Evaluating the Addition of Elacestrant (Oral SERD) to Olaparib (PARP-inhibitor) in Patients With Advanced/Metastatic HR+/HER2- Breast Cancer (ELEMENT)

November 24, 2025 updated by: GBG Forschungs GmbH

Phase II Study Evaluating the Addition of Elacestrant, an Oral Selective Estrogen Receptor Degrader (SERD), to Standard-of-care Olaparib in Patients With Hormone Receptor (HR)-Positive, HER2-negative Locally Advanced or Metastatic Breast Cancer With gBRCA1/2 Mutations

Trial design:

Phase II, prospective, multi-center, randomized, open label, parallel group study in patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with gBRCA1/2 mutation, with 2:1 randomization into Arm A (olaparib + elacestrant) or arm B (olaparib). Treatment in either arm will be given until disease progression, unacceptable toxicity, withdrawal of patient´s consent to study participation, or end of study.

Trial population:

Patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with gBRCA1/2 mutation, with an indication for standard-of-care PARP inhibitor therapy and planned treatment with olaparib, an ECOG performance status of 0-2 and life expectancy of > 6 months, with normal bone marrow and kidney functions and no active or newly diagnosed central nervous system (CNS) metastases or symptomatic metastatic visceral disease at risk of life-threatening complications.

Interventions:

Patients randomized to Arm A will receive 600 mg olaparib daily and 400 mg elacestrant daily, while patients randomized to Arm B will receive 600 mg olaparib daily. Blood tests (hematology, biochemistry) will be performed at the beginning of every cycle, and imaging for tumor assessment (chest and abdominopelvic imaging) as well as QoL assessments will be performed every three months and in case of suspicion of progression/end of study.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Patients with HR-positive, HER2-negative advanced or metastatic breast cancer and gBRCA1/2 mutations have a low progression-free survival (PFS) and represent a patient population with a high unmet need, hence further treatment options should be explored to improve patient outcomes.

Elacestrant is a novel, nonsteroidal, orally bioavailable estrogen receptor antagonist (SERD) that has shown efficacy in heavily pretreated patients with HR-positive, HER2-negative breast cancer, and in those with ESR1 mutations known to confer endocrine resistance, and has thus gained approval in 2023 by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of ET.

Olaparib is approved by the EMA for deleterious or suspected deleterious gBRCA-mutated, HER2-negative metastatic BC, based on positive outcomes in the phase III OlympiAD trial which showed improved median PFS, response rates, and less toxicity with olaparib compared to SOC.

The purpose of the proposed study is to investigate if the addition of elacestrant to standard olaparib therapy could potentially lead to an improvement in PFS compared to olaparib alone in patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with gBRCA1/2 mutations.

ELEMENT is a phase II, prospective, multi-center, randomized, open label, parallel group study in patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with gBRCA1/2 mutation, with 2:1 randomization into Arm A (olaparib + elacestrant) or arm B (olaparib). Treatment in either arm will be given until disease progression, unacceptable toxicity, withdrawal of patient´s consent to study participation, or end of study.

Study Type

Interventional

Enrollment (Estimated)

176

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Stefan Schoeffel
  • Phone Number: +49 61027480
  • Email: element@gbg.de

Study Contact Backup

  • Name: Laura Steinmann
  • Phone Number: +49 61027480
  • Email: element@gbg.de

Study Locations

  • Germany
      • Bottrop, Germany, 46236
      • Essen, Germany, 45147
        • Recruiting
        • Universitätsklinikum Essen - Klinik für Frauenheilkunde und Geburtshilfe
        • Contact:
      • Heidelberg, Germany, 69120
      • Homburg, Germany, 66424
        • Recruiting
        • Universitätsklinikum des Saarlandes - Frauenklinik
        • Contact:
      • München, Germany, 80634
      • Ravensburg, Germany, 88212
        • Recruiting
        • Studienzentrum Onkologie Ravensburg
        • Principal Investigator:
          • Thomas Decker, Prof. Dr.
        • Contact:
      • Stuttgart, Germany
        • Recruiting
        • Robert Bosch Gesellschaft fuer medizinische Forschung mbH
        • Contact:
      • Worms, Germany, 67550
    • Baden-Wurttemberg
    • Baden-Württembergs
      • Weinheim, Baden-Württembergs, Germany, 69469
        • Recruiting
        • GRN Klinik Weinheim
        • Contact:
    • Bavaria
    • Brandenburg
      • Fürstenwalde, Brandenburg, Germany, 15517
        • Recruiting
        • Schwerpunktpraxis der Gynäkologie und Onkologie
        • Contact:
    • Hesse
      • Frankfurt am Main, Hesse, Germany, 60431
        • Recruiting
        • Agaplesion Frankfurter Diakonie Kliniken gGmbH
        • Principal Investigator:
          • Marc Thill, Prof. Dr.
        • Contact:
      • Frankfurt am Main, Hesse, Germany, 60590
      • Kassel, Hesse, Germany, 34125
        • Recruiting
        • Klinikum Kassel GmbH - Frauenklinik
        • Contact:
      • Wiesbaden, Hesse, Germany, 65189
        • Recruiting
        • St. Josefs-Hospital, Gynäkologie und Geburtshilfe
        • Contact:
    • Lower Saxony
    • North Rhine-Westphalia
      • Cologne, North Rhine-Westphalia, Germany
      • Düsseldorf, North Rhine-Westphalia, Germany, 40225
      • Düsseldorf, North Rhine-Westphalia, Germany, 40235
        • Recruiting
        • Zentrum für Gynäkologische Onkologie am MVZ Medical Center Düsseldorf GmbH
        • Contact:
      • Essen, North Rhine-Westphalia, Germany, 45136
      • Witten, North Rhine-Westphalia, Germany, 58452
      • Wuppertal, North Rhine-Westphalia, Germany, 42283
    • Rhineland-Palatinate
      • Mainz, Rhineland-Palatinate, Germany, 55131
      • Mayen, Rhineland-Palatinate, Germany
        • Recruiting
        • Institut für Versorgungsforschung Mayen
        • Contact:
    • Saarland
      • Saarbrücken, Saarland, Germany, 66113
        • Recruiting
        • Caritas Traegergesellschaft Saarbruecken mbH (CTS)
        • Contact:
    • Saxony
    • State of Berlin
      • Berlin, State of Berlin, Germany, 10367
      • Berlin, State of Berlin, Germany, 12623

