245 Background: Gemcitabine (GEM) monotherapy for PDA has modest activity. 17-N-Allylamino-17-demthoxygeldanamycin (Tanespimycin/17AAG), is an HSP90 inhibitor, which results in degradation of a number of client proteins such as RAF and Akt. Arlander et al (J Biol Chem. 2003 278:52572-7) have demonstrated that 17AAG targeting of HSP90 leads to Chk1 degradation. Chk1 is upregulated with GEM treatment which affects cell survival (Karnitz et al. Mol Pharmacol. 2005 68:1636-44). In vitro, the combination demonstrated in vitro synergy. Thus the potential clinical activity in pancreatic cancer of the combination was explored. Methods: A phase II multicenter prospective study was performed using GEM 750 mg/m2 d1,8 and 17AAG 154 mg/m2 d2,9 on a 21 day cycle, as defined in a previous phase I trial. Patients with stage IV PDA, with adequate liver, kidney function and counts, ECOG 0-2 and no prior therapy for metastatic disease were eligible. The primary endpoint of 60% overall survival at 6 months was considered of clinical interest. Sixty-six patients were planned for accrual, and an interim analysis was planned after 25 evaluable patients. Informed, written consent was obtained from all pts. Results: Due to lack of drug availability and failure to achieve the planned endpoint, accrual was halted at 21 pts, enrolled from 5/08 to 9/10, of which 20 were evaluable (1 cancelled prior to treatment). Median age was 61.5 yrs., 55% were male, PS 0 (50%), 1 (45%), 2 (5%); 95% were non-Hispanic white, 1 was African American. Two had received adjuvant therapy for PDA. Tolerability was moderate, with 13 pts (65%) having > grade 3 adverse event (AE), with 15% gr 4 AEs and 0% gr 5. Nausea (20%), vomiting (20%), constipation (15%), dehydration (15%), and anorexia (10%), were the most common non-heme AEs. Lymphopenia (15%), leukopenia (10%) and neutropenia (10%) were common grade 3 hematologic AEs. No complete or partial responses were seen. 40% of patients were alive at 6 months, with a median OS of 5.4 months. Conclusions: HSP 90 inhibitor 17AAG in combination with GEM does not show activity for treatment of PDA. Further trials should not be pursued with this combination. Supported by N01-CM-62205. Clinical trial information: NCT00577889.