3566 Background: 17-DMAG binds to heat-shock protein 90, leading to degradation of oncogene client proteins, inhibiting tumor growth. Preclinically, 17-DMAG has potent antitumor activity. Methods: 17-DMAG was given by 1–2 hour infusion twice weekly for 4 weeks/28-day cycle. Starting dose: 1mg/m2/dose. Eligibility: ECOG = 2, adequate organ function. Exclusions: prolonged QTc/uncontrolled illness. An accelerated titration escalation design was used; one patient (pt)/dose level was entered until a single pt experienced dose-limiting toxicity (DLT) or 2 pts have grade (gr) = 2 toxicity during the first cycle. Ending the accelerated phase, it converts to a standard 3–6 pt/cohort design. Objectives: To determine the toxicity profile, pharmacokinetics (PK), pharmacodynamics (PD) and MTD of twice weekly 17-DMAG. Plasma samples collected before and up to 48 hours after 17-DMAG infusion were analyzed by LC-MS. Results: 23 pts were accrued and treated; Diagnosis: renal cell-1, pancreatic-2, medullary thyroid-1, NSCLC-3, colorectal -5, peritoneal mesotelioma-1 adrenocortical carcinoma-1, pheochromocytoma-2, malignant thymoma-1, melanoma-2, sarcoma-1, hepatocarcinoma-1 and head & neck -1 and ovary-1. 2 DLTs (gr 3 peripheral neuropathy and renal failure) were observed at 27 mg/m2/dose. Toxicities at the MTD dose (21 mg/m2/dose) have been acceptable: Myalgias/arthralgias being the most common. Other gr 1–2 toxicities included: diarrhea, weight loss, fatigue, elevated transaminases, hair loss, electrolyte abnormalities (hyponatremia and hypo/hyper-magnesemia) and leukocytopenia. PK is linear, with AUC and Cmax increasing as dose was escalated. Drug clearance is independent of dose, but highly variable (10.75 ± 5.56 L/hr/m2). Half-life: 10.0 to 31.7 h, with a median of 17.2 h. At the MTD: Cmax was 523.6 ± 265.3 ng/mL; Very high interindividual variability (CV = 70.3%) and a mean AUCinf of 2467.5 ± 1733.8 hr*ng/mL. Disease stabilization was achieved in a pt with mesothelioma (19 mos +) and another with head and neck cancer (8 mos +). Conclusions: We recommend 21mg/m2/dose twice weekly as the Phase II dose. The study continues to accrue at the MTD to collect paired biopsies for proteomic evaluation on Hsp90 client proteins analysis. No significant financial relationships to disclose.