920P - Arn-509 in men with high risk non-metastatic castration-resistant prostate cancer

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Drug Development
Prostate Cancer
Presenter Matthew Smith
Authors M.R. Smith1, E.S. Antonarakis2, C.J. Ryan3, W. Berry4, N.D. Shore5, G. Liu6, J. Alumkal7, C. Higano8, E.C. Maneval9, D.E. Rathkopf10
  • 1Hematology-oncology, Massachusetts General Hospital, 02114 - Boston/US
  • 2Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore/US
  • 3University of California, San Francisco, 94115 - San Francisco/US
  • 4Oncology, Cancer Centers of North Carolina, Raleigh/US
  • 5Urology, Carolina Urologic Research Center, Myrtle Beach/US
  • 6Oncology, University of Wisconsin Carbone Cancer Center, 53792 - Madison/US
  • 7Medicine, Oregon Health & Science University Knight Cancer Institute, Portland/US
  • 8Seattle Cancer Care Alliance, University of Washington, 98109 - Seattle/US
  • 9Clinical Development, Aragon Pharmaceuticals, 92130 - San Diego/US
  • 10Medicine, Memorial Sloan-Kettering Cancer Center, 10128 - New York/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 (high risk non-metastatic CRPC, metastatic treatment-naïve CRPC, and progressive disease after abiraterone acetate). Preliminary results for the cohort of patients with high-risk non-metastatic CRPC are presented here.


All patients had CRPC, no radiographic evidence of metastases (pelvic lymph nodes <3 cm below the iliac bifurcation were allowed), and high risk for disease progression based on PSA value ≥ 8 ng/mL within 3 months of enrollment and/or PSA doubling time ≤ 10 months. Patients received ARN-509 at the recommended Phase II dose of 240 mg/day, previously established in Phase I (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. Secondary endpoints included safety, time to PSA progression and 1-year metastasis-free survival. PSA assessments were collected every 4 weeks and tumor scans were performed every 16 weeks.


Fifty patients were enrolled between November 2011 and May 2012. The median age was 72 years (range 51 to 86) and at baseline, patients presented with ECOG performance status 0 (67%), Gleason Score 8-10 (38%), and median PSA of 11.5 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 8 weeks, only one patient discontinued the study (due to inability to comply with the protocol). The most common adverse events (AE) were fatigue (13%), diarrhea (9%), nausea (6%) and abdominal pain (6%). There were no Grade > 2 AEs and no patients required dose modifications. At 12 weeks, 17/19 patients (89.5%) of patients had a PSA response. The median decrease in PSA from baseline to week 12 was 83.3%.


In men with high-risk non-metastatic CRPC, ARN-509 is safe and well tolerated with promising preliminary activity based on high PSA response rates.


E. Chow-Maneval: As an employee of Aragon Pharmaceuticals, I have stock ownership in Aragon Pharmaceuticals.All other authors have declared no conflicts of interest.