964TiP - ARN-509 in men with metastatic castration-resistant prostate cancer (CRPC)

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Clinical Research
Prostate Cancer
Basic Scientific Principles
Presenter Dana E. Rathkopf
Authors D.E. Rathkopf1, E.S. Antonarakis2, N.D. Shore3, R. Tutrone4, J. Alumkal5, C.J. Ryan6, M. Saleh7, R. Hauke8, E. Chow-Maneval9, H.I. Scher1
  • 1Medicine, Memorial Sloan-Kettering Cancer Center, New York/US
  • 2Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore/US
  • 3Urology, Carolina Urologic Research Center, Myrtle Beach/US
  • 4Urology, Chesapeake Urology Research Associates, Baltimore/US
  • 5Medicine, Oregon Health & Science University Knight Cancer Institute, Portland/US
  • 6University of California, San Francisco, 94115 - San Francisco/US
  • 7Medicine, Georgia Cancer Specialists, Atlanta/US
  • 8Medicine, Nebraska Cancer Specialists, Omaha/US
  • 9Clinical Development, Aragon Pharmaceuticals, San Diego/US



ARN-509 is a novel second-generation anti-androgen that binds directly to the ligand-binding domain of the androgen receptor, impairing nuclear translocation and DNA binding. The Phase II portion of a multicenter Phase I/II study is evaluating the activity of ARN-509 in 3 distinct patient populations of men with CRPC: 1) non-metastatic treatment-naïve CRPC; 2) mCRPC treatment-naïve (tx-naïve); and 3) mCRPC abiraterone acetate pre-treated (AA). Preliminary results for the 2 cohorts of patients with metastatic CRPC are presented here.


All patients had metastatic CRPC with progressive disease based on rising PSA and/or imaging. No prior chemotherapy for metastatic prostate cancer was allowed. Patients on the AA pre-treated cohort had to have been treated with AA for at least 6 months. All patients received ARN-509 at the recommended Phase II dose of 240 mg/day (Rathkopf et al, GU ASCO 2012). The primary endpoint was PSA response rate at 12 weeks according to the Prostate Cancer Working Group 2 Criteria in each of the treatment groups. Secondary endpoints included safety, time to PSA progression and objective response rates. PSA assessments were collected every 4 weeks and tumor imaging was performed every 16 weeks.


To date, 32 patients have been enrolled: 25 on the tx-naïve and 7 on the post-AA cohorts, respectively. The combined median age was 67 (range 51-91) and at baseline, patients presented with ECOG performance status 0 (55%), Gleason Score 8-10 (54%), and median PSA of 14.7 (tx-naïve) and 69.6 (post-AA) ng/mL. All patients received prior treatment with a LHRH analog with or without a first-generation anti-androgen. At a median treatment duration of 16 weeks, 4 patients discontinued the study due to disease progression, 2 in each cohort. The most common treatment-related adverse events (AE) were abdominal pain (36%), diarrhea (19%), nausea (16%) and fatigue (10%). There was only 1 treatment-related Grade 3 AE of abdominal pain. At 12 weeks, the PSA response was 91% (tx-naïve) and 60% (post-AA), respectively.


In men with CRPC, ARN-509 is safe and well tolerated with promising preliminary activity in metastatic, chemo-naïve patients both before and after treatment with abiraterone.


E. Chow-Maneval: Dr. Chow Maneval is an employee of Aragon and holds stock in the company.

All other authors have declared no conflicts of interest.