EQS-News: Menarini Group Presents Elacestrant (ORSERDU®) Phase 2 Combination Data in Patients with ER+, HER2- Metastatic Breast Cancer (mBC) at the 2025 San Antonio Breast Cancer Symposium

• In addition, the expansive elacestrant clinical development program updates reinforce its potential as a backbone endocrine therapy in combination settings, as well as in both metastatic and early stage breast cancer.

FLORENCE, Italy and NEW YORK, Dec. 8, 2025 /PRNewswire/ -- The Menarini Group ("Menarini"), a leading international pharmaceutical and diagnostics company, and Stemline Therapeutics, Inc. ("Stemline"), a wholly-owned subsidiary of the Menarini Group, focused on bringing transformational oncology treatments to cancer patients, will present updated meaningful median progression-free survival (mPFS) efficacy results from two combination regimens of the Phase 2 ELEVATE study in patients with estrogen receptor-positive (ER+), HER2-negative (HER2-) locally advanced or metastatic breast cancer (mBC). The ELEVATE study was designed to evaluate the safety and efficacy of oral-oral combination treatment options to overcome different resistance mechanisms observed in ER+/HER2- mBC with the goal of improving patient outcomes. These data will be presented at the 2025 San Antonio Breast Cancer Symposium (SABCS), December 9-12.

"The encouraging progression-free survival data increase our confidence in the role elacestrant could play as an endocrine therapy backbone in the combination setting," said Virginia Kaklamani, MD, DSc, Professor of Medicine in the Division of Hematology/Oncology at UT Health San Antonio, and Leader of the Breast Cancer Program at UT Health San Antonio MD Anderson Cancer Center. "The safety profile of elacestrant in combination with everolimus or abemaciclib is consistent with the known safety profiles of each drug. No new safety signals have been observed."

The ELEVATE data to be presented at SABCS demonstrate that elacestrant in combination with everolimus or with abemaciclib shows a consistent PFS benefit, irrespective of ESR1 mutation status in patients with ER+/HER2- mBC, who experience disease progression on endocrine therapy (ET), with or without prior exposure to CDK4/6 inhibitors. These updated results also show that the safety of the combinations are consistent with the known safety profiles of each targeted therapy plus standard of care endocrine therapy.

Phase 2 mPFS in months (95% CI) in all patients and subgroups

"The extensive evidence for elacestrant spans the monotherapy setting in our pivotal EMERALD study, now backed by two recent real-world data publications^{[1], [2]}, and in its growing potential in combination regimens, as highlighted by the data presented at SABCS," said Elcin Barker Ergun, CEO of the Menarini Group. "We remain deeply committed to fully exploring elacestrant's potential benefit across multiple ongoing trials in both early stage and metastatic breast cancer."

Additionally, other elacestrant updates will be presented at SABCS, investigating its potential across the spectrum of breast cancer:

Presentation Title: Elacestrant in combination with everolimus or abemaciclib in patients with ER+/HER2-locally advanced or metastatic breast cancer (mBC): phase 2 results from ELEVATE, an open-label, umbrella study
Abstract Number: 1255
Presentation Date & Time: Thursday, December 11, 2025, 1:00 – 2:00 PM
Location: Hemisfair1-2
Presenting Author: Hope S. Rugo

Presentation Title: Elacestrant alone or in combination with triptorelin in premenopausal women with ER+/HER2-early breast cancer: primary analysis from the phase 2 SOLTI-2104-PremiÈRe trial
Abstract Number: 1123
Presentation Date & Time: Friday, December 12, 2025, 7:30 – 7:33 AM
Location: 301 ABC
Presenting Author: Mertixell Bellet

Presentation Title: ELEGANT: Elacestrant Versus Standard Endocrine Therapy (ET) in Women and Men With Node-positive, Estrogen Receptor-positive (ER+), HER2-negative (HER2-), Early Breast Cancer (eBC) With High Risk of Recurrence in a Global, Multicenter, Randomized, Open-label Phase 3 Study.
Abstract Number: 1276
Presentation Date & Time: Thursday, December 11, 2025, 12:30 – 2:00 PM
Location: Henry B. Convention Center
Presenting Author: Aditya Bardia

Presentation Title: The ADELA study: A Double-blind, Placebo-controlled, Randomized Phase 3 Trial of Elacestrant (ELA)+ Everolimus (EVE) Versus ELA + Placebo (PBO) in ER+/HER2-Advanced Breast Cancer (aBC) Patients with ESR1-mutated Tumors Progressing on Endocrine Therapy (ET) + CDK4/6i
Abstract Number: 1141
Presentation Date & Time: Wednesday, December 10, 2025, 12:30 – 2:00 PM
Location: Henry B. Convention Center
Presenting Author: Antonio Llombart-Cussac

Presentation Title: ERADICATE: A phase Ib/II study of elacestrant plus trastuzumab deruxtecan in patients with CDK4/6 inhibitor and endocrine-resistant HR+/HER2-low or HER2-ultralow metastatic breast cancer
Abstract Number: 2119
Presentation Date & Time: Friday, December 12, 2025, 12:30 – 2:00 PM
Location: Henry B. Convention Center
Presenting Author: Sara L. Sammons

Presentation Title: Hormonal receptor (HR)-positive HER2 negative breast cancer patients treated with preoperative Elacestrant and PULSAR adaptive radiotherapy: a phase II study (HELP Trial)
Abstract Number: 1071
Presentation Date & Time: Friday, December 12, 2025, 12:30 – 2:00 PM
Location: Henry B. Convention Center
Presenting Author: Luca Visani

