A Study of the Safety, Tolerability, and Effects of Cobimetinib and 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
* Life expectancy \> or = 12 weeks
* Adequate hematologic and end organ function
* For female patients of childbearing potential and male patients with partners of childbearing potential, use of an effective form of contraception with continued use for study duration and up to 3 months or more following discontinuation of treatment drug
* Fluorodeoxyglucose positron emission tomography (FDG-PET) avid disease on baseline scan

For enrollment in part 2, patients must meet all of the following:

* Measurable disease
* No more than four prior systemic therapies for locally advanced or metastatic cancer

Exclusion Criteria:

* History of prior significant toxicity from another MEK inhibitor or ERK inhibitor requiring discontinuation of treatment
* Evidence of visible retinal pathology as assessed by ophthalmologic examination that is considered a risk factor for retinal vein thrombosis
* History of glaucoma
* Intraocular pressure \> 21 mmHg as measured by tonometry
* Predisposing factors to retinal vein occlusion (RVO)
* History of RVO, neurosensory retinal detachment, or neovascular macular degeneration
* Allergy or hypersensitivity to components of the cobimetinib or 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 the first dose of study-drug treatment in Cycle 1, or anticipation of the need for major surgery during the course of study treatment
* Anti-cancer therapy within 28 days prior to the first dose of study-drug treatment in Cycle 1
* Current severe, uncontrolled systemic disease
* History of clinically significant cardiac dysfunction
* History of symptomatic congestive heart failure or serious cardiac arrhythmia requiring treatment
* History of myocardial infarction within 6 months prior to the first dose of study-drug treatment in Cycle 1
* History of congenital long QT syndrome or QTc \> 470 msec
* LVEF
* History of malabsorption or other condition that would interfere with enteral absorption
* Clinically significant history of liver disease, current alcohol abuse, or current known active infection with HIV, hepatitis B virus, or hepatitis C virus
* Any condition requiring warfarin or thrombolytic anticoagulants
* 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 (PD) or efficacy assays