A Phase 1 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