23 ELECTRA: An Open-Label, Multicenter, Phase 1b/2 Study of Elacestrant in Combination With Abemaciclib in Patients With Brain Metastasis From Estrogen Receptor–Positive (ER+), HER2-Negative (HER2) Breast Cancer (BC)
23 ELECTRA: An Open-Label, Multicenter, Phase 1b/2 Study of Elacestrant in Combination With Abemaciclib in Patients With Brain Metastasis From Estrogen Receptor–Positive (ER+), HER2-Negative (HER2) Breast Cancer (BC)
Background
Endocrine therapy (ET) plus CDK4/6 inhibitor is the mainstay for the management of estrogen receptor–positive (ER+)/HER2–negative metastatic breast cancer (mBC) as first-line therapy. However, tumors eventually develop resistance to ET, leading to disease progression. In the EMERALD phase 3 trial, single-agent elacestrant was associated with significantly prolonged progression-free survival (PFS) and a manageable safety profile vs standard-of-care (SOC) ET, leading to the first oral selective estrogen receptor degrader approved. Patients receiving elacestrant achieved a median PFS of 3.8 months vs 1.9 months with SOC (Bidard, 2022). Patients who received more than 12 months of prior CDK4/6i experienced an mPFS of 8.6 months with elacestrant vs 1.9 months with SOC. The rationale for the ELECTRA study is to combine elacestrant with abemaciclib in patients with brain metastases since both compounds have demonstrated the ability to cross the blood-brain barrier. Phase 1b evaluates the safety of the combination in patients regardless of brain metastases.
Methods
Eligible patients are those with ER+/HER2-negative advanced/mBC and measurable brain metastases. For phase 1b, the presence of brain metastases is not required for eligibility. For phase 2, patients must have 1 or more active and measurable brain metastases per RECIST v1.1. Patients must have received prior therapy in the metastatic setting, including 1 or more ET, 2 or less chemotherapy regimens, and 0 to 2 prior CDK4/6 inhibitors (excluding abemaciclib). The primary objective of phase 1b is to determine the recommended phase 2 dose combination of elacestrant plus abemaciclib regardless of brain metastases. Phase 2 will evaluate the objective response rate of the combination in patients with brain metastases. This analysis reports the 3 dose cohorts of the phase 1b portion.
Results
As of November 2023, 21 patients have been enrolled in the phase 1b portion of the trial (cohort 1, n = 8; cohort 2, n = 7; cohort 3, n = 6). No patients had brain metastases. No dose-limiting toxicities (DLTs) were observed during the observation period in the 3 cohorts, and no discontinuations have been observed for any patients beyond the observation period due to toxicity. The most common adverse effects were diarrhea, nausea, and neutropenia/neutrophil count decreased. There were no drug-drug interactions across all evaluated dose levels. Preliminary efficacy data showed antitumor activity of the combination in all cohorts.
Conclusion
In the phase 1b portion, no patients experienced DLTs, and no discontinuations have been observed. Preliminary efficacy results are encouraging for the combination, showing a tolerable and manageable safety profile. Phase 2 will further characterize the efficacy of the combination in patients with required brain metastases.
