ELECTRA: An open-label, multicenter, phase 1b/2 study of elacestrant in combination with abemaciclib in patients with brain metastasis from ER+/HER2− breast cancer.

TPS1155 Background: Endocrine therapy (ET) + cyclin dependent kinase 4/6 inhibitor (CDK4/6i) is the mainstay for the management of ER+/HER2- mBC as 1 st -line therapy. However, tumors eventually develop resistance to ET, leading to disease progression. In the EMERALD phase 3 trial, single-agent elacestrant demonstrated a significantly prolonged progression-free survival (PFS) vs SOC ET ( ESR1 m tumors HR 0.55; 95% CI 0.39-0.77; all pts HR 0.70; 95% CI 0.55-0.88) with a manageable safety profile (Bidard 2022), leading to the first oral SERD approved. In a subgroup analysis in patients with ESR1m tumors who had received prior ET+CDK4/6i ≥12 months, the median PFS for elacestrant was of 8.6 months vs 1.9 months with SOC ET (HR=0.41; 95% CI, 0.26-0.63) [Bardia CCR 2024]. Currently, there are no approved systemic treatments for patients with ER+/HER2- breast cancer who have brain metastasis. ELECTRA (NCT05386108) is an open-label phase 1b/2, multicenter study evaluating elacestrant in combination with abemaciclib. The phase 1b portion of ELECTRA evaluated the combination of elacestrant with abemaciclib in patients with ER+/HER2- mBC regardless of metastatic site and ESR1 status. The recommended phase 2 dose (RP2D) of the combination was determined to be elacestrant 345 mg QD with abemaciclib 150 mg BID (Ibrahim ASCO 2024). The phase 2 portion of ELECTRA is ongoing to further characterize efficacy and safety of this combination in patients with brain metastases from ER+/HER2- breast cancer, as both compounds cross the blood-brain barrier (Conlan, 2020; Tolaney, 2020). Methods: Phase 2 eligibility includes patients with ER+/HER2- locally advanced or metastatic breast cancer and measurable brain metastasis (≥ 1 active and measurable brain metastasis per RECIST v1.1). Patients must have received prior therapy in the metastatic setting, including ≥ 1 endocrine therapy, ≤ 2 chemotherapy regimens, and 0-2 prior CDK4/6i (excluding abemaciclib). The phase 2 primary objective is ORR per RECIST v1.1; secondary objectives include intracranial response rate, DoR, CBR, PFS, OS, PK, and quality of life. The phase 2 portion of ELECTRA is actively recruiting patients worldwide. Clinical trial information: NCT05386108 .