900PD A Randomized Phase II Study of OGX-427 Plus Prednisone (P) Vs. P Alone in Patients (PTS) with Metastatic Castration Resistant Prostate Cancer (CRPC)

Background Heat Shock Protein 27 (Hsp27) is a multi-functional chaperone that regulates cell signaling and survival pathways implicated in cancer progression. In prostate cancer models, Hsp27 chaperones androgen receptor (AR) and enhances transactivation of AR-regulated genes. OGX-427 is a 2nd generation antisense that inhibits Hsp27 expression with in vitro and in vivo efficacy and was well tolerated in phase I studies. Methods Chemotherapy-naive pts with no/minimal symptoms were randomized to receive OGX-427 600 mg IV x 3 loading doses then 1000 mg IV weekly with 5 mg PO BID or P only. Primary endpoint was the proportion of pts progression free at 12 weeks (PCWG2 criteria). A 2-stage MinMax design (HO = 5%, HA > 20%, α = 0.1, β = 0.1) with 32 evaluable pts/arm provides 70% power to detect the difference at 0.10 (1-sided). Secondary endpoints include PSA decline, measurable disease response and circulating tumour cell (CTC) enumeration. Results 64 pts have been randomized; results of pts in the first stage are presented here (42 pts: 22 on OGX-427 + P, 20 on P). 10 pts are too early to evaluate (4) or non-evaluable (6) for week 12 progression. Baseline median age was 7 years (53-89); ECOG PS 0/1 in 67/33% of pts; median PSA of 66 (6-606); metastases in bone/lymph nodes/liver or lung was 74/57/10%; 19% had prior P treatment; 93% had ≥5 CTC/7.5 ml. Adverse events (AEs) have been mainly grade 1/2 OGX-427 infusion reactions. 6 pts had 15 grade 3/4 AEs considered OGX-427 related. There were 3 grade 4 AEs: hemolytic uremic syndrome, pulmonary embolus and dizziness. At week 12, the proportion of pts progression free was 12/17 (71%) (95% CI: 0.440, 0.897) in OGX427 + P treated pts and 6/15 (40%) (95% CI: 0.163, 0.677) in pts on P. A ≥50% PSA decline occurred in 11/22 (50%) of pts on OGX-427 + P and 4/20 (20%) pts treated with P. Measurable disease response occurred in 4/9 (44%) pts on OGX-427 + P (1CR, 3PR) and 0/12 pts on P. CTC conversion from ≥5 to <5/7.5 ml occurred in 12/22 (55%) pts on OGX-427 + P and 7/17 (41%) treated with P. Conclusions These data provide clinical evidence for the role of Hsp27 as a therapeutic target in prostate cancer and support continued evaluation of OGX-427 for pts with CRPC. Disclosure M.E. Gleave: Chief Scientific Officer: OnncoGenex Technologies Inc. Stock ownership: Oncogenex Technologies Inc. All other authors have declared no conflicts of interest.