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Patients will be eligible for study participation only if they comply with the following criteria:

  1. Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for scheduled visit, the treatment and follow-up, must be obtained and documented according to the local regulatory requirements.
  2. Female or male patients.
  3. Age at study entry of at least 18 years.
  4. Locally advanced or metastatic breast cancer that is HR-positive (ER and/or PgR ≥ 10% of stained cells at IHC) and HER2-negative (IHC 0 or 1+, or 2+ and ISH negative according to ASCO/CAP guidelines).
  5. Patients with deleterious or suspected deleterious gBRCA1/2 mutation detected upon local testing.
  6. Willingness and ability to provide archived formalin fixed paraffin embedded tissue (FFPE) block or a partial block from archived tumor or metastasis.
  7. Indication for standard-of-care PARP inhibitor therapy and planned treatment with olaparib.
  8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2.
  9. Resolution of all acute toxic effects of prior anti-cancer therapy including endocrine therapy or surgical procedures to NCI CTCAE version 5.0 grade ≤ 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion).
  10. Life-expectancy > 6 months.
  11. For female patients: patients of childbearing potential (defined as not post-menopausal and not permanently sterile [latter defined as having undergone hysterectomy, bilateral salpingectomy, or bilateral oophorectomy]) require a negative serum or urinary pregnancy test within 72 hours before starting treatment in this study (in this case, patients need to use highly effective non-hormonal contraceptive methods as specified in the protocol).

For male patients: during the intervention period and for at least 120 days after the last dose of elacestrant, patients should refrain from heterosexual intercourse or use a condom (and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak), and they should refrain from donating sperm.

Exclusion Criteria:

Patients will be ineligible for study participation if they fulfill any of the following criteria:

  1. Known hypersensitivity reaction to one of the compounds, excipients, or substances used in this protocol.
  2. Active or newly diagnosed CNS metastases, including leptomeningeal carcinomatosis, carcinomatous meningitis, or radiographic signs of CNS hemorrhage. Note: Patients with stable brain metastases are allowed. Radiotherapeutic treatment must be completed 1 week before planned day 1 of study therapy.
  3. Presence of symptomatic metastatic visceral disease that are at risk of life-threatening complications in the short term, including but not confined to massive uncontrolled effusions (peritoneal, pleural, pericardial), pulmonary lymphangitis, or fulminant liver involvement.

  4. Inadequate organ function prior to enrolment including:

    • Hemoglobin < 9 g/dL (< 5.6 mmol/L)
    • Absolute neutrophil count (ANC) < 1500/mm³ (< 1.5 x 109/L)
    • Platelets < 100,000/mm³ (< 100 x 109/L)
    • Alanine aminotransferase (ALT/SGPT) and/or aspartate aminotransferase (AST/SGOT) > 3 x upper normal limits (ULN). If the patient has liver metastases, ALT and AST should not be ≥ 5 x ULN.
    • Alkaline phosphatase (ALP) > 2.5 x ULN
    • Total serum bilirubin > 1.5 x ULN (exception: patients with Gilbert's syndrome permitted up to ≤ 3 x ULN)
    • Serum creatinine > 1.5 x ULN or estimated creatinine clearance < 50 mL/min as calculated using the standard method for the institution.
  5. Existing contraindication against the use of the elacestrant or olaparib.
  6. Prior treatment with PARP inhibitors.

  7. Female patients: pregnancy or lactation at the time of randomization or intention to become pregnant during the study and for a predefined period after the end of treatment (as described in protocol).

    Male patients: intention to get a child during the study and for a predefined period after the end of treatment (as described in protocol).

    According to the treatment received during the study, required contraception timelines for female and male patients are described in the study protocol.

