Safety and Pharmacology of SNX-5422 Plus Carboplatin and Paclitaxel in Subjects With Solid Tumors

Inclusion Criteria:

* Males or non-pregnant, non-breastfeeding females 18 years-of-age or older.
* Pathologic evidence of Small Cell Lung Cancer, or Non-Small Cell Lung Cancer.
* No more than one prior line of antitumor therapy for metastatic disease, excluding prior treatment with tyrosine kinase inhibitors. An interval of at least 1 week is required for washout of the tyrosine kinase inhibitor.
* Measurable disease using RECIST criteria (version 1.1).
* Life expectancy of at least 3 months.
* Karnofsky performance score ≥70.
* Adequate baseline laboratory assessments, including:

  * Absolute neutrophil count (ANC) ≥1.5 x 109/L.
  * WBC \>3000/microliter.
  * Platelet count of ≥100 x 109/L.
  * Total bilirubin level ≤1.5 times institutional upper limit of normal (ULN), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤2.0 x ULN except in subjects with known hepatic metastasis, where AST or ALT can be ≤5.0 x ULN.
  * Hemoglobin ≥9 mg/dL.
  * Estimated creatinine clearance of ≥40 mL/min
* Recovered from toxicities of previous anticancer therapy to CTCAE Grade ≤ 1 with the exception of alopecia.
* Signed informed consent form (ICF)
* Subjects with reproductive capability must agree to practice adequate contraception methods.
* Adequate venous access

Exclusion Criteria:

* CNS metastases that are symptomatic and /or requiring steroids.
* Prior treatment with any Hsp90 inhibitor.
* Major surgery or significant traumatic injury within 4 weeks of starting study treatment.
* 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, including hypokalemia or hypomagnesemia, unless corrected to within normal limits prior to first dose of SNX-5422; congenital long QT syndrome or a history of torsade de pointes; currently receiving anti-arrhythmics or other medications that may be associated with QT prolongation
* 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.
* Radiation treatment within 2 weeks.
* 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.