A Randomized Phase II Study of OGX-011 in Combination with Docetaxel and Prednisone or Docetaxel and Prednisone Alone in Patients with Metastatic Castration Resistant Prostate Cancer Authors: Chi K, Hotte S, Yu E, Tu D, Eigl B, Tannock I, Saad F, North S, Powers J, E. Eisenhauer. Reviewed by: Dr. Stephanie Snow and Dr. Lori Wood Abstract: 5012 Date posted: June 2009

R Treatment A: OGX mg IV q week + Docetaxel 75 mg IV q3weeks + Prednisone 5 mg po bid Note: Patients received three loading doses of OGX-011 the week prior to starting Docetaxel Treatment B: Docetaxel 75 mg IV q3weeks + Prednisone 5 mg po bid Progressing, Metastatic Castration Resistant Prostate Cancer PSA ≥ 5 ECOG 0-2 Chemo naïve n=82

RESULTS Treatment A Treatment B p-value 1° Endpoint: Response Rate (%) ↓PSA ≥50% 5854NS PFS/TTP (median, mos) NS OS (median, mos)

STUDY COMMENTARY: What is OGX-011? OGX-011 (aka Custirsen) is an anti-sense molecule complementary to clusterin mRNA Clusterin is a chaperone protein which stabilizes cells under stress: Anti-apoptotic secretory form Expressed in many cancers. In prostate cancer: increased expression correlated with Gleason grade increased expression seen after hormonal treatment Chemotherapy can induce expression, thereby leading to drug resistance Down regulation may lead to increased treatment sensitivity

STUDY COMMENTARY Primary Endpoint was PSA response rate and there was no difference Mean number of cycles: Group A = 9, Group B = 7 Discontinued treatment due to AEs: Group A = 9%, Group B = 5% (possibly due to more cycles?) Group A had more lymphopenia (no associated increase in infections), infusion reactions (usually during loading doses) and newly elevated Creatinine from baseline (20% vs 5%) Discontinued treatment due to progression: Group A 7%, Group B 16% It was designed to be a non-comparative trial, but OS data intriguing (Group A 23.8 m, Group B 16.8 m) Given the study met the primary endpoint of ≥ 50% reduction in PSA in Group A and the intriguing survival data, there are plans for a Phase III comparative trial Correlative study showed a decrease in serum clusterin during cycle 1 consistent with a treatment response

BOTTOM LINE FOR CANADIAN MEDICAL ONCOLOGISTS Canadian trial from bench to bedside Combination makes biological sense Relatively well tolerated Phase III trial will be coming to a Canadian center near you!