Real-world evidence bolsters the efficacy of ORSERDU for the treatment of patients with ER+/HER2- ESR1-mut advanced or mBC.

Updated results of elacestrant in combination with abemaciclib show favorable efficacy regardless of the ESR1 mutation status,with a manageable and predictable safety profile in patients with ER+/HER2- mBC.

FLORENCE,ItalyandNEW YORK,Nov. 26,2024 -- 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 new and expanded data on ORSERDU® (elacestrant) at the upcoming 2024 San Antonio Breast Cancer Symposium (SABCS),December 10-13,2024. Of note,the company will bring real-world progression-free survival (rwPFS) results of ORSERDU in adult patients with ER+/HER2-,advanced or metastatic breast cancer (mBC). Additionally,the company will present updated efficacy results of elacestrant plus abemaciclib,along with a pooled safety analysis from phase 1b/2 of both the ELECTRA and ELEVATE trials.

ORSERDU Real-World Progression-Free Survival Data

ORSERDU is the first and only oral estrogen receptor antagonist (SERD) approved to target ESR1-mutated tumors,which occur in up to 50% of ER+,HER2- advanced or mBC tumors,as a result of prior exposure to endocrine therapy (ET) in the metastatic setting. Since its approval by the U.S. Food & Drug Administration (FDA) in January 2023,sufficient time has passed to be able to characterize the real-world use of ORSERDU in the current mBC treatment landscape.

Results to be reported at SABCS 2024 show the efficacy of ORSERDU in the real-world setting in patients with ER+/HER2- advanced or mBC. The overall population analysis demonstrated median rwPFS of 6.8 months. Median rwPFS for patients with 1-2 lines of prior ET in mBC was8 months. The rwPFS observed is consistent across the subgroups in the analysis. Updated results and additional information from other patient subgroups will be presented at the congress.

The full abstract (SESS-1876)can be viewed here (page 1748).

"These exciting data show clinically meaningful real-world progression-free survival with ORSERDU monotherapy," said Virginia Kaklamani,MD,DSc,breast medical oncologist and professor of medicine,UT Health San Antonio,MD Anderson Cancer Center. "As a practicing physician,these results underscore the need to test patients' tumors for the ESR1 mutation at each disease progression using liquid biopsy,so that we can appropriately tailor their treatment and optimize their care."

Elacestrant Plus Abemaciclib Combination Study

Both the ELEVATE and ELECTRA phase 1b/2 studies were designed with the objective to evaluate patient outcomes through combination treatment options,by overcoming a tumor's resistance to ET.

Results to be reported at SABCS 2024 include updated efficacy results from the ELECTRA study which demonstrate favorable progression-free survival (PFS) data. In all efficacy-evaluable patients,median progression-free survival (mPFS) was 8.6 months. In patients with an ESR1 mutation,mPFS was 8.7 months. In patients without an ESR1 mutation,mPFS was 7.2 months.

Additionally,a pooled safety analysis of patients from ELECTRA and ELEVATE show a manageable and predictable safety profile in patients with ER+/HER2- mBC that is treated with elacestrant plus abemaciclib,and who previously received one or more lines of prior therapy. Safety was evaluated in all patients who received this combination and was consistent with the known safety profiles of both compounds. The most common all-grade adverse events (AEs) (≥20%) were diarrhea,nausea,neutropenia,vomiting,fatigue,anemia and decreased appetite. No Grade 4 AEs were observed.

The full abstract (SESS-1910)can be viewed here (page 3330).

"These updated results on the combination of elacestrant plus abemaciclib continue to show encouraging progression-free survival data,and a favorable safety profile,without any new toxicity signals when using these agents in combination," said Hope S. Rugo,Professor of Medicine and Winterhof Family Endowed Professor in Breast Cancer,Director,Breast Oncology and Clinical Trials Education,University of California San Francisco. "Elacestrant continues to show potential to become an endocrine therapy backbone for combination regimens in metastatic breast cancer,and we are excited to explore this treatment combination further as these trials move forward."

"It is exciting to see these progression-free survival outcomes in a real-world setting,which shows ORSERDU brings a meaningful benefit for oncologists to offer their patients," saidElcin Barker Ergun,CEO of the Menarini Group. "We are committed to advancing our robust clinical research program on elacestrant and unlocking its full potential,both in monotherapy and combination treatment settings,with the goal of bringing ORSERDU to new patient populations which may benefit."

Menarini Stemline will also share results of other relevant data from the Phase 3 EMERALD trial,as well as several trials in progress.

