Safety and Efficacy of SNX-5422 in Human Epidermal Growth Factor Receptor 2 (HER2) Positive Cancers

Inclusion Criteria:

* Males or non-pregnant, non-breastfeeding females .
* Confirmed diagnosis of locally advanced or metastatic breast, esophagogastric, urothelial, or non-small cell lung cancer.
* Histological or cytological confirmed carcinoma with HER2 amplification (IHC 3+ or FISH+ (\>2 HER2:CEP17)).
* Subjects with advanced or metastatic breast cancer must have received no more than 5 prior lines of anticancer therapy, including trastuzumab (but excluding hormonal treatments).
* Subjects with advanced or metastatic HER2 positive esophagogastric cancer must have received no more than 5 prior lines of anticancer therapy, including trastuzumab.
* Subjects with advanced or metastatic, urothelial carcinoma or non-small cell lung cancer must have received at least one, but no more than 5 prior lines of anticancer therapy.
* Measurable disease using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
* Life expectancy of at least 3 months.
* Karnofsky performance score ≥70.
* Adequate baseline laboratory assessments
* Recovered from toxicities of previous anticancer therapy, with the exception of CTCAE grade 1 sensory neuropathy.

Exclusion Criteria:

* Subjects with symptomatic central nervous system (CNS) metastases who are neurologically unstable
* Prior treatment with any Hsp90 inhibitor.
* Surgery, radiotherapy, or lesion ablative procedure to the only area of measurable disease.
* Major surgery within 4 weeks prior to first dose of SNX-5422.
* Treatment with chronic immunosuppressants (e.g., cyclosporine following transplantation).
* The need for treatment with medications with clinically-relevant metabolism by the cytochrome P450 (CYP) 3A4 isoenzyme within 3 hours before or after administration of SNX-5422.
* Screening ECG QTc interval ≥470 msec for females, ≥450 msec for males.
* At increased risk for developing prolonged QT interval
* Patients with chronic diarrhea or with grade 2 or greater diarrhea despite maximal medical management.
* Gastrointestinal diseases or conditions that could affect drug absorption, including gastric bypass.
* Gastrointestinal diseases that could alter the assessment of safety, including irritable bowel syndrome, ulcerative colitis, Crohn's disease, or hemorrhagic coloproctitis.
* History of documented adrenal dysfunction not due to malignancy.
* Known seropositive for human immunodeficiency virus (HIV) or hepatitis C virus (HCV).
* History of chronic liver disease.
* Active hepatitis A or B.
* Current alcohol dependence or drug abuse.
* Treatment with other anticancer drugs within 28 days or 5 half-lives of anticancer therapy (whichever is shorter), and treatment with any other investigational agent is prohibited from 30 days prior to the first dose of SNX-5422 and throughout the study
* Glaucoma, retinitis pigmentosa, macular degeneration, or any retinal changes detected by ophthalmological examination.
* Other serious concurrent illness or medical condition.
* Psychological, social, familial, or geographical reasons that would hinder or prevent compliance with the requirements of the protocol or compromise the informed consent process.