Phase I study of OGX-427 shows evidence of activity in bladder cancer
OncoGenex Pharmaceuticals has announced preliminary results from an investigator-sponsored phase I study of patients with superficial bladder cancer with its investigational compound OGX-427, designed to inhibit the production of Hsp27.
Hsp27 is a cell-survival protein expressed in many types of cancers including prostate, bladder, breast and non-small cell lung cancer. Overexpression of Hsp27 is thought to be an important factor leading to the development of treatment resistance and is associated with negative clinical outcomes in patients with various tumor types.
In patients with superficial bladder cancer, preliminary results demonstrated a trend toward decreased levels of Hsp27 and increased tumor cell death rates after intravesical treatment with OGX-427. Additionally, of the 15 patients treated with OGX-427, 33% had complete responses with no pathologic evidence of disease observed in post-surgical tissue following four doses of OGX-427 administered intravesically over an eight-day period. The absence of residual disease post OGX-427 intravesical treatment prevented evaluation of Hsp27 levels and tumor cell death rates within tumor cells in these patients.
"The primary objective of this study was to evaluate pharmacokinetic and pharmacodynamic effects of OGX-427 intravesical administration.
Interestingly, the complete response rate observed to date is higher than expected," said Dr. Alan So, the study's principal investigator and a urologic oncologist at the Vancouver Prostate Center at The University of British Columbia. "We will continue enrolling additional patients with larger tumors and continue to evaluate the effect of higher OGX-427 doses on Hsp27 levels."
No significant drug-related adverse events were reported and no dose-limiting toxicity has been observed. One patient developed gross hematuria (grade I) within 24 hours of administration of OGX-427 that spontaneously resolved. Authors concluded OGX-427 was well tolerated with minimal toxicity.