J. O'Shaughnessy (Dallas, United States of America)

Texas Oncology - Baylor Sammons Cancer Center

Author Of 1 Presentation

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100P - Efficacy of Enobosarm, a selective androgen receptor (AR) targeting agent, in patients with metastatic AR+/ER+ breast cancer resistant to estrogen receptor targeted agents and CDK 4/6 inhibitor in a Phase 2 clinical study

Abstract

Background

CDK 4/6 inhibitors (CDK4/6i) in combination with an ER targeted agent are the standard of care in in the treatment of metastatic ER+ breast cancer (MBC). Despite the significant increase in progression free survival seen with this combination, all patients eventually progress and therefore, there is a need for additional therapeutic options. The AR is expressed in up to 90% of ER+ breast cancer where it acts as a tumor suppressor. Enobosarm is a selective AR activating agent that does not cause virilization, and has positive clinical attributes such as promotion of bone strength and improvement of physical function. We report the clinical activity of enobosarm post CDK4/6i in women with AR+/ER MBC.

Methods

In study G200802, women with heavily pretreated AR+/ER+ MBC were randomized to receive either 9 mg (n=72) or 18 mg (n=64) of oral daily enobosarm. The safety and clear clinical activity of enobosarm in this study has previously been reported (Palmieri et al., 2020). In this analysis, the antitumor activity of targeting AR in women previously treated with and progressing on a CDK 4/6i in study G200802 was examined.

Results

There were 10 evaluable patients with measurable metastatic AR+/ER+ MBC who had progressed following treatment with a CDK 4/6i (palbociclib). Enobosarm, dosed at either 9mg or 18 mg oral daily, resulted in a clinical benefit rate of 60%, and the best objective tumor response was 33% including 2 CRs and 1 PR. The overall mean radiographic PFS in the 9 mg cohort was 10.6 months and the median was 5.2 months. Enobosarm was well tolerated.

Conclusions

We report clinical activity of enobosarm in patients with AR+/ER+ MBC with prior disease progression on ER directed therapy plus palbociclib. At the 9 mg dose, which has been selected for the phase III study, the mean rPFS was 10.6 months. These data provide support for exploring the potential clinical benefit of targeting AR with enobosarm in MBC that has progressed on a CDK4/6 inhibitor. The phase III, ARTEST trial will commence in the Q2 2021 in patients with AR+/ER+/HER2- metastatic breast cancer that has progressed on a non-steroidal aromatase inhibitor, fulvestrant and CDK 4/6 inhibitor.

Clinical trial identification

NCT02463032.

Legal entity responsible for the study

GTx performed the study and Veru Inc performed the data analysis.

Funding

GTx funded the clinical trial and Veru Inc supported the data analysis.

Disclosure

C. Vogel, J. O'Shaughnessy, A.M. Brufsky: Advisory/Consultancy: Veru Inc. R.H. Getzenberg: Shareholder/Stockholder/Stock options, Full/Part-time employment: Veru Inc. K.G. Barnette, M. Steiner: Shareholder/Stockholder/Stock options, Full/Part-time employment, Officer/Board of Directors: Veru Inc. All other authors have declared no conflicts of interest.

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