RTA 408 in the Treatment of Advanced Solid Tumors (NSCLC & Melanoma) - DISCOVER

Inclusion Criteria: 1. Adult male and female patients (18 to 75 years of age, inclusive); 2. Histologically or cytologically documented advanced NSCLC who have Stage IIIB/Stage IV disease, or recurrent disease following radiation therapy or surgical resection or advanced, unresectable (Stage III) or metastatic (Stage IV) melanoma; 3. Patients must have experienced disease recurrence or progression during or after prior treatment with one or more prior standard systemic therapies; 4. Patients with epidermal growth factor receptor (EGFR) overactivity mutations or anaplastic lymphoma kinase (ALK) rearrangements must have received tyrosine-kinase inhibitor (TKI) therapy prior to consideration for enrollment; 5. Life expectancy \> 3 months; 6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2; 7. Have discontinued previous treatments for cancer and recovered from all acute toxic effects of prior systemic therapy (except alopecia) to grade ≤1; 8. Have adequate bone marrow reserve and organ function at screening as follows: 1. Hematologic: Absolute neutrophil count \> 1.5 x 109/L, platelets \> 100 x 109/L, hemoglobin ≥ 9 g/dL (Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. The first dose of study drug must not begin until 5 days after the erythrocyte transfusion); 2. Hepatic: total bilirubin ≤ 1.5 X ULN, ALT and AST ≤ ULN; 3. Renal: estimated glomerular filtration rate (eGFR) using the modification of diet in renal disease (MDRD) formula ≥ 50 mL/min; 9. Willing to practice methods of birth control (both males who have partners of childbearing potential and females of childbearing potential) from screening through 3 months after taking the final dose of RTA 408; 10. Female patients of childbearing potential must be non-pregnant, non-lactating, and have a negative pregnancy test result prior to enrollment in the study; Exclusion Criteria: 1. Concurrent active malignancy other than adequately treated nonmelanomatous cell skin cancers, superficial bladder cancer, or carcinoma in situ of the cervix or breast; 2. Patients who previously had brain metastases (screening not required) unless they have met all of the following criteria: 1. Patient had a resection and/or completed a course of cranial irradiation; and 2. Patient has no worsening central nervous system symptoms; and 3. Patient has discontinued all corticosteroids for that indication for at least 2 weeks; 3. Cardiovascular abnormalities: 1. Evidence of poor cardiovascular function defined as b-type natriuretic peptide (BNP) \> 100 pg/mL, or history of congestive heart failure, unstable angina, uncontrolled hypertension, or clinically significant ventricular arrhythmias at screening; 2. Myocardial infarction within 6 months prior to screening; 3. QTcF interval on electrocardiogram (ECG) at screening \> 450 msec for males or \> 460 for females; 4. Known hepatic impairment including cirrhosis, known renal impairment including renal insufficiency or glomerulonephritis and severe cerebral or peripheral vascular disease; 5. Any gastrointestinal disorder with diarrhea as a major symptom, such as Crohn's, or pre- existing chronic diarrhea CTCAE Grade ≥ 2 of any etiology. Included are malabsorption disorders or surgical procedures that in the opinion of the investigator may affect absorption of study drug; 6. Known active fungal, bacterial, and/or known viral infection including human immunodeficiency (HIV) or viral (A, B, or C) hepatitis (screening is not required).; 7. Major surgery within 21 days before Study Day 1; 8. Have taken any of the following drugs within 7 days prior to Study Day 1: 1. Sensitive substrates for cytochrome P450 2C8 or 3A4 (e.g., repaglinide, midazolam, sildenafil); 2. Substrates for p-glycoprotein transporter (e.g., ambrisentan, digoxin), OCT1 transporter (e.g., metformin), OAT1 transporter (e.g., captopril, furosemide, methotrexate), and OATP1B3 transporter (e.g., atorvastatin, rosuvastatin, valsartan); 9. Known or suspected active drug or alcohol abuse;