On November 30, 2022 The Menarini Group ("Menarini"), a privately held Italian pharmaceutical and diagnostics company, and Stemline Therapeutics ("Stemline"), a wholly-owned subsidiary of the Menarini Group, will present additional data from the Phase 3 EMERALD study (NCT03778931) of elacestrant, an investigational oral SERD, during the upcoming San Antonio Breast Cancer Symposium (SABCS) being held from December 6-10 (Press release, Menarini, NOV 30, 2022, View Source;in-metast-301690442.html [SID1234624624]).

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EMERALD is a Phase 3 registrational trial that demonstrated statistically significant progression-free survival (PFS) with elacestrant vs SOC endocrine monotherapy (fulvestrant, letrozole, anastrozole, exemestane), meeting both primary endpoints in all patients and in those patients harbouring ESR1 mutations (ESR1-mut), following progression on prior CDK4/6 inhibitors (CDK4/6i) in ER+, HER2- advanced or metastatic breast cancer.

A post-hoc analysis of the PFS results in the EMERALD trial based on the duration of prior CDK4/6i usage shows clinically meaningful results which favor monotherapy elacestrant, both in the total patient population as well as in patients with ESR1-mut. Increased duration of prior CDK4/6i in metastatic patients was positively associated with longer PFS on elacestrant but not with SOC.

For those who were exposed to CDK4/6i ≥12 months prior to randomization on EMERALD, elacestrant achieved:

In the all-patient population, a mPFS of 3.8 months on elacestrant vs 1.9 months on SOC, a 39% reduction in the risk of progression or death (HR=0.61 95% CI: 0.45-0.83)
In the ESR1-mut population, a mPFS of 8.6 months on elacestrant vs 1.9 months on SOC, a 59% reduction in the risk of progression or death (HR=0.41 95% CI: 0.26-0.63)
For those who were exposed with CDK4/6i ≥18 months prior to randomization on EMERALD, elacestrant achieved:

In the all-patient population, a mPFS of 5.5 months on elacestrant vs 3.3 months with SOC, a 30% reduction in the risk of progression or death (HR=0.70 95% CI: 0.48-1.02)
In the ESR1-mut population, a mPFS of 8.6 months on elacestrant vs 2.1 months on SOC, a 53% reduction in the risk of progression or death (HR=0.47 CI: 0.20-0.79).
Updated safety data were consistent with previously reported results. Most of the adverse events (AEs), including nausea, were grade 1 and 2, and only 3.4% and 0.9% of the patients discontinued trial therapy because of an AE on elacestrant and SOC, respectively. A low percentage of patients received an antiemetic; 8.0% on elacestrant, 3.7% on fulvestrant, and 10.3% on AI, respectively. No hematological safety signal was observed and none of the patients in either of the two treatment arms had sinus bradycardia.

Virginia Kaklamani, MD, DSc, breast medical oncologist and professor of medicine, UT Health San Antonio, MD Anderson Cancer Center, commented, "These results show that when used as a single agent, elacestrant provided mPFS up to 8.6 months, based on the duration of previous CDK4/6 inhibitor therapy, with a manageable safety profile and the convenience of an oral tablet. This suggests elacestrant may have the potential to become a new standard of care as a monotherapy endocrine sequencing option in ER+, HER2- advanced breast cancer after progression on CDK4/6i, before moving to combination therapies."

"These results further highlight elacestrant’s potential to change the treatment paradigm of ER+, HER2- advanced or metastatic breast cancer. Elacestrant is under Priority Review with the U.S. Food and Drug Administration (FDA) with a target PDUFA date of February 17, 2023," commented Elcin Barker Ergun, Chief Executive Officer of the Menarini Group.

A complete list of key Menarini Group presentations at SABCS is below.

Lead Author Name

Abstract Number and Title

Presentation Details

V. Kaklamani

GS3-01. EMERALD Phase 3 trial of elacestrant versus standard of care endocrine therapy in patients with ER+, HER2- metastatic breast cancer: Updated results by duration of prior CDK4/6i in metastatic setting

December 8, 2022

8:30-8:45 AM CT

Oral Presentation

General Session 3

Hall 3

H. Rugo

OT2-01-03. ELEVATE: A Phase 1b/2, open-label, umbrella study evaluating elacestrant in various combinations in women and men with metastatic breast cancer (mBC)

December 7, 2022

5:00-6:30 PM CT

Ongoing Trials Poster Session 2

Hall 1

M. Piccart

PD18-05. MEN1611, a PI3K Inhibitor, combined with trastuzumab (T) ± fulvestrant (F) for HER2+/PIK3CA mutant (mut) advanced or metastatic (a/m) breast cancer (BC): updated safety and efficacy results from the ongoing Phase 1b study (B-PRECISE-01)

December 9, 2022

7:00-8:15 AM CT

Spotlight Poster Discussion 18

Stars at Night Ballroom – Hall 3&4

The Menarini Group obtained global licensing rights for elacestrant in July 2020 from Radius Health, Inc., who conducted and successfully completed the EMERALD study. The Menarini Group is now fully responsible for global registration, commercialization, and further development activities for elacestrant.

About Elacestrant (RAD1901) and the EMERALD Phase 3 Study

Elacestrant is an investigational selective estrogen receptor degrader (SERD). 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 478 patients who had 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 endpoints of the study were 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) and safety.