Safety Study of Pharmacokinetics of XL888 in Adults With Solid Tumors

Inclusion Criteria:

1. Subject has a histologically-confirmed tumor that is metastatic or unresectable and is no longer responding to therapies known to prolong survival or to other standard therapies, or has disease for which no effective therapy exists.

2. For subjects enrolling in the maximum tolerated dose expansion cohorts:

   • Subject has documented evidence of Her2-overexpressing tumor; OR
   • Subject has NSCLC that has progressed after a prior response to erlotinib or gefitinib; OR
   • Subject has histologically-confirmed, metastatic melanoma.
   • For subjects in the expansion cohorts A and C: tumor tissue must be accessible for biopsy and subjects must be willing to undergo tumor biopsy.
3. The subject is ≥ 18 years old.
4. The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
5. The subject's weight is ≥ 40 kg.
6. The subject has adequate organ and marrow function.
7. The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document.
8. Sexually active subjects (male and female) must use accepted methods of contraception during the course of the study and for 3 months after the last dose of XL888.
9. Female subjects of childbearing potential must have a negative pregnancy test at screening.

Exclusion Criteria:

1. The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic therapy (cytokines, antibodies) within 3 weeks (or nitrosoureas or mitomycin C within 6 weeks) before the first dose of XL888.
2. The subject has received prior treatment with a small molecule kinase inhibitor (including an investigational kinase inhibitor) or hormonal therapy within 14 days before the first dose of XL888.
3. The subject has received any other type of investigational agent within 28 days before the first dose of study treatment.
4. The subject has a previously-identified allergy or hypersensitivity to components of the study treatment formulation.
5. The subject has not recovered from clinically-meaningful toxicity due to prior therapy.
6. The subject has been previously treated with an HSP90 inhibitor
7. The subject has untreated or uncontrolled brain metastases or evidence of leptomeningeal involvement of disease.
8. The subject is currently receiving anticoagulation with therapeutic dose of warfarin.
9. The subject has uncontrolled intercurrent illness including, but not limited to: ongoing or active infection; diabetes mellitus; hypertension; symptomatic congestive heart failure, unstable angina pectoris, stroke or myocardial infarction within 3 months.
10. The subject has a baseline corrected QT interval (QTc) > 460 ms.
11. The subject is pregnant or breastfeeding.
12. The subject is known to be positive for the human immunodeficiency virus (HIV).
13. The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.