Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session 2

2549 - Phase 1 Dose Escalation Study of a Selective Androgen Receptor Modulator RAD140 in Estrogen Receptor Positive (ER+), HER2 Negative (HER2-) Breast Cancer (BC)

Date

29 Sep 2019

Session

Poster Display session 2

Topics

Tumour Site

Breast Cancer

Presenters

Erika Hamilton

Citation

Annals of Oncology (2019) 30 (suppl_5): v104-v142. 10.1093/annonc/mdz242

Authors

E. Hamilton1, N. Vidula2, C. Ma3, P. LoRusso4, R.G. Bagley5, Z. Yu6, M. Annett7, A. Weitzman5, M.G. Conlan5, A. Weise8

Author affiliations

  • 1 Drug Development Unit, Sarah Cannon Research Institute-Cancer Centre, 37203 - Nashville/US
  • 2 Medicine, Massachusetts General Hospital, 02114 - Boston/US
  • 3 Medicine, Washington University School of Medicine, 63110 - Saint Louis/US
  • 4 Internal Medicine: Medical Oncology, Yale Cancer Center, 06519 - New Haven/US
  • 5 Clinical Development - Oncology, Radius Health, Inc., 02451 - Waltham/US
  • 6 Research & Development, Radius Health, Inc., 02451 - Waltham/US
  • 7 Biostatistics, Radius Health, Inc., 02451 - Waltham/US
  • 8 Oncology, Barbara Ann Karmanos Cancer Center, 48201 - Detroit/US

Resources

Login to get immediate access to this content.

If you do not have an ESMO account, please create one for free.

Abstract 2549

Background

The androgen receptor (AR) is expressed in ∼ 90% of ER+ BC. Androgen-based therapies have had response rates up to 20-25%, but are not in common use due to poor tissue selectivity, potential aromatization to estrogen, and emergence of ER-targeted agents. RAD140 is an oral nonsteroidal selective AR modulator (SARM) with tissue-selective AR agonist activity in BC cells but attenuated activity in other androgen-responsive tissues. RAD140 inhibited the growth of multiple in vitro and in vivo AR+/ER+ BC models.

Methods

This is a phase 1 study of RAD140 with a 3 + 3 design. The primary objective is safety and to determine the maximum tolerated dose (MTD); secondary objectives are pharmacokinetics and antitumor activity. Key eligibility criteria are: ER+/HER2- and inoperable/metastatic BC (mBC), post-menopausal, and ineligible for standard therapy. AR status is by immunohistochemistry (IHC). Sex hormone-binding globulin (SHBG) and serum prostate specific antigen (PSA) are used to assess AR-engagement.

Results

Dose escalation (n = 16 patients, pts) has been completed. Median age = 58 years, 88% visceral disease, and 94% AR+ by IHC. Median number of prior lines of therapy for mBC = 5; prior fulvestrant 88%, aromatase inhibitor (i) 100%, CDK4/6i 94%, mTORi/PI3Ki 50%, chemotherapy 94%. Dose levels were 50 mg (n = 6), 100 mg (n = 7), and 150 mg (n = 3) QD. Median time on treatment = 8 (range <1-25) wk. The most frequent (>30%) adverse events were elevated ALT/AST, decreased weight/appetite, and constipation. Dose-limiting toxicities (all grade 3 and reversible) were hypophosphatemia (n = 2; 150 mg) and elevated ALT/AST (n = 2; 50 and 100 mg). No drug-related deaths occurred. There was 1 partial response (PR, 100 mg) and 2 pts with stable disease ≥12 wk. The time to PR was 15.9 wk and the duration was 8.6+ wk. SHBG decreased in 12/12 pts and PSA increased in 10/14 pts, most notably in the pt with PR who remains on treatment at 7 mo.

Conclusions

The provisional MTD for RAD140 is 100 mg QD. RAD140 is a novel oral AR-targeted agent for treatment of ER+ mBC with an acceptable safety profile and preliminary evidence of target engagement and antitumor activity. NCT03088527.

Clinical trial identification

NCT03088527.

Editorial acknowledgement

Legal entity responsible for the study

Radius Health, Inc.

Funding

Radius Health, Inc.

Disclosure

E. Hamilton: Advisory / Consultancy: Flatiron Health; Travel / Accommodation / Expenses: Amgen; Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Bayer; Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Clovis Oncology; Research grant / Funding (institution), Travel / Accommodation / Expenses: Eisai; Travel / Accommodation / Expenses: EMD Serono; Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Research grant / Funding (institution), Travel / Accommodation / Expenses: Genentech/Roche; Travel / Accommodation / Expenses: Genzyme; Travel / Accommodation / Expenses: Helsinn Therapeutics; Travel / Accommodation / Expenses: HERON; Travel / Accommodation / Expenses: Lexicon; Research grant / Funding (institution), Travel / Accommodation / Expenses: Medivation; Travel / Accommodation / Expenses: Merck; Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Sysmex; Research grant / Funding (institution), Travel / Accommodation / Expenses: Tesaro. N. Vidula: Research grant / Funding (institution): Radius Health; Research grant / Funding (institution): Daewha; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Pfizer. C. Ma: Research grant / Funding (self): Eisai; Research grant / Funding (self): Puma; Advisory / Consultancy, Research grant / Funding (self): Pfizer; Advisory / Consultancy: Lilly; Advisory / Consultancy: Syndex; Advisory / Consultancy: Seattle Genetics. R.G. Bagley: Shareholder / Stockholder / Stock options, Full / Part-time employment: Radius Health. Z. Yu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Radius Health. M. Annett: Shareholder / Stockholder / Stock options, Full / Part-time employment: Radius Health. A. Weitzman: Shareholder / Stockholder / Stock options, Full / Part-time employment: Radius Health. M.G. Conlan: Shareholder / Stockholder / Stock options, Full / Part-time employment: Radius Health. A. Weise: Speaker Bureau / Expert testimony: Array BioPharma. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.