• To assess the safety and tolerability of XL228 administered as a weekly 1-hour intravenous (IV) infusion in subjects with advanced malignancies.
  
• To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of XL228 administered as a weekly 1-hour IV infusion in subjects with advanced malignancies.
  

• To evaluate plasma pharmacokinetics of XL228 administered as a weekly 1-hour IV infusion in subjects with advanced malignancies.
  

Inclusion Criteria:

• The subject has a histologically confirmed solid tumor that is metastatic or unresectable, lymphoma, or multiple myeloma, and for which standard curative or palliative measures do not exist or are no longer effective, and there are no known therapies to prolong survival.
• The subject has disease that is assessable by tumor marker, clinical laboratory, physical, or radiologic means.
• The subject is ≥18 years old.
• The subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• The subject has adequate organ and marrow function.
• The subject is capable of understanding the informed consent document and has signed the informed consent document.
• Sexually active subjects (male and female) must use medically acceptable methods of contraception during the course of the study.
• Female subjects of childbearing potential must have a negative serum pregnancy test at screening.

Exclusion Criteria:

• The subject has received anticancer treatment (eg, chemotherapy, radiotherapy, cytokines, investigational agent, or hormones) within 14 days before the first dose of study drug.
• The subject has received radiation to >25% of his or her bone marrow within 30 days of treatment with XL228.
• The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Grade ≤1 from adverse events (AEs) due to investigational or other agents administered more than 14 days prior to study enrollment.
• The subject has a primary brain tumor or known brain metastases.
• The subject has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, diabetes, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
• The subject has a psychiatric illness or social situation that would limit compliance with study requirements.
• The subject is pregnant or breastfeeding.
• The subject is known to be positive for the human immunodeficiency virus (HIV).
• The subject has a known allergy or hypersensitivity to components of the XL228 formulation.
• The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.