Marker - Adjusted Therapy Comparing Adjuvant Elacestrant With Standard Endocrine Treatment in Genomically and/or Clinically High-risk ER+/HER2- eBC

NCT07242352 | Recruiting Phase 3 DMC

• 2 other identifiers: WSG-AM16 (ADAPTela)2025-522484-15-00
• Study Type: interventional
• Target: 1,520
• Locations: 1 country
• Sites: 1

Brief Summary

In this clinical trial, the Sponsor plans to investigate whether patients with HR+/HER2- eBC identified during routine clinical assessments and treatments as having intermediate to high-risk (based on Oncotype DX® or similar tests and on response assessment to 2-6 weeks of preoperative ET) achieve a survival benefit from an initial 5-years use of elacestrant (with or without a CDK 4/6 inhibitor) followed by SoC ET for further 0-2.5 years in comparison to at least 5 up to 7.5 years SoC ET therapy (+/- CDK4/6 inhibitor). Based on several studies in the metastatic setting, it is reasonable to assume that the adjuvant use of elacestrant with or without CDK 4/6 inhibitors will prevent or delay the activation of mechanisms conferring resistance to ET (e.g., ESR1 mutations).

Conditions

Breast Cancer; HR+/HER2- Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 5-year invasive disease-free survival (iDFS)

  iDFS after 5 years, compared between patients randomized to adjuvant elacestrant (+/-CDK4/6i) or SOC ET (+/- CDK4/6i)

  iDFS 5 years

Secondary Outcomes (6)

• 5-year distant disease-free survival (dDFS)

  dDFS 5 years

• 5-year relapse-free survival (RFS)

  RFS 5 years

• 5-year DCIS disease-free survival (DFS-DCIS)

  DFS-DCIS 5 years

• 5-year invasive breast cancer-free survival (IBCFS)

  IBCFS 5 years

• 5-year locoregional relapse-free survival (LRFS)

  LRFS 5 years

Study Arms (2)

Elacestrant upfront (ELA)

EXPERIMENTAL

Patients will be treated with elacestrant (ELA) for 5 years. In case further treatment, e.g., CDK4/6 inhibitors, is indicated, ribociclib (RIBO) may be added for 3 years in parallel

Drug: Elacestrant

Standard-of-care endocrine treatment (SoC-ET)

ACTIVE COMPARATOR

Patients will be treated with SoC ET for 5-10 years. In case further treatment, e.g., CDK4/6 inhibitors, is indicated, this may be added according to SoC and per investigator´s discretion.

Drug: Standard-of-care endocrine treatment

Interventions

Elacestrant DRUG

Elacestrant, a tetrahydronaphthalene compound, is a potent, selective, and orally active oestrogen receptor-α (ERα) antagonist and degrader.

Also known as: ORSERDU

Elacestrant upfront (ELA)

Standard-of-care endocrine treatment DRUG

SoC ET comprises all endocrine treatments authorized for the condition under review. The choice is made upon investigator´s discretion.

Standard-of-care endocrine treatment (SoC-ET)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients, independent from gender
• Patient must be ≥18 years at diagnosis
• The patient must be capable of giving informed consent and be willing and able to comply with the requirements and restrictions in this protocol and accessible for treatment and follow-up
• Sign informed consent prior to any study-specific procedures.
• Histologically confirmed unilateral, primary invasive carcinoma of the breast Note: bilateral, multicentric, or multifocal carcinoma may only be included after consultation of Sponsor.
• Histologically confirmed diagnosis of primary hormone-receptor-positive (HR+) (i.e., oestrogen-receptor (ER) ≥ 10% and progesterone-receptor PR ≥ 10%) early breast cancer by local laboratory Note: ER positive according to ASCO / AGO Guidelines, ER 1-10% (low) is not defined as HR+.
• Patient has HER2-negative breast cancer defined as a negative in-situ hybridization test or an IHC status of 0, 1+, or 2+, if IHC is 2+, a negative in-situ hybridization (FISH, CISH, or SISH) test is required (based on the most recently analysed tissue sample and all tested by a local laboratory).
• No evidence of distant metastasis (confirmed by CT thorax / abdomen, X-ray chest, ultrasound liver, bone scan, or PET-CT, respectively, performed within clinical routine).
• \. Completed 2-6 weeks of endocrine induction treatment and Ki-67 response assessment Note: 2-4 weeks recommended, up to 6 weeks allowed. Endocrine induction is highly recommended, but if endocrine induction therapy could not be performed or ET response is not representative, clinical factors should be used.
• \. Completed (neo)adjuvant chemotherapy, if applicable
• Completed radiotherapy, if applicable
• Patient meets any of the following three conditions at end of primary treatment (including endocrine induction treatment, biopsy/surgery, and if necessary, chemotherapy and radiotherapy and up to 12 months standard-of-care endocrine treatment, excluding previous treatment \> 4 weeks with any SERD):
• Pathological Stage \* Genomical High-Risk (Oncotype Dx®)\*\* Age Clinical High-Risk Factors Stage I T1 N0
• RS\>25 Any age High risk (≤ 1 factor applies):
• ET non-response (post ET Ki-67 \>10%)\*\*\*

