7516 Background: IPI-504, a water-soluble analog of 17-allylamino-17-demethoxygeldanamycin (17-AAG), is an intravenously (IV) administered heat shock protein 90 (Hsp90) inhibitor that causes degradation of a variety of mutated or amplified oncoproteins. The combination of IPI-504 with taxanes has demonstrated additive activity in murine xenograft tumor models. Methods: An expansion of a Phase Ib trial was undertaken to evaluate IPI-504 in combination with docetaxel in pts with NSCLC and Karnofsky performance status of ≥70. Pts had pathologically confirmed metastatic NSCLC; all had received 1 to 2 prior chemotherapy regimens without prior docetaxel. Docetaxel 75 mg/m2 IV was given once every three weeks (wks), while IPI-504 300 mg/m² IV was administered once per wk. All pts were evaluated for safety, pharmacokinetics and tumor response (RECIST). Archival tissue samples were required for KRAS genotyping. Results: The 23 pts included in this analysis received an average of 4 cycles (range 1-13) on study. Median age was 61 years, 13 (57%) were female, and 18 (78%) were current or former smokers, with a median tobacco exposure of 30 pack-years. The majority of adverse events were Grade 1 or 2, and the most common treatment-related adverse events were fatigue (57% total, 4% ≥Grade 3), diarrhea (35%, 9%), nausea (30%, 13%), vomiting (30%, 13%), neutropenia (30%, 30%), and anemia (26%, 4%). Docetaxel pharmacokinetics were unaltered by IPI-504 co-administration. 6 of the 23 pts (26%) had a partial response (PR), including 3 of 7 pts with squamous cell carcinoma. Efficacy analysis in overall population and exploratory subgroups is below (Table). Conclusions: IPI-504 in combination with docetaxel was well tolerated and resulted in clinical activity in pts with pretreated, metastatic NSCLC. A randomized trial is ongoing to evaluate this combination compared to docetaxel plus placebo in this pt population. Clinical activity. Patients n ORR n, (%) Previously treated NSCLC 23 6 (26) Current or former smokers 18 6 (33) Squamous cell carcinoma 7 3 (43) KRAS wild type 13 4 (31) Abbreviation: ORR, overall response rate (all PRs).