18P - First stage of an on-going phase 2, open label, international, randomized, parallel design study investigating efficacy + safety of GTx-024 for adv...

Date 04 May 2017
Event IMPAKT 2017
Session Welcome reception and Poster Walk
Topics Cytotoxic agents
Breast Cancer
Therapy
Biological therapy
Presenter Beth Overmoyer
Citation Annals of Oncology (2017) 28 (suppl_1): i7-i8. 10.1093/annonc/mdx137
Authors B. Overmoyer1, H.S. Rugo2, S. Johnston3, J.A. O'Shaughnessy4, C. Palmieri5, L.S. Schwartzberg6, R.P. Taylor7, D.C. Young7, M.A. Johnston7
  • 1Medical Oncology, Dana Farber Cancer Institute, 02215 - Boston/US
  • 2Comprehensive Cancer Center, UCSF, San Francisco/US
  • 3Breast, Lung & Medical Oncology Services Cbu, Royal Marsden NHS Foundation Trust, London/GB
  • 4Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas/US
  • 5Molecular And Clinical Cancer Medicine, The University of Liverpool, Liverpool/GB
  • 6Hematology/oncology, The West Clinic, Memphis/US
  • 7Scientific Affairs, GTx Inc., 38103 - Memphis/US

Abstract

Body

Background: The androgen receptor (AR) is the most highly expressed steroid receptor in BC, present in >95% estrogen receptor positive (ER+) and 10-50% of ER negative disease. Androgens have been utilized for the treatment of BC; however, their clinical use is limited because of virilizing side effects. GTx-024, a non-steroidal, tissue-selective, AR modulator (SARM), offers a targeted approach of AR activation in ER+/AR+ BC without virilization or estrogenic effects.

Methods: Post-menopausal patients (pts) are randomized to receive GTx-024, 9 mg or 18 mg orally (PO) daily. Therapy is continued until disease progression (PD). Response to prior endocrine therapy is required (no limit on number of regimens), either ≥3 y adjuvant or ≥6 m for MBC; 1 chemotherapy regimen is allowed for MBC. Measurable or bone-only disease is allowed; stable CNS disease permitted. Primary endpoint is clinical benefit (CB) at 24 weeks (wk) in each arm defined as complete response (CR), partial response (PR), or stable disease (SD) per modified RECIST 1.1. Secondary endpoints: objective response rate, progression free survival, time to progression, duration of response, and overall survival. A Simon two-stage design is used. The trial will test for a low CBR of <10% versus a CBR ≥30% among 88 evaluable (EV) pts defined as AR+ by central review. There is no intent to statistically compare the 2 dose arms, rather to determine which doses achieve an acceptable CB. In the 1st stage, if <3/18 pt have CB at 24 wk, the study is stopped. If >3 pt achieve CB, the study proceeds to a total of 118 pts.

Results: The 1st stage of each arm is fully enrolled, and well-tolerated, with 18 pts (9 mg) and 15 pts (18 mg) having either completed a 24 wk evaluation or discontinuing due to other reasons. In the 9 mg arm, of the 10 pts to date that have demonstrated CB at 24 wks, 5 were in the EV subset of the 1st stage (5/18, 28% CBR), one of which was a PR. In the 18 mg arm, of the 6 pts to date that have demonstrated CB at 24 wks, 4 were in the EV subset of the 1st stage (4/15, 27% CBR), one of which was a PR.

Conclusion: Both arms of the study have exceeded the pre-determined threshold in stage 1, progressing to enrollment in stage 2.

Clinical trial identification

NCT02463032

Legal entity responsible for the study

GTx Inc.

Funding

GTx Inc.

Disclosure

B. Overmoyer: Member of GTx Inc. Advisory Board. H.S. Rugo: UCSF PI of a GTX sponsored study in trial negative breast cancer. Not received personal funding from GTX. No potential CI for this abstract. S. Johnston: Honorarium for Consultancy/Advisory work for GTx Inc. J.A. O\'Shaughnessy: Received honoraria from GTX for advisory committee role. C. Palmieri: Member of a GTx ad board and received a grant as part of EMERALD study. L.S. Schwartzberg: GTx Inc. investigator/advisory board member and owner of GTx Inc. stock. R.P. Taylor, D.C. Young, M.A. Johnston: GTx Inc. employee and owner of GTx Inc. stock and stock options.