ABCSG 63 / ERIKA: Elacestrant and RIbociclib in Ki67-tested endocrine responsive breAst cancer: An open-label, two-arm, randomized, phase II study of elacestrant plus ribociclib vs. AI (plus GnRH agonist in pre-/perimenopausal women and men) plus ribociclib as neoadjuvant therapy for endocrine-responsive HER2-negative early breast cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Verein Zur Praevention Und Therapie Boesartiger Erkrankungen Austrian Breast And Colorectal Cancer Study Group

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

21 Aug 2025 → ongoing

Decision date (initial)

2025-04-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

A. Menarini Research & Business Service GmbH · Novartis Pharma GmbH

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To evaluate the superiority of elacestrant plus ribociclib vs. AI (and GnRH agonist in pre-/perimenopausal women and men) plus ribociclib in endocrine-responsive early breast cancer, when measured by modified PEPI score at the time of surgery

Secondary objectives 5

1. To evaluate the fraction of endocrine-responsive tumors in all randomized patients, when measured by Ki-67 (via C1D22 visit biopsy)
2. To evaluate the concordance of Ki-67 when determined by local pathology vs. central pathology (via C1D22 visit biopsy)
3. To evaluate the superiority of elacestrant plus ribociclib vs. AI (and GnRH agonist in pre-/perimenopausal women and men) plus ribociclib in endocrine-responsive early breast cancer, when measured by the RCB at the time of surgery
4. To evaluate the superiority of elacestrant plus ribociclib vs. AI (and GnRH agonist in pre-/perimenopausal women and men) plus ribociclib in endocrine-responsive early breast cancer, when measured by the pCR at the time of surgery
5. To evaluate changes in the radiological tumor size in response to the treatment of elacestrant plus ribociclib vs. AI (and GnRH agonist in pre-/perimenopausal women and men) plus ribociclib in endocrine-responsive early breast cancer from screening to 3 months (C4D1 visit) of treatment and to pre-surgery (surgery visit)

Conditions and MedDRA coding

endocrine-responsive HER2-negative early breast cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. (1) Signed informed consent obtained prior to any study specific assessments and procedures which are not performed as part of standard of care
2. (2) Women or men, age ≥ 18 years at the time of initially signing the study specific informed consent form(s) (ICF). Female patients may be either postmenopausal, premenopausal or perimenopausal. Refer to section 11.2, for definitions on the menopausal status.
3. (3) Histologically confirmed invasive, (unilateral or bilateral) adenocarcinoma of the breast with the following characteristics: - cT1c-4a-c, cN0-3, M0 per AJCC (American Joint Committee on Cancer) Breast Cancer Staging version 8 (refer to section 23.3); - In case of a multifocal tumor (defined as the presence of two or more foci of cancer within the same breast quadrant) or multicentric tumor (defined as the presence of two or more foci of cancer within different quadrants), the overall largest lesion must be > 1 cm and designated as the “target” lesion for all subsequent tumor evaluations; - Histologically confirmed HER2-negative tumors; HER2 measurement to be assessed locally according to the ASCO/CAP guideline; - ER-positive tumors (i.e. > 10 % positive stained tumor cells); - PR-positive or negative tumors
4. (4) ECOG performance status 0-1
5. (5) In women of childbearing potential, urine or serum pregnancy test must be negative within 28 days prior to randomization. In postmenopausal women or hysterectomized patients, pregnancy tests do not need to be performed. - Women of childbearing potential and men must use adequate contraception that results in a failure rate <1 % per year during the study treatment. In case of women of childbearing potential, until 180 days after the last dose of study treatment and in case of men with female partners of childbearing potential, until 120 days after the last dose of study treatment; - - Men or women must abstain from donating sperm or ova during the study treatment. In case of women, until 180 days after the last dose of study treatment and in case of men, until 120 days after the last dose of study treatment
6. (6) Absolute neutrophile count (ANC) ≥ 1.5 x 109/L (1500/µL) without granulocyte colony-stimulating factor (G-CSF) support
7. (7) Platelet count ≥ 100 x 109/L (100,000/µL) without transfusion
8. (8) Hemoglobin ≥ 90 g/L (9 g/dL). Patients may be transfused only once to meet this criterion
9. (9) For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN. For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
10. (10) Serum potassium ≥3mmol/L, serum sodium ≥130mmol/L, serum calcium ≤2.9mmol/L, serum albumin ≥3.0 g/dL (≥30 g/L), serum phosphate ≥2.5mg/dL and serum magnesium ≥0.5mmol/L (intake of (multi)vitamin supplements allowed)
11. (11) Aspartate amino transferase (AST), alanine amino transferase (ALT), and alkaline phosphatase (ALP) < 3 x ULN
12. (12) Total serum bilirubin ≤1.5 x ULN with the following exception: Patients with known Gilbert’s syndrome: total serum bilirubin level ≤ 3.0 x ULN or direct bilirubin ≤1.5 x ULN
13. (13) Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min (calculated using the Cockcroft-Gault formula); - - Creatinine clearance (male) = ([140-age in years] × weight in kg)/ ([serum creatinine in mg/dL] × 72); - - Creatinine clearance (female) = (0.85 × [140-age in years] × weight in kg)/ ([serum creatinine in mg/dL] × 72)
14. (14) Patients must have a 12-lead ECG with all of the following parameters at screening: - QTcF interval (using Fridericia’s correction) < 450 ms; - Resting heart rate ≥ 50 bpm
15. (15) Willingness and ability to provide FFPE tumor tissues and liquid biopsies for mandatory translational research program