About The Elacestrant Clinical Development Program

Elacestrant is also being investigated in several company-sponsored clinical trials in metastatic breast cancer disease, alone or in combination with other therapies. ELEVATE (NCT05563220) is a phase 1b/2 clinical trial evaluating the safety and efficacy of elacestrant combined with alpelisib, everolimus, capivasertib, palbociclib, ribociclib or abemaciclib. ELECTRA (NCT05386108) is an open-label phase 1b/2, multicenter study evaluating elacestrant in combination with abemaciclib in patients with ER+, HER2- breast cancer. The phase 2 portion evaluates this treatment regimen in patients with brain metastases. ELCIN (NCT05596409) is a phase 2 trial evaluating the efficacy of elacestrant in patients with ER+, HER2- advanced/metastatic breast cancer who received one or two prior hormonal therapies and no prior CDK4/6 inhibitors in the metastatic setting. ADELA (NCT06382948) is a phase 3 randomized, double-blinded trial evaluating elacestrant in combination with everolimus in patients with ER+, HER2- mBC with ESR1-mut tumors. Elacestrant is also being evaluated in additional investigator-led trials, in trials conducted in collaboration with other companies, in metastatic breast cancer as well as in early disease.

About ORSERDU (elacestrant)
U.S. Indication: ORSERDU (elacestrant), 345 mg tablets, is indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.

Full prescribing information for the U.S. can be found at www.orserdu.com.

Important Safety Information
Warning and Precautions

Dyslipidemia: Hypercholesterolemia and hypertriglyceridemia occurred in patients taking ORSERDU at an incidence of 30% and 27%, respectively. The incidence of Grade 3 and 4 hypercholesterolemia and hypertriglyceridemia were 0.9% and 2.2%, respectively.  Monitor lipid profile prior to starting and periodically while taking ORSERDU.

Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, ORSERDU can cause fetal harm when administered to a pregnant woman.  Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the final dose.

Adverse Reactions

Serious adverse reactions occurred in 12% of patients who received ORSERDU. Serious adverse reactions in >1% of patients who received ORSERDU were musculoskeletal pain (1.7%) and nausea (1.3%). Fatal adverse reactions occurred in 1.7% of patients who received ORSERDU, including cardiac arrest, septic shock, diverticulitis, and unknown cause (one patient each).
The most common adverse reactions (>10%), including laboratory abnormalities, of ORSERDU were musculoskeletal pain (41%), nausea (35%), increased cholesterol (30%), increased AST (29%), increased triglycerides (27%), fatigue (26%), decreased hemoglobin (26%), vomiting (19%), increased ALT (17%), decreased sodium (16%), increased creatinine (16%), decreased appetite(15%), diarrhea(13%), headache (12%), constipation (12%), abdominal pain (11%), hot flush (11%), and dyspepsia (10%).

Drug interactions

Concomitant use with CYP3A4 Inducers and/or inhibitors: Avoid concomitant use of strong or moderate CYP3A4 inhibitors with ORSERDU. Avoid concomitant use of strong or moderate CYP3A4 inducers with ORSERDU.

Use in specific populations

Lactation: Advise lactating women to not breastfeed during treatment with ORSERDU and for 1 week after the last dose.
Hepatic Impairment: Avoid use of ORSERDU in patients with severe hepatic impairment (Child-Pugh C). Reduce the dose of ORSERDU in patients with moderate hepatic impairment (Child-Pugh B).
The safety and effectiveness of ORSERDU in pediatric patients have not been established.

To report SUSPECTED ADVERSE REACTIONS, contact Stemline Therapeutics, Inc. at 1-877-332-7961 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

About The Menarini Group

The Menarini Group is a leading international pharmaceutical and diagnostics company, with a turnover of $5 billion and over 17,000 employees. Menarini is focused on therapeutic areas with high unmet needs with products for cardiology, oncology, pneumology, gastroenterology, infectious diseases, diabetology, inflammation, and analgesia. With 18 production sites and 9 Research and Development centers, Menarini's products are available in 140 countries worldwide. For further information, please visit www.menarini.com.

About Stemline Therapeutics Inc.
Stemline Therapeutics, Inc. ("Stemline"), a wholly-owned subsidiary of the Menarini Group, is a commercial-stage biopharmaceutical company focused on bringing transformational oncology treatments to patients. Stemline commercializes elacestrant, an oral endocrine therapy indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy, in the U.S., Europe, and other global regions. Stemline also commercializes tagraxofusp-erzs, a novel targeted therapy directed to CD123, for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive hematologic cancer, in the United States, Europe, and other global regions. In addition, Stemline commercializes selinexor, an XPO1 inhibitor for multiple myeloma, in Europe. The company is also conducting multiple label-expansion studies with elacestrant and tagraxofusp in breast and hematologic cancer indications, respectively, and has an extensive clinical pipeline of additional drug candidates in various stages of development for a host of solid and hematologic cancers.

[1] Lloyd et al. Clinical and genomic factors associated with elacestrant outcomes in ESR1-mutant metastatic breast cancer. Clin Cancer Res (2025). https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-25-3033/768341/Clinical-and-Genomic-Factors-Associated-with

[2] Rugo et al. Real-World Outcomes of Elacestrant in ER+, HER2-, ESR1-mutant Metastatic Breast Cancer. Clin Cancer Res, 2025. CCR-25-3040R1. https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-25-3040/768340/Real-World-Outcomes-of-Elacestrant-in-ER-HER2-ESR1

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