Annals of Oncology 25 (Supplement 4): iv255–iv279, 2014 doi:10.1093/annonc/mdu336.5
757O
GALETERONE IN 4 PATIENT POPULATIONS OF MEN WITH CRPC: RESULTS FROM ARMOR2
M. Taplin1, K.N. Chi2, F. Chu3, J. Cochran4, W.J. Edenfield5, M. 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 1 Medical Oncolgy, Dana-Farber Cancer Institution, Boston, MA, USA 2 Oncology, BC Cancer Agency - Vancouver Centre, Vancouver, BC, CANADA 3 Urology, San Bernardino Urological Associates, San Bernardino, CA, USA 4 Clinical Research, Urology Clinics of North Texas, Dallas, TX, USA 5 Clinical Research Unit/ITOR, Greenville Health System Cancer Institute, Greenville, SC, USA 6 Medicine, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medical Center, Baltimore, MD, USA 7 Medical Oncology, Sunnybrook Odette Cancer Center, Toronto, ON, CANADA 8 Oncology, Karmanos Cancer Institute, Detroit, MI, USA 9 School of Medicine, University of Maryland, Baltimore, MD, USA 10 Dept. of Thoracic Oncology, Lynn Cancer Institute, Boca Raton, FL, USA 11 Urology, Carolina Clinical Trials, Concord, NC, USA 12 Clinical Research, Omaha (Urology Cancer Center PC), Omaha, NE, USA 13 Oncology, Roswell Park Medical Centre, Buffalo, NY, USA 14 Institute of Urologic Oncology, UCLA David Geffen School of Medicine, Los Angeles, CA, USA 15 Department of Medicine: Section of Hematology & Medical Oncology and Department of Urology, Tulane Cancer Center, New Orleans, LA, USA 16 Urology, Carolina Urologic Research Center, Myrtle Beach, SC, USA 17 Clinical Research, Tokai Pharmaceuticals, Cambridge, MA, USA 18 Genitourinary Medical Oncology, University of Washington Medical Center, Seattle, WA, USA 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. Table: 757O Maximum Response w/in 12 Weeks 2550 mg Dose
N*
PSA30 N (%)
PSA50 N (%)
Best Overall Response Per RECIST PR/SD (N**)
M0 TN M1 TN Abi-R Enza-R
14 36 12 2
10 (71) 32 (89) 2 (17) 0 (0)
9 (64) 29 (81) 0 (0) 0 (0)
0/2 (5) 1/14 (15) 0/5 (7) 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.
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abstracts
genitourinary tumours, prostate
