European Organisation for Research and Treatment of Cancer & the Menarini Group Launch New Clinical Trial in Early-Stage Breast Cancer

• Trial expected to screen more than 1900 early-stage breast cancer patients at 120+ sites in 12 countries across Europe, commencing in Q4 2023
• Study will evaluate whether elacestrant can delay occurrence of metastasis or death compared to standard adjuvant endocrine therapy in early-stage ER+/HER2-breast cancer patients with late ctDNA-relapse

BRUSSELS and FLORENCE, Italy, Oct. 19, 2023 /PRNewswire/ -- The European Organisation for Research and Treatment of Cancer (EORTC) and the Menarini Group (Menarini), a leading international pharmaceutical and diagnostics company, today announced they have launched a new study for breast cancer patients: EORTC 2129-BCG TREAT ctDNA, a clinical trial supported by the EORTC Breast Cancer Group.  Menarini and its subsidiary, Stemline, will provide elacestrant. A molecular residual disease (MRD) test for the detection of circulating tumour DNA (ctDNA) will also be used. The study was submitted under the new Clinical Trial Regulation, and it is expected to start the activation process in the fourth quarter of 2023.

ORSERDU® (elacestrant) was approved by the European Commission in September 2023 as a monotherapy for the treatment of postmenopausal women, and men, with estrogen receptor (ER)–positive, HER2-negative, locally advanced or metastatic breast cancer (mBC) with an activating ESR1 mutation who have disease progression following at least one line of endocrine therapy including a CDK4/6 inhibitor.

"We are excited to offer to our high-risk, ctDNA positive, ER+/HER2- early-stage breast cancer patients the possibility to participate in the Treat ctDNA trial. ctDNA positive patients will be identified using a personalised assay. We aim to study the value of the new selective estrogen receptor degrader (SERD), elacestrant, in reducing the rate of late distant relapses for these patients," said Prof. Michail Ignatiadis, chair of the EORTC Breast Cancer Group and Director of the Breast Medical Oncology Clinic and Program at the Jules Bordet Institut. 

This intergroup trial, managed by the EORTC Breast Cancer Group, will be jointly conducted with several national and international cancer clinical research groups, including the German SUCCESS group under the umbrella of BIG (Breast International Group).  Twelve countries have been selected to participate in the trial (Italy, France, Belgium, Spain, Ireland, Cyprus, Germany, Greece, the Netherlands, Portugal, Sweden and Switzerland) with more than 120 sites expected to screen approximately 1960 patients.  The randomised, open label, superiority phase III trial will evaluate whether elacestrant can delay the occurrence of metastasis or death compared to standard adjuvant endocrine therapy in patients with early-stage ER+/HER2- breast cancer and molecular relapse. 

"The Menarini Group is glad to partner with EORTC on this important study, to expand our understanding of how elacestrant may potentially benefit ER+/HER2- patients with early-stage breast cancer," said Elcin Barker Ergun, CEO of the Menarini Group.  "Evaluating new treatments with a manageable safety profile, such as elacestrant, is important as we seek new options for this population."

After verification that patients meet the eligibility criteria, they will enter the ctDNA screening phase of the study, in which plasma samples will be collected and tested the to detect the presence of ctDNA. The test will be performed every six months from study entry until the end of accrual. Patients with a positive ctDNA test, who do not have metastasis and who fulfill the eligibility criteria, will be randomised to either the standard endocrine treatment arm (the same treatment they were receiving before detection of ctDNA) or to the elacestrant arm.  Patients will be randomised to one of the two treatment arms within four weeks of receiving their test results, with the goal of randomising 110 patients in each arm.  Patients in both the control and experimental
arms will benefit from timely detection of macroscopic disease relapse.

About elacestrant (ORSERDU®)

European Union Indication: ORSERDU (elacestrant) monotherapy is indicated for the treatment of postmenopausal women, and men, with estrogen receptor (ER)-positive, HER2-negative, locally advanced or metastatic breast cancer with an activating ESR1 mutation who have disease progression following at least one line of endocrine therapy including a CDK4/6 inhibitor.

