Inclusion Criteria:

• 18 years of age or older
• Histologically confirmed metastatic or unresectable solid tumor
• Glutamic acid-for-valine substitution at amino acid position 600 in the BRAF gene or other activating BRAF mutation, as determined by high-throughput genotyping
• Patients may have received any number of prior systemic treatments for their cancer
• At least one measurable site of disease by CT, according to standard RECIST criteria
• ECOG Performance Status 0-1
• Estimated life expectancy > 12 weeks
• Absolute neutrophil count > 1500 per cubic mm
• Platelet Count > 100,000 per cubic mm
• Hemoglobin > 9 g/dl
• Serum bilirubin < 1.5 x upper limit of normal
• Serum AST and ALT < 2.5 x upper limit of normal
• Serum Creatinine < 1.5 x upper limit of normal
• For women of childbearing potential, negative serum pregnancy test and use of physician-approved method of birth control throughout the study

Exclusion Criteria:

• Patients with melanoma
• Have received chemotherapy or radiotherapy within 4 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin C), or a targeted therapy within 2 weeks prior to entering the study
• Have not recovered from adverse events due to agents previously administered (CTCAE v. 3.0 grade 1 or baseline)
• Currently receiving other investigational agents
• Known brain metastases, unless treated and stable off of corticosteroids for at least four weeks
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD6244
• Prior treatment with a selective inhibitor of RAF or MEK (Prior sorafenib is allowed)
• Uncontrolled intercurrent illness, including but not limited to, clinically significant active infection; symptomatic congestive heart failure, unstable angina pectoris, and/or cardiac arrhythmia other than atrial fibrillation; psychiatric illness/social situations that would limit compliance with study requirements
• Refractory nausea or vomiting, swallowing disorder, or malabsorption syndrome that would interfere with swallowing or absorbing the study medication
• Pregnant or breast feeding women
• Previous or concurrent malignancy, except for the following circumstances: disease-free for at least three years and deemed by investigator to be a low risk for recurrence of that malignancy; individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin
• History of solid organ transplantation or other condition requiring teh use of immunosuppressive medications
• Uncontrolled hypertension
• A mean left ventricular ejection fraction (LVEF) less than 45%