Comparison of Adjuvant Elacestrant with Standard Endocrine Therapy in High-Risk ER+/HER2- Early Breast Cancer
- Trial ID
- 2025-522484-15-00
- Protocol
- WSG-AM16
Trial statistics
Objectives
The primary objective of this study is to evaluate the efficacy of adjuvant elacestrant-containing therapy, with or without CDK4/6 inhibitor, compared to standard of care, with or without CDK4/6 inhibitor, in terms of improving invasive disease-free survival (iDFS) in patients with high-risk ER+/HER2- early breast cancer. Secondary objectives include the assessment of several clinical outcomes:
- Distant disease-free survival (dDFS), relapse-free survival (RFS), ductal carcinoma in situ disease-free survival (DFS-DCIS), invasive breast cancer-free survival (IBCFS), locoregional relapse-free survival (LRFS), and overall survival (OS).
- Health-related quality of life (HRQoL) utilizing standardized questionnaires.
- Toxicity profiles in both treatment arms.
Participants
The sponsor did not provide information regarding the total number of participants. The study population consists of adults, aged 18 years or older, diagnosed with ER+/HER2- early breast cancer. Eligible individuals include both male and female patients with histologically confirmed hormone-receptor-positive and HER2-negative invasive carcinoma of the breast. Participants must exhibit a high genomic risk and have no evidence of distant metastasis. Required clinical status includes an ECOG performance status of ≤ 1 or a Karnofsky Index of ≥ 80%. Selection is contingent upon the completion of endocrine induction treatment, adjuvant chemotherapy, or radiotherapy where applicable. Inclusion requires adequate laboratory parameters, a normal electrocardiogram, and the ability to swallow oral medication.
Plans and Procedures
This Phase III clinical trial evaluates the efficacy of elacestrant, with or without ribociclib, compared to standard-of-care endocrine treatment in patients with ER+/HER2- early breast cancer characterized by high genomic or clinical risk. The primary objective is to assess improvements in invasive disease-free survival (iDFS). The study follows a randomized design to compare the investigational regimen against the standard treatment protocol. Participants undergo a screening process to confirm eligibility based on histological diagnosis, genomic risk assessment, and various laboratory and clinical criteria. Following successful screening, the study includes follow-up assessments to monitor overall survival (OS), disease-free survival (DFS), and health-related quality of life (HRQoL). Clinical monitoring occurs at specific intervals, including 6-monthly assessments during the first three years of treatment and annually thereafter. The trial is estimated to conclude by September 2033. Early termination of participation may occur due to specific clinical conditions or requirements outlined in the study protocol.
Treatment
The experimental treatment involves elacestrant, which is administered as film-coated tablets. The available dosages are 86 mg and 345 mg, delivered via oral use.
The study also utilizes ribociclib, provided in film-coated tablets of 200 mg. The administered dose is 400 mg per oral use.
Efficacy
The primary efficacy endpoint is invasive disease-free survival (iDFS), which will be compared between patients randomized to adjuvant elacestrant-containing therapy, with or without ribociclib, and those receiving standard of care endocrine treatment, with or without ribociclib. Secondary endpoints include overall survival (OS), defined as the time from first diagnosis to death, distant disease-free survival (dDFS), recurrence-free survival (RFS), disease-free survival from ductal carcinoma in situ (DFS-DCIS), invasive breast cancer-free survival (IBCFS), and locoregional recurrence-free survival (LRFS), all as defined by STEEP 2.0. Additional secondary outcomes involve long-term survival endpoints and survival outcomes in premenopausal patients treated with ovarian function suppression (OFS) in combination with an aromatase inhibitor or tamoxifen, with or without ribociclib or elacestrant.
The assessment of health-related quality of life (HRQoL) will involve measuring changes from baseline. Measurements are scheduled after the completion of standard of care primary treatment, including neoadjuvant chemotherapy, surgery, and further local therapy. Specific timepoints for HRQoL assessments include the period before treatment initiation, every six months during treatment until year 3, and annually thereafter. Efficacy will also be evaluated through the comparison of toxicity profiles by assessing rates of adverse events of special interest (AESI), adverse drug reactions (ADR), serious adverse drug reactions (SADR), and serious adverse events (SAE).
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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/or 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).
- High genomic risk assessment within clinical routine (Oncotype DX® preferred; In those cases, where Oncotype Dx® is not possible in clinical routine, Oncotype Dx® should be assessed retrospectively after inclusion of the patient and as a study specific measure, provided sufficient tumour tissue from primary diagnosis is available.)
- 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): see protocol for details
- No contraindication for adjuvant SoC endocrine treatment
- No contraindication for elacestrant treatment
- No contraindication for ribociclib treatment, if medically indicated, and adequate washout time for CYP3A4 inducers/inhibitors or QT time- prolonging drugs
- Tumour block available for central pathology review (core biopsy of initial diagnosis and biopsy/surgery sample of definite surgery, if available)
- Performance Status ECOG ≤ 1 or Karnofsky Index ≥ 80%
- Laboratory requirements (female and male patients, not older than 14 days prior to date of informed consent): absolute neutrophil count ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L, haemoglobin ≥ 9.0 g/dL, INR ≤ 1.5, serum creatinine < 1.5 × ULN OR clearance ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN, total bilirubin < ULN, except for patients with Gilbert’s Syndrome who may only be included if the total bilirubin is ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN, aspartate transaminase (AST) < 2.5 × ULN, alanine transaminase (ALT) < 2.5 × ULN, Screening lipid panel fasting levels: total cholesterol ≤400 mg/dL AND/OR triglycerides <500 mg/dL.
- Clinical assessments: normal electrocardiogram within 6 weeks prior to randomization (QTcF interval at screening <450msec using Fridericia’s correction, mean resting heart rate 50-90 bpm)
- Ability to swallow tablets
- Contraception: see protocol for details
Exclusion Criteria
- 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
- For patients planned for ribociclib treatment: Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following: see protocol for details
- Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., uncontrolled ulcerative diseases, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome, or small-bowel resection).
- Uncontrolled infection requiring i.v. antibiotics, antivirals, or antifungals
- Active primary immunodeficiency, known human immunodeficiency virus (HIV) infection. Patients should be tested for HIV prior to randomization if required by local regulations or ethics committee (EC). Patients who test positive for HIV-antibody are excluded.
- Patient has known active hepatitis-B-virus (HBV) or hepatitis-C-virus (HCV) infection. Screening for HBV or HBC-infection and testing for hepatitis-B or -C is highly recommended according to current valid (local) clinical guidelines, but neither part of the interventional study procedures, nor required for enrolment.
- Patient has received live vaccines within 30 days prior to randomization.
- Patient was submitted to an institution by virtue of an order of a court or a governmental authority must be excluded from participation.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Not Yet Recruiting | 31 Mar 2026 | 180 |
 Germany | Recruiting | 31 Mar 2026 | 1050 |
 Spain | Not Yet Recruiting | 31 Mar 2026 | 290 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Kisqali 200 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL USE | 400 | 36 | PRD5341570 |
Kisqali 200 mg film-coated tablets | Test | FILM‑COATED TABLETS | ORAL USE | 400 | 36 | PRD5341565 |
Kisqali 200 mg film-coated tablets | Test | FILM‑COATED TABLETS | ORAL USE | 400 | 36 | PRD5341584 |
ORSERDU 345 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL USE | 345 | 260 | PRD10641184 |
ORSERDU 86 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL USE | 258 | 260 | PRD10641183 |
Kisqali 200 mg film-coated tablets | Test | FILM‑COATED TABLETS | ORAL USE | 400 | 36 | PRD5341583 |