Important Safety Information from the ORSERDU SmPC

Hepatic Impairment: Administration of ORSERDU should be undertaken with caution at a dose of 258 mg once daily in patients with moderate hepatic impairment (Child-Pugh B). In the absence of clinical data, ORSERDU is not recommended in patients with severe hepatic impairment (Child-Pugh C).

Concomitant use with CYP3A4 Inducers and/or inhibitors:  Concomitant use of strong or moderate CYP3A4 inhibitors with ORSERDU should be avoided. Concomitant use of strong or moderate CYP3A4 inducers with ORSERDU should be avoided.

Thromboembolic events: Thromboembolic events are commonly observed in patients with advanced breast cancer and have been observed in clinical studies with ORSERDU. This should be taken into consideration when prescribing ORSERDU to patients at risk.

Adverse Reactions:

Serious adverse reactions reported in ≥ 1% of patients included nausea, dyspnoea, and thromboembolism (venous).

The most common (≥ 10%) adverse reactions with ORSERDU were nausea, triglycerides increased, cholesterol increased, vomiting, fatigue, dyspepsia, diarrhoea, calcium decreased, back pain, creatinine increased, arthralgia, sodium decreased, constipation, headache, hot flush, abdominal pain, anaemia, potassium decreased, and alanine aminotransferase increased.

The most common Grade ≥3 (≥2%) adverse reactions of elacestrant were nausea (2.7%), AST increased (2.7%), ALT increased (2.3%), anaemia (2%), back pain (2%), and bone pain (2%).

Nausea: Nausea was reported in 35% of patients. Grade 3-4 nausea events were reported in 2.5% of patients. Nausea occurred more frequently in the first cycle and from Cycle 2 onward, the incidence of nausea was generally lower in subsequent cycles (i.e., over time). 

Elderly: Gastrointestinal disorders were reported more frequently in patients aged ≥ 75 years.

Fertility, pregnancy, and lactation:

ORSERDU should not be used during pregnancy or in women of childbearing potential not using contraception. Based on the mechanism of action of elacestrant and findings from reproductive toxicity studies in animals, ORSERDU can cause foetal harm when administered to pregnant women. Females of reproductive potential should be advised to use effective contraception during treatment with ORSERDU and for one week after the last dose.

It is recommended that lactating women should not breast-feed during treatment with ORSERDU and one week after the last dose of ORSERDU.

Based on findings from animal studies and its mechanism of action, ORSERDU may impair fertility in females and males of reproductive potential.

Effects on ability to drive and use machines: Fatigue, asthenia, and insomnia have been reported in some patients taking ORSERDU. Caution should be observed by patients who experience those adverse reactions when driving or operating machinery.

The safety and efficacy of ORSERDU in children from birth to 18 years of age has not been established.

To report SUSPECTED ADVERSE REACTIONS: EUPV@menarinistemline.com
To Report a Product Complaint: EUcustomerservice@menarinistemline.com
To Request Medical Information: EUmedinfo@menarinistemline.com 

Elacestrant is also being investigated in several clinical trials in metastatic breast cancer disease, alone or in combination with other therapies: ELEVATE (NCT05563220); ELECTRA (NCT05386108); and ELCIN (NCT05596409). Elacestrant is also planned to be evaluated in early breast cancer disease.

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

About EORTC Breast Cancer Group

The EORTC Breast Cancer Group (BCG) is a group of the most important academic hospitals in Europe aiming to develop new standards of care for breast cancer patients through innovation. Our research focus is the evaluation of innovative treatments and multidisciplinary approaches to increase survival and improve quality of life of all breast cancer patients.

About The Menarini Group

The Menarini Group is a leading international pharmaceutical and diagnostics company, with a turnover of over $4.4 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

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 United States and in the E.U., 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.  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 US and EU to date. Stemline also commercializes NEXPOVIO® 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.

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