Abstract P2-10-18: A study to evaluate the safety and efficacy of vosilasarm (EP0062), an oral SARM, as monotherapy and in combination with standard of care regimens in patients with relapsed locally advanced or metastatic AR+/HER2-/ER+ breast cancer

Abstract Abstract: AR activation exerts potent antitumor activity across a number of ER+ /AR+ breast tumors, including those resistant to standard-of-care endocrine therapy and CDK4/6 inhibitors (Hickey et al, Nature Medicine 2021 27: 310-320). Agonist activation of AR alters the genomic distribution of ER and essential co-activators resulting in repression of ER-regulated cell cycle genes and upregulation of AR target genes, including known tumor suppressors. The clinical activity of SARMs has now been confirmed in several studies (LoRusso et al. Clinical Breast Cancer 2022 22;1 67-77, Palmieri et al Lancet Oncol 2024 25: 317-325). Vosilasarm (EP0062) is an oral, non-steroidal, Selective Androgen Receptor Modulator (SARM) in development for the treatment of AR+/HER2-/ER+ locally advanced or metastatic breast cancer. This ongoing study (NCT05573126) is evaluating the safety and initial efficacy of vosilasarm in patients with AR+/HER2–/ER+ locally advanced or metastatic breast cancer as monotherapy and in combination. Module A, which is ongoing, is comprised of dose optimisation cohorts in a 3+3 design, to investigate safety, tolerability, PK and PD and to define the optimum dose for planned combination expansions. 20 patients have been included to-date across 4 dose cohorts. In Module B, vosilasarm is being evaluated in combination with standard-of-care therapies in patients with relapsed AR+/HER2-/ER+ locally advanced or metastatic breast cancer to confirm safety and explore efficacy. Approximately 20 patients will be included initially across 2 cohorts: Cohort 1. Vosilasarm + elacestrant in patients with AR+/HER2-/ER+/ESR1mut + advanced/metastatic breast cancer that has progressed on one or two prior lines of endocrine therapy, including prior CDK4/6 inhibitor Cohort 2. Vosilasarm + everolimus + exemestane in patients with AR+/HER2-/ER+ advanced/metastatic breast cancer that has progressed on a prior endocrine therapy + CDK4/6 inhibitor Key inclusion criteria are as follows: Post-menopausal women, ≥18 years ECOG performance status of 0 to 1 Locally advanced or metastatic breast cancer ER+, HER2- as per ASCO CAP guidelines AR+, as defined as ≥ 10% AR nuclei staining by IHC Endocrine-therapy-sensitive breast cancer defined as: a) greater than 2 years of adjuvant endocrine therapy prior to development of advanced or metastatic disease, OR b) previous response (without disease progression for at least 6 months) to one of the following treatments in the advanced/metastatic setting: SERD +/- CDK 4/6 inhibitor, AI +/- CDK 4/6 inhibitor Measurable disease defined by RECIST version 1.1, or bone-only disease The vosilasarm dose will be selected from the findings of the dose finding/optimisation cohorts in Module A. Combination agents will be initiated at approved doses. An initial 3-6 patients will be enrolled in order to assess safety and tolerability of vosilasarm + the combination agent and to establish the appropriate combination dose for vosilasarm, with subsequent expansion to 10 patients per cohort. Cohorts may be expanded to 25 patients dependent on safety and efficacy findings. Endpoints include incidence and severity of AEs and SAEs, plasma PK parameters, Clinical Benefit Rate (CBR, complete response, partial response, or stable disease) at 24 weeks, ORR, duration of response, PFS, OS and quality of life. Planned blood and tissue biomarkers in this study include prostate-specific antigen (PSA), cancer antigen (CA) 15-3, and circulating tumour DNA (ctDNA). Recruitment of combination cohorts will be initiated in Q4 2024. Citation Format: Joyce O’Shaughnessy, Erika Hamilton, Noelia Martinez, Elisa Fontana, Rodrigo Sanchez-Bayona, Patricia LoRusso, Carlo Palmieri, Anne Armstrong, Valentina Boni, Meritxell Bellet Ezquerra, Aidan Doherty, Mags McDonagh, Sital Patel, Geoff Fisher, Sue Brook, Hendrik-Tobias Arkenau, Hyo Han. A study to evaluate the safety and efficacy of vosilasarm (EP0062), an oral SARM, as monotherapy and in combination with standard of care regimens in patients with relapsed locally advanced or metastatic AR+/HER2-/ER+ breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-10-18.