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