Inclusion Criteria:

- Must have cytologically or histologically-confirmed unresectable melanoma that
harbors a BRAF V600 mutation determined by pyrosequencing assay, meeting one of the
following American Joint Committee on Cancer (AJCC) staging criteria:

- AJCC Stage IV (Tany, Nany, M1a, b, or c)

- AJCC Stage III B or C with unresectable nodal/locoregional involvement

- Adequate hepatic, renal, and bone marrow function as defined by the following
parameters obtained within 2 weeks prior to initiation of study treatment:

- Hematologic Criteria: leukocytes ≥3,000/mcL; absolute neutrophil count
≥1,500/mcL; platelets ≥100,000/mcL

- Renal Criteria: serum creatinine within normal institutional limits or a
creatinine clearance ≥60 mL/min for patients with creatinine levels above
institutional normal

- Hepatic Criteria: aspartate aminotransferase (AST)/alanine transaminase (ALT)
≤2.5 X institutional upper limit of normal; if liver metastasis present, then
AST/ALT may be less than or equal to 5 times the upper limit of normal

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Willing to give written informed consent per institutional guidelines and must be
able to adhere to dose and visit schedules

- Female and male participants must agree to use a medically acceptable method of birth
control prior to screening and agree to continue its use throughout the study.
Females of childbearing potential should be counseled in the appropriate use of birth
control while on this study.

- Treatment-naïve and previously treated patients will be included; however, patients
may not have received a BRAF or HSP90 inhibitor in the past.

- Patients must be at least 4 weeks from any prior systemic therapy (6 weeks for
nitrosoureas or mitomycin C), surgery or radiation.

- Must have measurable disease as defined by RECIST 1.1

Exclusion Criteria:

- Females who are pregnant, intend to become pregnant or are nursing. Females with
child-bearing potential must have a negative pregnancy test within one week of
enrollment.

- Previously treated with BRAF or HSP90 inhibitor therapy

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier.

- Patients who are receiving any other investigational agents.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition (i.e. ethanol) to XL888 or vemurafenib (i.e., ethanol).

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris,
uncontrolled or symptomatic cardiac arrhythmia, or psychiatric illness/social
situations that would limit compliance with study requirements

- HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with XL888 and vemurafenib.

- Untreated or uncontrolled brain metastases or evidence of leptomeningeal disease.
Brain metastases that have been appropriately treated with radiation and/or surgery
will be allowed as long as the central nervous system (CNS) disease has been stable
for at least 4 weeks post-treatment.

- Must be at least 3 years from any prior malignancy and have no evidence of the
malignancy at the time of enrollment. Patients with adequately treated squamous cell
or basal cell carcinomas of the skin, multiple primary melanomas, or any carcinoma in
situ will be allowed.

- Corrected QT interval (QTc) greater than 460 ms at baseline