A PHASE I, OPEN-LABEL, MULTICENTER, 3- PERIOD, FIXED-SEQUENCE STUDY TO INVESTIGATE THE EFFECT OF VEMURAFENIB ON THE PHARMACOKINETICS OF SINGLE DOSE OF TIZANIDINE (A CYP1A2 SUBSTRATE) IN PATIENTS WITH BRAFV600 MUTATION-POSITIVE METASTATIC MALIGNANCY

Inclusion Criteria:

- Adult patients, 18 to 70 years of age, inclusive

- Patients with either unresectable Stage IIIc or IV metastatic melanoma positive for
the BRAFV600 mutation or other malignant tumor type which harbors a V600 activating
mutation of BRAF, as determined by Cobas 4800 BRAFV600 Mutation Test or a DNA
sequencing method

- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

- Life expectancy >/= 12 weeks

- Patient has not consumed tobacco or nicotine-containing products for 6 weeks prior to
first dose of study drug, and must agree to refrain from such products while on study

- Adequate hematologic, renal and liver function

Exclusion Criteria:

- Prior treatment with vemurafenib or other BRAF inhibitor within 42 days of Day 1,
period A

- History of or current clinically significant cardiac or pulmonary dysfunction,
including current uncontrolled Grade >/= 2 hypertension or unstable angina

- Current dyspnea at rest due to complications of advanced malignancy or any
requirement for supplemental oxygen

- Active central nervous system lesions (i.e. patients with radiographically unstable,
symptomatic lesions)

- Patients with CYP2A2 gene mutation (-3113G->A)

- Allergy or hypersensitivity to vemurafenib or tizanidine formulations

- Current severe uncontrolled systemic disease

- Inability or unwillingness to swallow pills

- History of malabsorption or other condition that would interfere with enteral
absorption of study treatment

- History of clinically significant liver disease including cirrhosis), current alcohol
abuse, or HIV infection requiring antiretroviral treatment, AIDS-related illness, or
active hepatitis B or C

- Active autoimmune disease

- Pregnant or breastfeeding women