Background: Heat shock protein 27 (Hsp27) is over-expressed in PC, enabling tumor growth and metastasis. A is an antisense oligonucleotide that binds to Hsp27 mRNA and inhibits production of Hsp27 protein. This randomized phase II trial evaluates the efficacy of gem/nab-P plus A or Pl in pts with mPC. Methods: Pts with untreated mPC were randomized 1:1 to Arm A (gem, nab-P, A) or Arm B (gem, nab-P, Pl). 3 loading doses of 600mg A IV or Pl IV were given, then 600 mg A or Pl weekly with chemotherapy in 28 day cycles. Both arms received gem 1000mg/m² IV, nab-P 125mg/m² IV days 1, 8, and 15. Restaging was every 2 cycles. Serum Hsp27 levels were collected at baseline and on treatment. Primary endpoint compared overall survival (OS); secondary endpoints were progression free survival (PFS), response rate (RR), CA 19-9 response, and toxicity. Results: 132 pts were randomized: median age 66 yrs, 57% male, 47% ECOG 0. Demographics were similar for both arms. 36% of pts on Arm A and 48% of pts Arm B discontinued due to progressive disease, and 24% and 14% due to adverse events (AEs). There was a higher incidence of ≥Grade (G) 4 and serious adverse events (SAEs) in Arm A. The most frequently reported G 3/4 treatment-related AEs were anemia (20%), neutropenia (17%), and fatigue (16%) on Arm A and anemia (27%), neutropenia (19%), and thrombocytopenia (13%) on Arm B. Overall RR was 18% on each arm. With a median f/u of 9.1 mos, median PFS and OS are 2.7 and 5.2 mos on Arm A and 3.8 and 6.9 mos on Arm B (p=NS). Correlative analyses between Hsp27 expression and clinical outcomes will be presented. In a statistical model using only Arm B data, 3 base attributes, ECOG >0, liver mets, and neutrophil levels had a strong prognostic relationship to OS. Conclusions: This study showed no improvement in clinical outcomes adding A to gem plus nab-p. G 4 AEs and SAEs were increased with A. We await analysis for Hsp 27 and CA 19-9 levels and further analysis to identify any pt subgroup who might have benefited from the experimental treatment. Clinical trial information: NCT01844817