A Phase Ib, Open-Label Study of the Safety, Tolerability, Pharmacokinetics, and Activity of Trastuzumab and Trastuzumab-MCC-DM1 Administered Intravenously and GDC-0941 Administered Orally to Patients With HER2-Positive Metastatic Breast Cancer Who Have Progressed on Previous Trastuzumab-Based Therapy

Inclusion Criteria:

- Histologically documented locally advanced or metastatic breast cancer that has
progressed on at least one trastuzumab-based regimen in the metastatic or locally
advanced setting

- HER2-positive disease documented by one of the following results using FDA-approved
testing methods: FISH-positive, chromogenic in situ hybridization (CISH)-positive,
or IHC 3 + by local laboratory assessment

- Life expectancy >= 90 days

- Agreement to use an effective form of contraception for the duration of the study

Exclusion Criteria:

- History of Grade >= 3 hypersensitivity reaction to trastuzumab, or Grade >= 1 with
the most recent trastuzumab infusion before study entry, or continued requirement for
prolonged trastuzumab infusions to prevent hypersensitivity reactions

- History of intolerance to trastuzumab and/or adverse events related to trastuzumab
that resulted in trastuzumab being permanently discontinued

- Prior anti-cancer therapy (e.g., biologic or other targeted therapy, chemotherapy,
hormonal therapy) within 2 weeks prior to Day 1

- Prior investigational anti-cancer therapy within 4 weeks prior to Day 1

- Grade >= 2 peripheral neuropathy

- History of Grade >= 3 hyperglycemia (fasting)

- History of Type 1 or Type 2 diabetes requiring daily medication

- History of clinically significant cardiac or pulmonary dysfunction

- History of malabsorption syndrome or other condition that would interfere with
enteral absorption

- Clinically significant history of liver disease, including cirrhosis, current alcohol
abuse, or current known active infection with HIV, hepatitis B virus, or hepatitis C
virus

- Any condition requiring anticoagulants, such as warfarin, heparin, or thrombolytic
agents

- Any condition requiring > 2 grams of acetaminophen daily

- Need for current chronic corticosteroid therapy

- Pregnancy, lactation, or breast-feeding

- Current severe, uncontrolled systemic disease (e.g., clinically significant
cardiovascular, pulmonary, or metabolic disease)

- Major surgical procedure or significant traumatic injury within 28 days prior to Day
1, or anticipation of the need for major surgery during the course of study treatment

- Symptomatic hypercalcemia requiring continued use of bisphosphonate therapy

- Known brain metastases that are untreated, symptomatic, or require therapy to control
symptoms