Complete List of Menarini Stemline Abstracts:

Title: Elacestrant real-world progression-free survival (rwPFS) of adult patients with ER+/HER2-,advanced breast cancer: a retrospective analysis using insurance claims in the United States

Poster Number: P3-10-08

Date & Time: Thursday,December 12,12-2 PM CST

Location: TBC

Presenting Author: Elyse Swallow

Title:Elacestrant plus abemaciclib (abema) combination in patients (pts) with estrogen receptor-positive (ER+),HER2-negative (HER2-) advanced or metastatic breast cancer (mBC)

Poster Number: PS7-07

Date & Time: Thursday,7-8:30 AM CST

Location: TBC

Presenting Author: Hope Rugo

Title: Elacestrant combination in patients with estrogen receptor-positive (ER+),HER2-negative (HER2-) locally advanced or metastatic breast cancer (mBC): Update from ELEVATE,a phase 1b/2,open-label,umbrella study

Poster Number: PS7-06

Date & Time: Thursday,7-8:30 AM CST

Location:TBC

Presenting Author: Hope Rugo

Title: Elacestrant vs SOC in ER+,HER2- advanced or metastatic breast cancer (mBC) with ESR1-mutated tumors: ESR1 allelic frequencies and clinical activity from the phase 3 EMERALD trial

Poster Number: P1-01-25

Date & Time: Wednesday,December 11,12-2 PM CST

Location: TBC

Presenting Author: Aditya Bardia

Title: ELEGANT: Elacestrant versus standard endocrine therapy in women and men with node-positive,estrogen receptor-positive,HER2-negative,early breast cancer with high risk of recurrence in a global,multicenter,randomized,open-label phase 3 study

Poster Number: P2-08-21

Date & Time: Wednesday,5:30-7:30 PM CST

Location: TBC

Presenting Author: Aditya Bardia

Title: ADELA: A randomized,phase 3,double-blind,placebo-controlled trial of elacestrant plus everolimus versus elacestrant in ER+/HER2-advanced breast cancer (aBC) patients with ESR1-mutated tumors progressing on endocrine therapy (ET) plus CDK4/6i

Poster Number: P2-10-21

Date & Time: Wednesday,5:30-7:30 PM CST

Location: TBC

Presenting Author: Antonio Llombart-Cussac

Title: ELCIN: Elacestrant in women and men with CDK4/6 inhibitor (CDK4/6i)-naïve estrogen receptor-positive (ER+),HER2-negative (HER2-) metastatic breast cancer (mBC): An open-label multicenter phase 2 study

Poster Number: P2-08-20

Date & Time: Wednesday,5:30-7:30 PM CST

Location: TBC

Presenting Author: Virginia Kaklamani

About The Elacestrant Clinical Development Program

Elacestrant is also being investigated in several company-sponsored clinical trials in metastatic breast cancer,alone or in combination with other therapies. EMERALD (NCT03778931) is a randomized Phase 3 trial,open label,active-controlled study evaluating elacestrant as second- or third-line monotherapy in ER+,HER2- advanced/metastatic breast cancer patients. 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. ELEGANT (NCT06492616)is a phase 3 study evaluating elacestrant versus standard endocrine therapy in women and men with node-positive,early breast cancer with high risk of recurrence. 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 atwww.orserdu.com.

Important Safety Information

Warning and Precautions

Dyslipidemia:Hypercholesterolemiaandhypertriglyceridemiaoccurred in patients takingORSERDUat an incidence of 30% and 27%,respectively. The incidence of Grade 3 and 4hypercholesterolemiaandhypertriglyceridemiawere 0.9% and 2.2%,respectively. Monitor lipid profile prior to starting and periodically while takingORSERDU.

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 withORSERDU 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 reactionsoccurred 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. at1-877-332-7961 or FDA at1-800-FDA-1088orwww.fda.gov/medwatch.

About The Menarini Group

The Menarini Group is a leading international pharmaceutical and diagnostics company,with a turnover of $4.7 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 visitwww.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 the development and commercialization of novel oncology therapeutics. Stemline commercializes ORSERDU® (elacestrant) in the U.S. and Europe,an oral endocrine therapy indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive,ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. Stemline also commercializes ELZONRIS® (tagraxofusp-erzs),a novel targeted treatment directed to CD123 for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN),an aggressive hematologic cancer,in the United States and Europe,which is the only approved treatment for BPDCN in the U.S. and E.U. to date.Stemline also commercializes NEXPOVIO® (selinexor) in Europe,an XPO1 inhibitor for multiple myeloma. Stemline also has an extensive clinical pipeline of small molecules and biologics in various stages of development for a host of solid and hematologic cancers.