757O - Galeterone in 4 patient populations of men with CRPC: Results from ARMOR2

Date 29 September 2014
Event ESMO 2014
Session Genitourinary tumours, prostate 2
Topics Drug Development
Prostate Cancer
Translational Research
Presenter Mary-Ellen Taplin
Citation Annals of Oncology (2014) 25 (suppl_4): iv255-iv279. 10.1093/annonc/mdu336
Authors M. Taplin1, K.N. Chi2, F. Chu3, J. Cochran4, W.J. Edenfield5, M.A. Eisenberger6, U. Emmenegger7, E.I. Heath8, A. Hussain9, A. Koletsky10, D. Lipsitz11, L. Nordquist12, R. Pili13, M. Rettig14, O. Sartor15, N.D. Shore16, R. Dhillon17, J. Roberts17, B. Montgomery18
  • 1Medical Oncolgy, Dana-Farber Cancer Institution, 02115 - Boston/US
  • 2Oncology, BC Cancer Agency - Vancouver Centre, V5Z4E6 - Vancouver/CA
  • 3Urology, San Bernardino Urological Associates, 92404 - San Bernardino/US
  • 4Clinica Research, Urology Clinics of North Texas, Dallas/US
  • 5Clinical Research Unit/itor, Greenville Health System Cancer Institute, 29605 - Greenville/US
  • 6Medicine, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medical Center, 21231 - Baltimore/US
  • 7Medical Oncology, Sunnybrook Odette Cancer Center, CA-M4N 3M5 - Toronto/CA
  • 8Oncology, Karmanos Cancer Institute, 48201 - Detroit/US
  • 9School Of Medicine, University of Maryland, 21201 - Baltimore/US
  • 10Dept. Of Thoracic Oncology, Lynn Cancer Institute, Boca Raton/US
  • 11Urology, Carolina Clinical Trials, 28025 - Concord/US
  • 12Clinical Research, Omaha (Urology Cancer Center PC), Omaha/US
  • 13Oncology, Roswell Park Medical Centre, Buffalo/US
  • 14Institute Of Urologic Oncology, UCLA David Geffen School of Medicine, 90095-7384 - Los Angeles/US
  • 15Department Of Medicine: Section Of Hematology & Medical Oncology And Department Of Urology, Tulane Cancer Center, 70112 - New Orleans/US
  • 16Urology, Carolina Urologic Research Center, Myrtle Beach/US
  • 17Clinical Research, Tokai Pharmaceuticals, 02142 - Cambridge/US
  • 18Genitourinary Medical Oncology, University of Washington Medical Center, 98185 - Seattle/US

Abstract

Aim

Galeterone is an oral small molecule that disrupts androgen receptor (AR) signaling via multi-targeted mechanisms of action (MOA): (1) selective inhibition of CYP17 lyase; (2) competitive antagonism of androgen binding to AR; and (3) degradation of AR protein. Galeterone is a single molecule with potential advantage beyond approved CYP17 and AR inhibitors in that it combines AR degradation with AR antagonism and CYP17 suppression and has no steroid requirement.

Methods

ARMOR2 (NCT#01709734) is a two part, Ph 2 study designed to confirm dose of reformulated galeterone (1700 mg-3400 mg QD for 12 wks) (Part 1) and assess safety and efficacy of 2550 mg QD for 12 wks (Part 2). As of April 18, 2014, 4 cohorts of CRPC patients (pts) have been treated at 2550 mg: non-metastatic treatment (tx) naive (TN) (M0 TN, n = 18), metastatic tx naive (M1 TN, n = 36), abiraterone refractory (Abi-R n = 21) and enzalutamide refractory (Enza-R, n = 2). Additional arms have been added.

Results

PSA response was seen at 2550 mg in all tx groups. In 36 M1 TN pts, PSA declines of 30% and 50% (PSA30 and PSA50) were acheived in 89% and 81% of patients respectively. The M1 TN pts had best overall response per RECIST with 14/15 with stable disease (SD) and 1/15 with partial response (PR) in evaluable pts at 3 mos. Safety: galeterone was well tolerated at all doses (parts 1 and 2) with gr 1 or 2 treatment related AEs occurring in 57% of pts; the most frequent were nausea (34%), fatigue (23%) and pruritis (22%). There was a total of 19% gr 3 and 2% gr 4 related AEs. There was no mineralcorticoid excess (ME) or seizures.

Maximum Response w/in 12 Weeks
2550 mg Dose N* PSA30 N (%) PSA50 N (%) Best Overall Response Per RECIST PR/SD (N**)
M0 TN 14 10 (71) 9 (64) 0/2 (5)
M1 TN 36 32 (89) 29 (81) 1/14 (15)
Abi-R 12 2 (17) 0 (0) 0/5 (7)
Enza-R 2 0 (0) 0 (0) NA

Conclusions

Galeterone has shown signifiant biochemical and clinical activity and is well tolerated with no ME or seizures. The study will continue to explore safety and efficacy of galeterone in pts with progression following abiraterone and/or enzalutamide, chemotherapy and in additional arms. Also, data on CTCs will be presented and correlated with outcomes.

Disclosure

M. Taplin: Advisory Boards: Medivation, Janssen, Dendron, Bayer, Tokai (individually < $10,000 each) Research Funding: Genentech, Medivation, Bayer, Janssen; K.N. Chi. J. Cochran, W.J. Edenfield, U. Emmenegger, E.I. Heath, A. Koletsky, D. Lipsitz, R. Pili, O. Sartor and N.D. Shore: Investigator for the Tokai Pharmaceuticals clinical study TOK-200-10 (ARMOR2); F. Chu, M. Eisenberger, A. Hussain,L. Nordquist and M. Rettig: Grant support from TOKAI for participation in the ARMOR 2 study; R. Dhillon and J. Roberts: Employee of study sponsor - Tokai Pharmaceuticals; B. Montgomery: Grant support from TOKAI for participation in the ARMOR 2 study.