An Open-Label, Phase I, Dose-Escalation Study Evaluating the Safety, Tolerability, and Pharmacokinetics 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