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OncoGenex Pharmaceuticals, Inc. Message Board

  • strikepackage strikepackage May 20, 2012 8:57 PM Flag

    ASCO Abstract

    Any thoughts on the ASCO abstract for OGX-427?

    Prostate Cancer

    Genitourinary Cancer

    2012 ASCO Annual Meeting

    Abstract No:

    J Clin Oncol 30, 2012 (suppl; abstr 4514)

    Attend this session at the
    ASCO Annual Meeting!
    Session: Genitourinary Cancer (Prostate)

    Type: Oral Abstract Session

    Time: Tuesday June 5, 9:45 AM to 12:45 PM

    Location: E Arie Crown Theater

    Personalize your Annual Meeting experience with a suggested or customized itinerary!
    Author(s): Kim N. Chi, Sebastien J. Hotte, Susan Ellard, Joel Roger Gingerich, Anthony Michael Joshua, Evan Y. Yu, Martin Edwin Gleave; British Columbia Cancer Agency, Vancouver, BC, Canada; Juravinski Cancer Centre, Hamilton, ON, Canada; Cancer Centre for Southern Interior, Kelowna, BC, Canada; University of Manitoba, Winnipeg, MB, Canada; Princess Margaret Hospital, Toronto, ON, Canada; Fred Hutchinson Cancer Research Center, Seattle, WA; Vancouver Prostate Centre, Vancouver, BC, Canada

    Abstract Disclosures


    Background: Heat Shock Protein 27 (Hsp27) is a multi-functional chaperone protein that regulates cell signaling and survival pathways implicated in cancer progression. In prostate cancer models, Hsp27 complexes with androgen receptor (AR) and enhances transactivation of AR-regulated genes. OGX-427 is a 2nd generation antisense oligonucleotide that inhibits Hsp27 expression with in vitro and in vivo efficacy and was well tolerated with single agent activity in phase I studies. Methods: Chemotherapy-naïve pts with no/minimal symptoms were randomized to receive OGX-427 600 mg IV x 3 loading doses then 1000 mg IV weekly with P 5 mg PO BID or P only. Primary endpoint was the proportion of pts progression free (PPF) at 12 weeks (PCWG2 criteria). A 2-stage MinMax design (H0 = 5%, HA >20%, α=0.1, β=0.1) with 32 pts/arm provides 70% power to detect the difference at 0.10 1-sided significance. Secondary endpoints include PSA decline, measurable disease response, and circulating tumour cell (CTC) enumeration. Results: 38 pts have been enrolled; 1st stage of accrual completed with 2nd stage accruing. In the 1st 32 pts randomized (17 to OGX-427+P, 15 to P), baseline median age was 71 years (53-89), ECOG PS 0 or 1 in 66% and 34% of pts, median PSA 66 (6-606), metastases in bone/lymph nodes/liver or lung was 75/56/9%, 31% had prior P treatment, and 93% had ≥5 CTC/7.5 ml. Predominantly grade 1/2 infusion reactions (chills, diarrhea, flushing, nausea, vomiting) occurred in 47% of pts receiving OGX-427+P. One pt on OGX-427+P developed hemolytic uremic syndrome. A PSA decline of ≥50% occurred in 41% of pts on OGX-427+P, and 20% of pts treated with P. A measurable disease partial response was seen in 3/8 (38%) evaluable pts on OGX-427+P and 0/9 pts on P. CTC conversion from ≥5 to <5/7.5 ml occurred in 50% of pts on OGX-427+P and 31% treated with P. Thus far, in 26 evaluable pts the PPF at 12 weeks was 71% (95% CI: 42-92) in OGX-427+P treated pts and 33% (95% CI: 10-65) in pts on 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. Funded by a grant from the Terry Fox Research Institute.

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