You may not qualify if:

• Known hypersensitivity to any of the compounds or incorporated substances of the IMPs
• Prior malignancy with a disease-free survival of \<5 years, except curatively treated basalioma of the skin or pTis of the cervix uteri
• Any history of invasive cancer within the last 10 years Note: adequately treated, basal or squamous-cell skin carcinoma, non-melanomatous skin cancer, curatively resected cervical cancer, and contralateral DCIS treated by mastectomy (contralateral in relation to current invasive breast cancer diagnosis) are excepted. Previous ipsilateral DCIS, irrespective of treatment, is excluded!
• Patient with distant metastases of breast cancer beyond regional lymph nodes.
• Concurrent treatment with cytotoxic agents for any non-oncological reason unless clarified with sponsor
• Concurrent treatment with other experimental drugs
• Participation in another interventional clinical trial with or without any investigational, not marketed drug within 30 days or 5 half-lives of the respective drug, whichever is longer, prior to study entry. In case of other interventional trial contact Sponsor.
• Previous treatment (\>4 weeks) with any SERD
• Concurrent pregnancy; patients of childbearing potential or potentially childbearing partners of male patients must implement a highly effective (less than 1% failure rate) non-hormonal contraceptive measures during the study treatment
• Breast feeding woman
• Use of oral, transdermal, injected, or implanted hormonal methods of contraception as well as hormonal replacement therapy (oestrogen or progesterone).
• Reasons indicating risk of poor compliance
• Patient not able to consent
• Patient has not recovered from clinical and laboratory acute toxicities related to prior anticancer therapies to NCI CTCAE version 5.0 Grade ≤ 1.
• Severe and relevant co-morbidity that would interact with the application of endocrine treatment of any kind or the participation in the study

Sponsors & Collaborators

• West German Study Group: lead
• Berlin-Chemie Menarini: collaborator

Study Sites (1)

Brustzentrum Niederrhein, Johanniter Bethesda Krankenhaus

Mönchengladbach, North Rhine-Westphalia, 41061, Germany

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

elacestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Peter Schmid, PHD Dr

  Fliethstraße 112-114 41061 Moenchengladbach Germany

  PRINCIPAL INVESTIGATOR

• NAdia Harbeck, Prof Dr

  Breast Centre, Dept. Obstetrics & Gynaecology and CCC Munich LMU University Hospital Munich Germany

  PRINCIPAL INVESTIGATOR

• Oleg Gluz, Prof Dr

  Breast Centre, Evang. Bethesda-Hospital Moenchengladbach Germany

  PRINCIPAL INVESTIGATOR

• Sherko Kuemmel, Prof Dr

  Breast Centre, Kliniken Essen Mitte Essen Germany

  PRINCIPAL INVESTIGATOR

• Monika Graeser, PD Dr

  Breast Centre, Marien-Hospital Witten Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anja Braschoß

CONTACT

004917682119153; regulatory@wsg-online.com

Marina Mangold, Dr.

CONTACT

00492161566 23-0; marina.mangold@wsg-online.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a multicentre, interventional, prospective, two-arm, randomised, open-label, controlled adjuvant, phase III-trial evaluating the efficacy and safety of elacestrant (combined with ribociclib, if applicable) versus standard-of-care (SoC) endocrine therapy (ET) in HR+/HER2- early breast cancer (eBC) patients.

Study Record Dates

• First Submitted: August 25, 2025
• First Posted: November 21, 2025
• Study Start: April 29, 2026
• Primary Completion (Estimated): September 30, 2033
• Study Completion (Estimated): September 30, 2033
• Last Updated: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)