A Dose-Escalation Study of GDC-0994 in Patients With Locally Advanced or Metastatic Solid Tumors

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