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.

Exclusion Criteria:

* Anti-cancer chemotherapy, immunotherapy, or investigational agents within four weeks of the first dose of ARQ 736
* Major surgery or radiotherapy within two weeks of the first dose of ARQ 736
* Brain metastases that are progressing or have been documented to be stable for less than six weeks, or for which systemic corticosteroids are required
* History of allergic reactions attributed to compounds of similar chemical or biologic composition as ARQ 736
* Unable or unwilling to swallow the complete daily dose of ARQ 736
* Significant gastrointestinal disorder(s), in the opinion of the Investigator, (e.g., Crohn's disease, ulcerative colitis, extensive gastric resection)
* History of myocardial infarction (MI) within 6 months of the administration of the first dose of ARQ 736 (MI occurring \> 6 months of the first dose of ARQ 736 will be permitted)
* History of congestive heart failure defined as Class II to IV per New York Heart Association (NYHA) classification within 6 months of the administration of the first dose of ARQ 736
* Previous malignancy within 2 years of the first dose of ARQ 736, except carcinoma in-situ of the cervix
* Concurrent uncontrolled illness, including but not limited to:
* Ongoing or active infection, including human immunodeficiency virus (HIV) infection or bleeding
* Psychiatric illness/substance abuse/social situation that would limit compliance with study requirements
* Blood transfusion within five days prior to blood draw being used to confirm eligibility