A Phase I, Open Label, Parallel Group, Pharmacokinetic Study of Trastuzumab Emtansine in Patients With HER2-Positive Metastatic Breast Cancer and Normal or Reduced Hepatic Function

Inclusion Criteria:

- Adult patients, >/= 18 years of age

- Histologically or cytologically documented invasive metastatic breast cancer

- Human epidermal growth factor receptor 2 (HER2) -positive disease

- Adequate bone marrow and organ function (other than hepatic dysfunction allowed by
protocol)

- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

- Left ventricular ejection fraction >/=50%

- Normal hepatic function, or mild to moderate hepatic impairment (Child-Pugh Class A
or B)

Exclusion Criteria:

- History of Grade >/=3 infusion reaction, hypersensitivity reaction, or pneumonitis in
response to trastuzumab

- Investigational therapy or any other anticancer therapy treatment

- Previous treatment with trastuzumab emtansine

- Brain metastases that are untreated or symptomatic or require therapy to control
symptoms or any radiation, surgery or other therapy to control symptoms from brain
metastases within 1 month of the first study treatment

- 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 mentioned above

- Current peripheral neuropathy of Grade >/=2

- Child-Pugh Class C hepatic impairment

- Encephalopathy >/= Grade 2

- For patients with normal hepatic function: history of drug or alcohol addiction or
history of hepatitis B and/or hepatitis C

- Active hepatitis A, B and/or C

- Current unstable ventricular arrhythmia requiring treatment

- History of symptomatic CHF (NYHA Classes II-IV)

- History of myocardial infarction or unstable angina within 6 months of enrollment

- History of a decrease in LVEF to<40% or symptomatic CHF with previous trastuzumab
treatment

- Pregnant or lactating women

- Known HIV infection