Exclusion criteria 15

1. (1) Metastatic or locally advanced disease (without loco-regional treatment options with curative intention) as per local standard
2. (2) Patients receiving any prior systemic cancer therapy for invasive breast cancer
3. (3) Patients with a history of any malignancy are ineligible except for the following circumstances: - Patients with a malignancy history other than invasive breast cancer if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy; - Patients with a history of completely resected non-metastatic, non-melanoma skin cancer; - Patients with a history of successfully treated in situ carcinoma; - Patients with a contralateral breast carcinoma in situ; - - Patients with an ipsilateral breast carcinoma in situ (only in case in situ carcinoma is a separate lesion and not a component of the invasive breast cancer per histology report of biopsied invasive target lesion)
4. (4) Pregnant or lactating women
5. (5) Concurrent participation in another clinical trial with the same primary endpoint and/or concurrent participation in another clinical trial with a therapeutic investigational product
6. (6) Known hypersensitivity to the study drugs or its excipients (incl. peanut and soy)
7. (7) Patients unable to swallow normally and to take tablet and capsules (predictable poor compliance to oral treatment per investigator’s assessment)
8. (8) Medical history or ongoing gastrointestinal disorders potentially affecting the absorption of elacestrant and/or ribociclib (e.g., uncontrolled ulcerative diseases, uncontrolled/refractory/chronic nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel/significant gastric resection)
9. (9) Patient has had major surgery within 28 days prior to randomization or has not recovered from major side effects (as per investigator’s assessment)
10. (10) Serious medical or psychiatric disorders that would, in the investigator’s judgement, interfere with the patient’s safety or informed consent (e.g., known chronic pancreatitis, known chronic active hepatitis, known active untreated or uncontrolled fungal, bacterial or viral infections; - Patients with known HBV and/or HCV infection (testing only required, if clinically indicated) must have undetectable viral load during screeningns, etc.); - Patients known to be HIV+ (testing only required, if clinically indicated) are allowed if they have undetectable viral load at screening
11. (11) Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including but not limited to any of the following: - History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening; - - History of documented congestive heart failure (New York Heart Association functional classification III-IV); - Documented cardiomyopathy; - - Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third-degree AV block); - - Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: - i. Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia; - ii. Inability to determine the QTcF interval (Fridericia’s correction) during screening; - Systolic blood pressure (SBP) >160 mmHg or <90 mmHg at screening
12. (12) Documented pneumonitis/ILD prior to randomization
13. (13) Patient is currently receiving or has received any of the following medications that cannot be discontinued within 14 days or 5 half-lives, whichever is shorter, prior to first dose of the study: - Herbal preparations/medications known as strong inducers or inhibitors of CYP3A4 or those with a known risk of QT prolongation. These include, but are not limited to, St. John’s wort, kava, ephedra (ma huang), gingko biloba, DHEA, yohimbe, saw palmetto, and ginseng; - Medications, and/or foods including fruits (e.g., grapefruit, pumeloes, star fruit, Seville oranges) and their juices that are known strong and moderate inducers or inhibitors of CYP3A4; - Medications with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued or replaced by safe alternative medication 14 days prior to randomization; - Medications that have a narrow therapeutic index and are predominantly metabolized through CYP3A4/5; - Systemic corticosteroids
14. (14) Patients receiving live, attenuated vaccine within 7 days prior to randomization AND not fit for study participation as per investigator’s assessment
15. (15) Drugs that have an influence on the status of sex hormones, e.g., additional hormonal treatments (either oral or transdermal) including estrogen, progesterone hormone replacement therapy including megestrol acetate, oral or other types of hormonal contraceptives (including implants and depot injections), hormonal stimulation of ovaries (i.e., oocytes cryopreservation, IVF or ICSI), selective estrogen modulators (e.g., basedoxifene, ospemifene, raloxifene, tamoxifen)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of modified PEPI score of 0 at the time of surgery

Secondary endpoints 5

1. Proportion of endocrine-responsive tumors (i.e., Ki-67 10 %) determined by local pathology via C1D22 biopsy
2. Locally and centrally measured Ki-67 (via C1D22 visit biopsy)
3. Proportion of RCB 0/I at the time of surgery determined by local pathology
4. Proportion of pCR at the time of surgery
5. Change of radiological tumor size from screening to 3 months of treatment and to pre-surgery

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Verein Zur Praevention Und Therapie Boesartiger Erkrankungen Austrian Breast And Colorectal Cancer Study Group

Sponsor organisation

Verein Zur Praevention Und Therapie Boesartiger Erkrankungen Austrian Breast And Colorectal Cancer Study Group

Address

Nussdorfer Platz 8/8/12, Doebling Doebling

City

Vienna

Postcode

1190

Country

Austria

Scientific contact point

Organisation

Verein Zur Praevention Und Therapie Boesartiger Erkrankungen Austrian Breast And Colorectal Cancer Study Group

Contact name

Trial Office

Public contact point

Organisation

Verein Zur Praevention Und Therapie Boesartiger Erkrankungen Austrian Breast And Colorectal Cancer Study Group

Contact name

Trial Office

Third parties 5

Locations

2 EU/EEA countries · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 36 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications