A Study Evaluating the Safety, Tolerability and Pharmacokinetics of GDC-0973 in Combination With GDC-0941 When Administered in Patients With Locally Advanced or Metastatic Solid Tumors

• Incidence and nature of dose-limiting toxicities [ Time Frame: Through study completion or early study discontinuation ] [ Designated as safety issue: No ]
• Incidence, nature and severity of adverse events and serious adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0 [ Time Frame: Through study completion or early study discontinuation ] [ Designated as safety issue: No ]
• PK parameters of GDC-0941 and GDC-0973 (total exposure, maximum plasma\n\nconcentration, and minimum concentration) [ Time Frame: Through study completion or early study discontinuation ] [ Designated as safety issue: No ]

• Objective response [ Time Frame: Through study completion or early study discontinuation ] [ Designated as safety issue: No ]
• Duration of objective response [ Time Frame: Through study completion or early study discontinuation ] [ Designated as safety issue: No ]
• Progression-free survival (PFS) for patients with measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) [ Time Frame: Through study completion or early study discontinuation ] [ Designated as safety issue: No ]

This is an open-label, multicenter, Phase Ib dose-escalation study designed to assess the safety, tolerability and pharmacokinetics of oral dosing of GDC-0973 and GDC-0941 administered in combination in patients with solid tumors.

• Drug: GDC-0941
  Repeating oral dose
• Drug: GDC-0973/XL518
  Repeating oral dose

Inclusion Criteria:

• Histologically or cytologically documented, locally advanced or metastatic solid tumors for which standard therapy either does not exist or has proven ineffective or intolerable
• Evaluable disease or disease measurable per Response Evaluation Criteria in Solid Tumors (RECIST)
• Life expectancy >= 12 weeks
• Adequate hematologic and end organ function
• Agreement to use an effective form of contraception for the duration of the study

Exclusion Criteria:

• History of prior significant toxicity from another MEK pathway inhibitor requiring discontinuation of treatment
• History of prior significant toxicity from another PI3K pathway inhibitor requiring discontinuation of treatment
• Allergy or hypersensitivity to components of the GDC-0973 or GDC-0941 formulations
• Palliative radiotherapy within 2 weeks prior to first dose of study drug treatment in Cycle 1
• Experimental therapy within 4 weeks prior to first dose of study drug treatment in Cycle 1
• Major surgical procedure or significant traumatic injury within 4 weeks prior to first dose of study drug treatment in Cycle 1, or anticipation of the need for major surgery during the course of study treatment
• Prior anti-cancer therapy within 28 days before the first dose of study drug treatment in Cycle 1
• History of diabetes requiring daily medication, or history of Grade >= 3 fasting hyperglycemia
• Current severe, uncontrolled systemic disease
• History of clinically significant cardiac or pulmonary dysfunction
• History of malabsorption 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 thrombolytics
• Active autoimmune disease
• Uncontrolled ascites requiring weekly large volume paracentesis for 3 consecutive weeks prior to enrollment
• Pregnancy, lactation, or breastfeeding
• Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms
• No other history of or ongoing malignancy that would potentially interfere with the interpretation of the pharmacodynamic or efficacy assays