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