923P - GTX-758, An Oral ERa Agonist, Increases Sex Hormone Binding Globulin, Reduces Free T and Decreases PSA in Patients with Castration Resistant Prostate Cancer

Abstract

ABSTRACT Introduction & objective GTx-758 is an oral, selective estrogen receptor α agonist, which induces sex hormone binding globulin (SHBG) and subsequently reduces free testosterone (FT) to levels below that achieved with LHRH agonists. Such agonists represent a distinct class of agents with the potential to impact men with advanced prostate cancer. Herein we report the results of a proof of concept trial of GTx-758 in patients who developed castration resistant prostate cancer (CRPC) while on androgen deprivation therapy (ADT). Methods Men (n = 9) receiving ADT and developed CRPC, were enrolled in a Phase II open label study to 2000 mg GTx-758 daily. Primary endpoint was the proportion of subjects with a ≥ 50% reduction in prostate specific antigen (PSA) from Day 1. Secondary endpoints included serum FT and SHBG. SHBG, FT, and PSA were assessed at, Days 1, 15, 30, 60, and 90 days. Results At enrollment (Day 1) values (n = 9) observed for PSA (38.7 ng/mL ± 52.8), FT (0.89 pg/mL ± 0.70), and SHBG (53.4± 28.6 nmol/L). Data were available from 7 subjects with at least one on-study assessment for FT and SHBG. By Day 15, 75% (3/7) and by Day 60, 100% (4/4) of patients had a ≥50% reduction in PSA. Mean change in FT, at last observation, was -70.4% ± 16.7%. All subjects demonstrated significant increases in SHBG at day 15 (251 ± 63.1 pmol/L) and end of study (266 ± 73.0 pmol/L), with a mean change at last observation of 429% ± 158%. Although there were no venous thromboembolic events (VTEs) in this study, a separate study of GTx-758 for primary ADT in men with advanced prostate cancer was stopped prematurely due to an increased risk of VTEs, and consequently, this study was halted as well. Conclusions GTx-758 is an oral selective ERα agonist that has demonstrated ability to increase SHBG more than 4-fold and decrease FT in men with CRPC. Coupled with the observation that 4/4 patients respond with a ≥50% reduction in PSA at day 30, these results suggest that progression of disease, and the need for increasingly toxic therapies, may be delayed in this population. Significantly lower doses of GTx-758 (100 – 600mg) have also been shown to increase SHBG with a more favorable safety profile in previous Phase I and II GTx-758 studies. Lower doses of GTx-758 are being evaluated in an ongoing Phase II trial in men with CRPC. Disclosure M.S. Steiner: CEO of GTx and own stock, R.P. Taylor: employee of GTx, Inc. and own stock in GTx, Inc., R.H. Getzenberg: employee of GTx, Inc., M.A. Johnston: employee of GTx and own stock, M. Hancock: employee of GTx, Inc. and own stock in GTx, Inc., J.T. Dalton: employee of GTx, Inc. and own stock in GTx, Inc.