Abstract OT2-17-01: Randomized, multicenter, international phase 3 ARTEST study to evaluate the efficacy and safety of enobosarm versus active control for the treatment of AR+ ER+ HER2- metastatic breast cancer in patients who progressed on a nonsteroidal aromatase inhibitor, fulvestrant and CDK 4/6 inhibitor

Abstract

Abstract Targeting the androgen receptor (AR) may be the next important endocrine therapy for women with advanced breast cancer. AR is the most abundantly expressed steroid receptor in breast cancer and has been demonstrated to be a tumor suppressor when activated. Enobosarm is an oral selective nonsteroidal agonist that activates the AR in breast cancer. Enobosarm has an extensive clinical experience in 25 clinical trials and 1,450 dosed subjects including in breast cancer where three Phase 2 studies have been conducted two of which were in women (158 subjects) who had AR+/ER+/HER2- metastatic breast cancer (MBC).The larger Phase 2 clinical trial (G200802) evaluated 9mg and 18mg enobosarm daily oral dosing in 136 women with ER+/HER2- MBC who previously responded to endocrine treatment. Patients were heavily pretreated having progressed on an average of 3 endocrine treatments and 90% had prior chemotherapy. Enobosarm showed efficacy activity in the overall study with a clinical benefit rate at 6 months of 32% (95% CI: 19.5%,46.7%) for the 9 mg and 29% (95% CI: 17.1%,43.1%) for the 18 mg evaluable cohorts. Quality of life assessments showed significant improvement from baseline for both enobosarm cohorts (p=0.002). Enobosarm was well tolerated at both doses. In a post-hoc analysis in all patients (9mg and 18mg) with known AR status and measurable disease (n=84), AR expression in breast. cancer tissue (%AR nuclei staining) correlated with efficacy outcomes. When comparing AR nuclei staining ≥40% (n=47) compared to patients with an AR nuclei staining <40% (n=37): 1) Clinical benefit rate at 6 months was 52% for AR ≥40% and 14% for AR <40% (p<0.0004); 2) Overall response rate (ORR) was 34% for AR ≥40% and 2.7% for AR <40% (p<0.0003; 3) Radiographic was 5.47 months for AR ≥40% and 2.72 months for AR <40% (p<0.001). The ARTEST trial is a Phase 3 multicenter, international randomized, open-label, two treatment arm, efficacy and safety study. Approximately, 210 subjects with AR+ ER+ HER2- MBC and with AR nuclei staining ≥40% will be randomized 1:1 to either enobosarm 9mg oral daily dose or an active comparator (either exemestane ± everolimus or selective estrogen receptor modulator; physician’s choice). Subjects will be treated until disease progression is observed or an unacceptable adverse event is observed. The primary endpoint of the study is imaging based progression free survival as measured by RECIST 1.1. The secondary objectives/endpoints on this study include the ORR, duration of response, overall survival, and change from baseline in Short Physical Performance Battery (SPPB). The study is planned to begin enrollment in Q3 2021. Citation Format: Adam Brufsky, Hannah Linden, Hope Rugo, Charles Vogel, Joyce A O'Shaughnessy, Robert H Getzenberg, K. Gary Barnette, Domingo Rodriguez, Mitchell S Steiner, Erica Mayer. Randomized, multicenter, international phase 3 ARTEST study to evaluate the efficacy and safety of enobosarm versus active control for the treatment of AR+ ER+ HER2- metastatic breast cancer in patients who progressed on a nonsteroidal aromatase inhibitor, fulvestrant and CDK 4/6 inhibitor [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-17-01.