Abstract PO2-27-03: Clinical Results of Subjects Remaining in the Phase 3 ARTEST Study Enobosarm Therapy in AR+ER+HER2- Metastatic Breast Cancer with 3 or Greater Prior Lines of Therapy

Abstract Background: Targeting the androgen receptor (AR) with an oral selective AR agonist, enobosarm, is a novel approach to overcome ER and CDK4/6 inhibitor resistance to suppress AR+ER+HER2- metastatic breast cancer (mBC). Preclinical studies in CDK4/6 inhibitor and estrogen blocking agent resistant PDX mBC models demonstrated that enobosarm alone suppressed tumor growth. In a small subgroup analysis of patients with ER+HER2- mBC who progressed on estrogen blocking agent and a CDK 4/6 inhibitor from the Phase 2 802 study, enobosarm treatment resulted in a best overall response rate of 30% (2 CRs and 1 PR) and a 6-month clinical benefit rate (CBR) of 50%. Methods: The clinical activity of enobosarm 9mg alone was evaluated compared to standard of care (SOC) in the Phase 3 ARTEST, open-label, randomized, multicenter study in AR+ER+HER2-mBC who have progressed on 2 or greater lines of prior therapies, including estrogen blocking agents and CDK4/6 inhibitors. The study was discontinued for administrative reasons not related to efficacy or safety. Results: At the time study was discontinued, 34 patients with confirmed AR positivity were randomized to either enobosarm (n=16) or SOC control (n=18). SOC control treatment group received an average of 2.6 (range 1-5) and enobosarm 9mg monotherapy an average of 2.9 (range 1-5) prior lines of treatment. On average, enobosarm or the SOC control was given in the 4th line treatment for AR+ER+HER2- metastatic breast cancer. In the evaluable population, two partial responses were observed in the enobosarm treatment arm versus no responses in the SOC control arm. In patients with ≤3 lines of prior endocrine therapy, the best objective response rate (ORR) was 18.8% for enobosarm and 0% for control. In patients with ≤3 lines of prior endocrine therapy with ≤1 prior treatment with CDK 4/6 inhibitor, best ORR was 33% in the enobosarm group versus no responses in the SOC control (Table 1). CBR on day 180 was 33.3% (4/12) in the enobosarm group vs 0% (0/11) in the control group. Enobosarm treatment was well tolerated without masculinizing adverse events and no increases in hematocrit changes. Conclusions: Activity of enobosarm in this heavily pretreated patient population is encouraging and supports further clinical investigation. The Phase 3 ENABLAR-2 study is underway to further evaluate enobosarm alone or in combination with abemaciclib for the second-line treatment of AR+ER+HER2- metastatic breast cancer in patients who have received a prior estrogen blocking agent and a CDK 4/6 inhibitor. Clinical trial information: NCT04869943. Research Sponsor: Veru Inc. Table 1. Responses in patients with enobosarm versus SOC treatment. Citation Format: Kristine Rinn, Elisa Krill Jackson, Gary Barnette, Domingo Rodriguez, Itay Shalev, Mitchell Steiner, Joyce O'Shaughnessy, Hope Rugo, Adam Brufsky. Clinical Results of Subjects Remaining in the Phase 3 ARTEST Study Enobosarm Therapy in AR+ER+HER2- Metastatic Breast Cancer with 3 or Greater Prior Lines of Therapy abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-27-03.