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Poster display session

3902 - EPI-506 (ralaniten acetate), a novel androgen receptor (AR) N-terminal domain (NTD) inhibitor, in men with metastatic castration-resistant prostate cancer (mCRPC): Phase 1 update on safety, tolerability, pharmacokinetics and efficacy

Date

10 Sep 2017

Session

Poster display session

Topics

Clinical Research;  Prostate Cancer

Presenters

Ulka Vaishampayan

Citation

Annals of Oncology (2017) 28 (suppl_5): v269-v294. 10.1093/annonc/mdx370

Authors

U. Vaishampayan1, R.B. Montgomery2, M.S. Gordon3, D.C. Smith4, K. Barber5, A. de Haas-Amatsaleh6, N. Thapar7, C. Chandhasin8, F. Perabo6, K.N. Chi9

Author affiliations

  • 1 Oncology, Karmanos Cancer Institute, 48201-2013 - Detroit/US
  • 2 Genitourinary Medical Oncology, University of Washington, Seattle/US
  • 3 Medical Oncology, HonorHealth Research Institute, Scottsdale/US
  • 4 Medical Oncology, University of Michigan, Ann Arbor/US
  • 5 Clinical Operations, ESSA Pharmaceuticals Corp., 77030 - Houston/US
  • 6 Medical, ESSA Pharmaceuticals Corp., 77030 - Houston/US
  • 7 Clinical Pharmacology, ESSA Pharmaceuticals Corp., 77030 - Houston/US
  • 8 Medical & Scientific Affairs, ESSA Pharmaceuticals Corp., 77030 - Houston/US
  • 9 Experimental Therapeutics, BC Cancer Agency, Vancouver/CA
More

Resources

Abstract 3902

Background

EPI-506 (ralaniten acetate) is being studied in a Phase 1/2 study as a first-in-class transcription inhibitor of the AR NTD.

Methods

Open-label, single-arm, Phase 1/2 study evaluating EPI-506 administered orally. The Phase 1 is a modified 3 + 3 design to establish safety, tolerability, pharmacokinetics (PK), maximum-tolerated-dose (MTD) and the recommended phase 2 dose (RP2D) of EPI-506. Anti-tumor activity is evaluated by PSA and imaging. Inclusion criteria include: mCRPC with progression after > =1 line of hormonal therapy or chemotherapy, failure to treatment with enzalutamide and/or abiraterone.

Results

Twenty-one patients (pts) have been enrolled in the dose escalation phase over 6 dose levels (80 - 2,400 mg). Median age was 72 (range 58-87). Prior treatments included enzalutamide only (N = 9), abiraterone only (N = 3) or both (N = 9). Eight pts also had prior chemotherapy. Twelve pts discontinued due to disease progression and 2 pts due to adverse events (AEs): Grade 4 elevated amylase (probably related; at 640mg) and Grade 4 gastrointestinal bleeding (unrelated). Median exposure was 87 days at cut-off (range 21-418). Most frequently reported treatment emergent AEs were diarrhea (N = 8), nausea (N = 6), and pain in extremities (N = 5). One possibly related Grade 3 AE (AST elevation) was observed at 1280 mg. PK data demonstrate a dose-proportional profile for Cmax and AUC together with a positive food effect above 640 mg. Three of 21 evaluable pts demonstrated PSA declines ranging from 4 – 29%, and one pt with unchanged PSA at doses >1,280 mg. Three pts have had prolonged treatment (median of 286 days; range 219 – not reached), after intrapatient dose escalation. The study is currently enrolling pts with a total dose of 3,600 mg in both a QD and a BID dosing schedule.

Conclusions

EPI-506 is well-tolerated with an acceptable safety profile. PK indicates dose-proportionality. PSA declines and stable disease have been observed at higher dose cohorts in this ongoing study. This study is the first to evaluate targeting the AR NTD, a region critical for transcriptional function of all known AR species.

Clinical trial identification

NCT02606123

Legal entity responsible for the study

ESSA Pharmaceuticals

Funding

ESSA Pharmaceuticals

Disclosure

U. Vaishampayan, M.S. Gordon, D.C. Smith: ESSA Pharmaceuticals Corp. (Research funding) R.B. Montgomery, K.N. Chi: ESSA Pharmaceuticals Corp. (Scientific advisory board; Honoraria received; Research funding). K. Barber, F. Perabo, N. Thapar, C. Chandhasin: ESSA Pharmaceuticals Corp. (Employed, Ownership interest). A. de Haas-Amatsaleh: ESSA Pharmaceuticals Corp. (Consultant).

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