Safety and Pharmacology Study of SNX-5422 in Subjects With Refractory Solid Tumor Malignancies

Correlation has been observed between Hsp90 client protein level changes and functional
effects in cells in in vitro studies of SNX-5422, supporting inhibition of Hsp90 as the
mechanism of action for this compound. SNX-5422 has demonstrated significant antitumor
activity in mouse xenograft models of human tumors, including breast (BT474, MX-1), colon
(HT29), prostate (PC3), and melanoma (A375) with multiple oral dosing regimens. This study
will employ critical risk management features including the use of the NCI Common
Terminology Criteria for Adverse Events (CTCAE) Version 4.03, which provides a scale for
consistently grading the severity of AEs, toxicity criteria analyses for dose escalation,
frequent laboratory and clinical observations, correlation of AEs with plasma concentrations
of drug, monitoring of the QTc interval at appropriate time points, and a conservative
dose-escalation scheme.

Inclusion Criteria:

- >18 years old histologically confirmed solid tumor malignancy refractory to available
therapy or for which no therapy is available adequate organ function

Exclusion Criteria:

- CNS malignancy significant GI disease at risk for prolonged QT interval