A Phase II, Open-Label Study of the Clinical Activity, Safety, and Tolerability of Lapatinib in Combination With Bevacizumab in Subjects With Advanced or Metastatic ErbB2-Overexpressing Breast Cancer

Inclusion Criteria

Inclusion criteria:

- Females that are at least 18 years of age.

- Women of childbearing potential must have a negative serum pregnancy test at
screening.

- Documented evidence of HER2-overexpressing unresectable or metastatic breast cancer.
Disease may/may not have been treated in metastatic setting.

- Subjects are permitted (but not required) to have previously-treated brain metastases
that are stable and asymptomatic.

- Adequate hepatic, renal and cardiac function

- ECOG score 0-1 and a life expectancy of at least 12 weeks.

- Able to swallow oral medication

- Signed informed consent

Exclusion criteria:

- Pregnancy

- Unstable or symptomatic CNS metastases

- Major surgery within 28 days of enrollment (minor surgery within 7 days).

- Prior anti-cancer treatment within 14 days of enrollment, or unresolved
treatment-related toxicities.

- A serious non-healing wound, ulcer, or bone fracture at baseline.

- Class II, III or IV heart failure as defined by the NYHA functional classification
system

- History of significant vascular disease, arterial thrombosis, unstable INR,
hypertensive crisis, or uncontrolled hypertension.

- History of myocardial infarction, stenting procedure, or angioplasty within 6 months
of enrollment.

- History of abdominal fistulae, gastrointestinal perforation, or intra-abdominal
abscess within 6 months of enrollment.

- History of malabsorption syndrome, ulcerative colitis, or bowel obstruction.

- Proteinuria

- Requires concurrent anti-cancer treatment or investigational treatment.

- Known hypersensitivity to either study medication

- Received investigational treatment within 28 days or 5 half-lives, whichever is
longer

- Concurrent disease or circumstances that would lead the investigator would consider
the subject an inappropriate candidate for the study

- Requires medication that has been excluded during study participation