Dose Escalation Study of ARQ 736 in Adult Subjects With Advanced Solid Tumors Harboring BRAF and/or NRAS Mutations

Inclusion Criteria

• •Signed written informed consent granted prior to initiation of any study-specific procedures
• •Male or female subjects of ≥ 18 years of age
• •All subjects must be positive for a BRAF and/or NRAS mutation
• •Histologically or cytologically confirmed locally advanced, inoperable or metastatic solid tumors
• •Failure to respond to at least one prior systemic therapy (including previous treatment with BRAF inhibitors) or to whom standard or curative therapy does not exist
• •Life expectancy of greater than three months
• •Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2
• •Measurable disease as defined by Response Evaluation Criteria in Solid Tumors
• •Hemoglobin (Hgb) ≥10 g/dl
• •Absolute neutrophil count (ANC) ≥1.5 x 10\^9/L
• •Platelet count ≥100 x 10\^9/L
• •Total bilirubin ≤1.5 × upper limit of normal (ULN)
• •Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 × ULN (≤5 x ULN for subjects with liver metastases)
• •Serum creatinine ≤1.5 × ULN or creatinine clearance \>60 mL/min/1.73 m\^2 for subjects with creatinine levels above institutional normal
• •Left Ventricular Ejection Fraction (LVEF) ≥ the institutional lower limit normal (ILLN)
• •Male or female subjects of child-producing potential must agree to use double-barrier contraceptive measures, oral contraception or avoidance of intercourse during the study and for 30 days after the last dose of ARQ 736
• •Females of childbearing potential must have a negative serum pregnancy test within seven days prior to the first dose of ARQ 736
• •Must agree to have tumor and/or skin (nevi) biopsy at baseline and on Day 15 or Day 22 of Cycle 1. Tumor biopsy will be done if the subject has a lesion for which in the Investigator's opinion a non- or minimally invasive tumor biopsy may be performed. If tumor biopsy is not available, skin (nevi) biopsy should be performed.