuous oxygen therapy
• Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures)
• Major surgical procedure or significant traumatic injury within approximately 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment
• Current pregnancy or lactation
• History of receiving any investigational treatment within approximately 28 days prior to randomization
• Current known infection with HIV, active hepatitis B and/or hepatitis C virus
• History of intolerance (including Grade 3-4 infusion reaction) or hypersensitivity to trastuzumab, murine proteins, or docetaxel
• Known hypersensitivity to any of the study drugs, including the excipients, or any drugs formulated in polysorbate 80
• Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol