A phase 1/2 study of EP0062 (vosilasarm), a first-in-class oral selective androgen receptor modulator (SARM), in combination with standard-of-care endocrine therapy +/- targeted therapies in patients with advanced or metastatic AR+/ER+/HER2− breast cancer.

Abstract

TPS1151 Background: EP0062 (vosilasarm), a first-in-class, oral, non-steroidal, Selective Androgen Receptor Modulator (SARM) acts as a potent tissue-selective AR agonist, suppressing growth and proliferation of multiple endocrine-sensitive or -resistant AR+/ER+/HER2- breast cancer (BC) cell lines and patient-derived xenograft (PDX) models. Pre-clinically, AR activation--rather than AR suppression--exerts potent antitumor activity in AR+/ER+ breast malignancies, including those resistant to endocrine therapy and CDK4/6 inhibitors. EP0062 has been shown to inhibit the growth of AR+/ER+ BC PDX models as a single agent, and in combination with palbociclib, everolimus or elacestrant. Phase 1 of this study reported promising safety and evidence of clinical benefit with EP0062 monotherapy in advanced AR+/ER+/HER2- BC. The ongoing Phase 2 cohorts described here are the first clinical evaluation of a SARM in combination with various standard of care therapies in patients that have previously received a CDK4/6 inhibitor. Methods: The Phase 2 cohorts will include up to 75 post-menopausal women, ≥ 18 years, ECOG ≤ 1, with locally advanced/metastatic, endocrine-sensitive (> 2 y adjuvant or >6 mo treatment prior to recurrence), AR+/ER+/HER2- BC, that is measurable per RECIST v1.1, or non-measurable with an evaluable bone component. AR positivity is defined as ≥ 10% AR nuclei staining by IHC. Patients may have previously received ≤ 2 lines of endocrine therapy (including CDK4/6 inhibitor), and ≤ 1 line of chemotherapy in the advanced/metastatic setting. Treatment arms are as follows: Arm 1: EP0062 + elacestrant (mandatory ESR1 mutation); Arm 2: EP0062 + exemestane + everolimus; Arm 3: EP0062 + fulvestrant + abemaciclib. A 3+3 safety run-in will confirm the combination dose for each cohort before expansion. Starting EP0062 dose was 10 mg BID. The primary objective is to evaluate safety and tolerability. Secondary objectives are to characterise the PK profile and preliminary efficacy. Biomarkers, including CA15-3, PSA, and molecular genetics are also being evaluated. Exploratory objectives are to evaluate potential biomarkers of efficacy, safety and/or PD activity. The study is currently recruiting across the three treatment arms in USA, UK, and Spain. Clinical trial information: NCT05573126 .