The Menarini Group (“Menarini”) and Radius Health, Inc. (“Radius”) announced the presentation at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting of data from the EMERALD phase 3 clinical trial (NCT03778931). In a non-pre-specified subgroup analysis of patients with ER+/HER2- metastatic breast cancer (mBC) without prior chemotherapy in the metastatic setting, elacestrant significantly prolonged progression-free survival (PFS) compared to standard of care (SOC) endocrine therapy. EMERALD study met both of its pre-specified primary endpoints of progression free survival (PFS) in the overall population and in patients with ESR1 mutation (mESR1).

77.8% (n=371) out of the 477 patients enrolled in the trial had not received prior chemotherapy in the metastatic setting for ER+/HER2- mBC. Among these patients, elacestrant showed the following results compared to SOC: 31% reduction in the risk of progression or death in all patients (HR=0.681 [95% CI: 0.520 – 0.891]; P=0.00388) and prolonged median PFS (3.68 vs 1.97 months). 46% reduction in the risk of progression or death in patients with mESR1 (HR=0.535 [95% CI: 0.356 – 0.799]; P=0.00235) and prolonged median PFS (5.32 vs 1.91 months).

At 6 months, PFS rate with elacestrant was 38.18% vs. 23.47% with SOC in the overall population, and 43.79% vs. 23.83% in the ESR1 mutation population.

PFS rate at 12 months with elacestrant was 27.12% vs. 12.19% with SOC in the overall population, and 31.48% vs. 12.36% in the ESR1 mutation population.

In exploratory subgroup analyses, elacestrant significantly reduced the risk of progression or death and prolonged median PFS vs fulvestrant in all patients without prior chemotherapy (HR=0.636 [95% CI: 0.465-0.868]; median PFS 3.68 vs 1.97 months; P=0.0032), and in patients with mESR1 without prior chemotherapy (HR=0.487 (95% CI: 0.310-0.761; median PFS 5.32 vs 1.91 months; P=0.0015). Elacestrant had a manageable safety profile in patients without prior chemotherapy consistent with the overall population. Elacestrant is an investigational selective estrogen receptor degrader (SERD), out-licensed to Menarini Group, which is being evaluated for potential use as a once daily oral treatment in patients with ER+/HER2- advanced breast cancer.

In 2018, elacestrant received fast track designation from the FDA. Preclinical studies completed prior to EMERALD indicate that the compound has the potential for use as a single agent or in combination with other therapies for the treatment of breast cancer. The EMERALD Phase 3 trial is a randomized, open label, active-controlled study evaluating elacestrant as second- or third-line monotherapy in ER+/HER2- advanced/metastatic breast cancer patients.

The study enrolled 477 patients who have received prior treatment with one or two lines of endocrine therapy, including a CDK 4/6 inhibitor. Patients in the study were randomized to receive either elacestrant or the investigator's choice of an approved hormonal agent. The primary endpoint of the study was progression-free survival (PFS) in the overall patient population and in patients with estrogen receptor 1 gene (ESR1) mutations.

Secondary endpoints included evaluation of overall survival (OS), objective response rate (ORR), and duration of response (DOR).