PD32-03 A PHASE 2 OPEN-LABEL TRIAL OF GTX-758 IN MEN WITH CASTRATION-RESISTANT PROSTATE CANCER, FINAL ANALYSIS OF THE PRIMARY ENDPOINT (2016)

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) III1 Apr 2016PD32-03 A PHASE 2 OPEN-LABEL TRIAL OF GTX-758 IN MEN WITH CASTRATION-RESISTANT PROSTATE CANCER, FINAL ANALYSIS OF THE PRIMARY ENDPOINT William Aronson, Evan Yu, Michael Hancock, Tamás Babicz, Ronald Tutrone, Christopher Ng, Laurence Belkoff, Zsuzsanna Pápai, Lajos Géczi, and Robert Getzenberg William AronsonWilliam Aronson More articles by this author , Evan YuEvan Yu More articles by this author , Michael HancockMichael Hancock More articles by this author , Tamás BabiczTamás Babicz More articles by this author , Ronald TutroneRonald Tutrone More articles by this author , Christopher NgChristopher Ng More articles by this author , Laurence BelkoffLaurence Belkoff More articles by this author , Zsuzsanna PápaiZsuzsanna Pápai More articles by this author , Lajos GécziLajos Géczi More articles by this author , and Robert GetzenbergRobert Getzenberg More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.679AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recently approved agents that target the androgen receptor pathway emphasize the importance of the persistent activity of the androgen receptor pathway in castration-resistant prostate cancer (CRPC). This raises the possibility that agents with distinct mechanisms of action may add value. GTx-758 is a selective ERα agonist that can increase SHBG and therefore reduce biologically active testosterone (T) levels. Reported here are the results, including the final primary endpoint analysis, from the 250 mg daily GTx-758 cohort of a Phase 2 clinical trial in men on LHRH agonists that developed CRPC. METHODS This phase 2 open label trial (G200712, NCT01615120) treated men with high risk nmCRPC or mCRPC with T levels <50 ng/dL who continued to receive their current form of ADT along with either 125 mg or 250 mg of GTx-758 daily, for at least 90 days. The primary endpoint was the proportion of men with a PSA decline ≥50% by day 90, while secondary endpoints included serum total and free T, sex hormone binding globulin (SHBG), bone turnover markers and hot flashes. RESULTS The 250 mg cohort (n=39) has completed the time period for assessment of the primary endpoint. Ten of the 39 (26%) subjects exhibited a ≥50% decrease in PSA by Day 90, with 11/39 (28%) by Day 120, while 18/39 (46%) had PSA declines of ≥30%. Median SHBG levels increased 301% of baseline, confirming the principal mechanism of drug action. While on study, median free T decreases of 44% were observed across all subjects and 20/26 (77%) of the subjects with baseline serum free T levels >0.7 pg/ml fell below this level. Therefore, 250 mg GTx-758 decreased free testosterone levels in an additive fashion to their existing LHRH therapy. The bone turnover biomarker, C-telopeptide, decreased in 79% of the subjects. 250 mg of GTx-758 has been generally well tolerated with two reported possibly drug related SAEs (VTE and MI). CONCLUSIONS In this Phase 2 trial, 250 mg daily GTx-758 has activity, likely mediated by lowering free T levels in patients with CRPC on LHRH therapy, and may provide amelioration of estrogen deficiency side effects associated with ADT. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e761-e762 Advertisement Copyright & Permissions© 2016MetricsAuthor Information William Aronson More articles by this author Evan Yu More articles by this author Michael Hancock More articles by this author Tamás Babicz More articles by this author Ronald Tutrone More articles by this author Christopher Ng More articles by this author Laurence Belkoff More articles by this author Zsuzsanna Pápai More articles by this author Lajos Géczi More articles by this author Robert Getzenberg More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...