Study of the Safety and Pharmacology of GDC-0980 in Combination With Paclitaxel With or Without Bevacizumab in Patients With Locally Recurrent or Metastatic Breast Cancer

A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacology of GDC-0980 in Combination With Paclitaxel With or Without Bevacizumab in Patients With Locally Recurrent or Metastatic Breast Cancer

This is an open-label, multicenter, Phase Ib dose-escalation study to assess the safety, tolerability, and pharmacokinetics of GDC-0980 administered with taxane-based chemotherapy regimens utilized in patients with locally recurrent or metastatic breast cancer.

Inclusion Criteria:

• Locally recurrent or metastatic breast cancer, not amenable to resection with curative intent
• For Arm C: Overexpression of HER2
• Eastern Cooperative Oncology Group Performance Status of 0 or 1
• Adequate hematologic and organ function
• Evaluable or measurable disease per RECIST (Response Evaluable Criteria in Solid Tumors)
• Female patients of childbearing potential must use an acceptable method of contraception to prevent pregnancy and to continue its use for the duration of the study

Exclusion Criteria:

• Prior anti-cancer therapy of more than two regimens of systemic cytotoxic chemotherapy for advanced or metastatic breast cancer
• Prior anti-cancer therapy (e.g., chemotherapy, biologic therapy, or hormonal therapy) within a specified timeframe of the first dose of study treatment
• History of Type 1 or Type 2 diabetes requiring regular medication
• History of clinically significant cardiac or pulmonary dysfunction
• History of malabsorption syndrome or other condition that would interfere with enteral absorption
• Any condition requiring full-dose anticoagulants
• Leptomeningeal disease as a manifestation of cancer
• Active infection requiring IV antibiotics
• Active autoimmune disease that is not controlled by non-steroidal anti-inflammatory drugs, inhaled steroids, or the equivalent of <= 10 mg/day of prednisone
• Known clinically significant history of liver disease, including active viral, alcoholic, or other hepatitis, or cirrhosis
• Known HIV infection
• Known untreated or active CNS metastases
• Pregnancy, lactation, or breastfeeding
• Major surgical procedure, open biopsy, or significant traumatic injury within a within a specified timeframe of the first dose of study treatment

For Arm B:

• Uncontrolled hypertension, complication from hypertension, myocardial infarctions, unstable angina, vascular disease or stroke within a specified timeframe of the first dose of study treatment
• Evidence of bleeding diathesis or significant coagulopathy including hemoptysis within a specified timeframe of the first dose of study treatment
• History of abdominal conditions (e.g., fistula, perforation, obstruction) that would preclude use of bevacizumab
• Serious, non-healing wound, active ulcer, or untreated bone fracture
• Proteinuria