Safety and Pharmacokinetics of Regorafenib and Cetuximab in Combination

Inclusion Criteria:

- Patients with histologically or cytologically confirmed, locally advanced or
metastatic solid tumors who are not candidates for standard therapy or in whom
regorafenib or cetuximab is considered a standard treatment. Patients with metastatic
colorectal cancer (mCRC) must have a record of K-ras gene mutational analysis
available and no K-ras mutation is present.

- Male or female patients ≥ 18 years of age

- Women of childbearing potential must have a blood or urine pregnancy test performed a
maximum of 7 days before start of study treatment, and a negative result must be
documented before start of study treatment

- Life expectancy of at least 3 months

- Adequate bone marrow, liver and renal function as assessed by the following laboratory
requirements conducted within 7 days of starting the study treatment:

- Platelet count ≥ 100,000/cubic millimeters (mm3), hemoglobin (Hb) ≥ 8.5 g/dl,
leukocyte count > 3,000/mm3, absolute neutrophil count (ANC) ≥ 1,000/mm3

- Total bilirubin ≤ 1.5 x the upper limit of normal (ULN). Mildly elevated total
bilirubin (< 6 mg/dL) is allowed if Gilbert's syndrome is documented.

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN
(≤ 5 x ULN for subjects with liver involvement of their cancer)

- Alkaline phosphatase limit ≤ 2.5 x ULN (≤ 5 x ULN for subjects whose cancer
involves their liver).

- Amylase and lipase ≤ 1.5 x ULN

- Serum creatinine ≤ 1.5 times ULN and creatinine clearance (CLcr) ≥ 30 mL/min
according to the Cockroft-Gault formula

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

Exclusion Criteria:

- Prior treatment with Regorafenib

- Prior discontinuation of cetuximab treatment due to toxicity or intolerance of
cetuximab

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
before start of study medication

- Non-healing wound, ulcer, or bone fracture

- Systemic anticancer therapy within 28 days

- Patients unable to swallow and retain oral medications