TIP134 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

Background

Endocrine therapy (ET) plus CDK4/6 inhibitor (CDK4/6i) is the mainstay for the management of estrogen receptor–positive (ER+)/HER2-negative (HER2–) metastatic breast cancer as firdst-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 mutated tumors HR, 0.55; 95% CI, 0.39-0.77; all patients HR, 0.70; 95% CI, 0.55-0.88) with a manageable safety profile, leading to the first oral SERD approved. In a subgroup analysis in patients with ESR1-mutated tumors who had received prior ET plus CDK4/6i 12 months or more, 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). 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– metastatic breast cancer regardless of metastatic site and ESR1 status. The recommended phase 2 dose (RP2D) of the combination was determined to be elacestrant 345 mg once daily with abemaciclib 150 mg twice daily. 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.

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 or fewer chemotherapy regimens, and 0 to 2 prior CDK4/6i (excluding abemaciclib). The phase 2 primary objective is overall response rate per RECIST v1.1; secondary objectives include intracranial response rate, duration of response, clinical benefit rate, PFS, overall survival, pharmacokinetics, and quality of life.

Status

The phase 2 portion of ELECTRA is actively recruiting patients worldwide.