This is an open-label, multicenter, dose-escalation study to assess the safety, tolerability, and pharmacokinetics of GDC-0994 in patients with locally advanced or metastatic solid tumors. Patients will be enrolled in one of two stages: a dose-escalation stage (Stage I) or the subsequent expansion stage (Stage II). Stage I will evaluate the safety, tolerability, and pharmacokinetics of increasing doses of GDC-0994 administered daily. Stage II will gather additional data on safety, tolerability, and pharmacokinetics of the recommended dose of GDC-0994 determined in Stage I.

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• 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 RECIST 1.1
• Life expectancy >= 12 weeks
• Adequate hematologic and end organ function
• Consent to provide archival tissue

Exclusion Criteria:

• History of prior significant toxicity from another MEK or ERK inhibitor requiring discontinuation of treatment
• History of parathyroid disorder or history or malignancy-associated hypercalcemia requiring therapy in the past 6 months
• Evidence of visible retinal pathology as assessed by ophthalmologic examination that is considered a risk factor for retinal vein thrombosis or neurosensory retinal detachment
• History of glaucoma
• Intraocular pressure > 21 mmHg as measured by tonometry
• Predisposing factors to retinal vein occlusion, including uncontrolled hypertension, uncontrolled diabetes, uncontrolled hyperlipidemia, and coagulopathy
• History of retinal vein occlusion (RVO), neurosensory retinal detachment, or neovascular macular degeneration
• Allergy or hypersensitivity to components of the GDC-0994 formulation
• 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 or 5 times the half-life whichever is longer
• Current severe, uncontrolled systemic disease
• History of clinically significant cardiac dysfunction
• Pregnancy, lactation, or breastfeeding
• Active autoimmune disease
• Inability or unwillingness to swallow pills
• Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms
• 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 warfarin or thrombolytic anticoagulants
• Uncontrolled ascites requiring weekly large volume paracentesis for 3 consecutive weeks prior to enrollment