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

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