  8. Any of the following within 6 months prior to enrolment: myocardial infarction, severe/unstable angina, ongoing grade ≥ 2 cardiac dysrhythmias, prolonged QT corrected by Fridericia's formula (QTcF) grade ≥ 2, uncontrolled atrial fibrillation of any grade, coronary/peripheral artery bypass graft, heart failure of New York Heart Association (NYHA) Class II or greater, or cerebrovascular accident including transient ischemic attack.
  9. Uncontrolled hypertension at the time of screening (systolic BP > 140 mmHg or diastolic BP > 90 mmHg that has not been adequately treated or controlled).
  10. Active and current anticoagulation for treatment purposes of thrombotic events occurring < 6 months before enrolment is not allowed (prophylactic anticoagulation, however, is acceptable). Treatment with an anticoagulant for a thrombotic event occurring > 6 months before enrolment, or for an otherwise stable and allowed medical condition (e.g., well controlled atrial fibrillation) is acceptable, provided dose and coagulation parameters (as defined by local standard of care) are stable for at least 28 days prior to the first dose of study drug.
  11. Known difficulty in tolerating oral medications or conditions which would impair absorption of oral medications such as: uncontrolled nausea or vomiting (i.e., CTCAE ≥ grade 3 despite antiemetic therapy), ongoing gastrointestinal obstruction/motility disorder, malabsorption syndrome, or prior gastric bypass.
  12. History of endometrial intraepithelial neoplasia in patients who have not undergone a hysterectomy.
  13. Malignant disease other than breast cancer, active or being disease-free for less than 5 years (except carcinoma in situ of the cervix, DCIS, and non-melanomatous skin cancer adequately treated).

  14. Uncontrolled significant active infections including HBV, HCV, and/or HIV. Patients with a positive hepatitis B surface antigen result or a positive hepatitis C antibody test result at screening or within 3 months before first dose of study treatment are excluded, except for the following:

    • Participants with positive anti-HBs antibody titer and confirmatory negative hepatitis B DNA polymerase chain reaction.
    • Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled only if they have both completed curative therapy and have a hepatitis C viral load < quantifiable limit.
  15. Any severe, acute, uncontrolled, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational or non-investigational products administration, or may interfere with the interpretation of study results, and, in the judgment of the investigator, would make the patient inappropriate for entry into this study. Moreover, patients who, by virtue of an order issued by judicial or administrative authorities, are committed to an institution or those who cannot take part in clinical trials are excluded from this study.
  16. History of significant neurological or psychiatric disorders including psychotic disorders, dementia, or seizures that would prohibit the understanding and giving of informed consent.
  17. Unable or unwilling to avoid medications, supplements (e.g., St. John's wort), or foods (e.g., grapefruit, pomegranate, pomelos, star fruit, Seville oranges and their juices) that are moderate/strong inhibitors or inducers of CYP3A4 activity. Participation will be allowed if the medication, supplements, or foods are discontinued for at least 14 days prior to study entry and for the duration of the study.
  18. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry.
  19. Receipt of live attenuated vaccination within 30 days prior to study entry. COVID-19 vaccines that do not contain live viruses are allowed (at least one week prior to study entry).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A: Olaparib + elacestrant*

Treatment will be given until disease progression, unacceptable toxicity, withdrawal of patient´s consent to study participation, or end of study.

* Together with GnRH analogue in pre- and perimenopausal women, and in men, at least two weeks prior to treatment.

  • Elacestrant tablets 400 mg orally daily
  • Olaparib 600 mg orally daily The protocol provides procedures for specific adverse events requiring dose modifications or delays.
Drug: Olaparib + Elacestrant
Olaparib 600 mg orally daily and elacestrant 400 mg orally daily
Active Comparator: Arm B: Olaparib

Treatment will be given until disease progression, unacceptable toxicity, withdrawal of patient´s consent to study participation, or end of study.

• Olaparib 600 mg orally once daily

The protocol provides procedures for specific adverse events requiring dose modifications or delays.
Drug: Olaparib
Olaparib 600 mg orally daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival (PFS)
Time Frame: PFS is defined as the time from randomization to first progression as assessed by the investigator, or death, whichever occurs first, assessed up to 48 months.
PFS, investigator-assessed. To evaluate the impact on PFS of elacestrant with olaparib compared to olaparib alone in patients with hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer with gBRCA1/2 mutations.
PFS is defined as the time from randomization to first progression as assessed by the investigator, or death, whichever occurs first, assessed up to 48 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: OS is defined as the time from randomization to death due to any reason, assessed up to 48 months.
To compare OS between treatment arms.
OS is defined as the time from randomization to death due to any reason, assessed up to 48 months.
Patient reported outcome (PRO) in the form of quality of life (QoL) assessment
Time Frame: At baseline, day 1 of cycle 2 (each cycle is 28 days), every 3 months starting from treatment start, and at end of treatment (an average of 12 months per patient).
To assess and compare patient reported breast cancer-specific QoL as measured by FACT-ES questionnaire.
At baseline, day 1 of cycle 2 (each cycle is 28 days), every 3 months starting from treatment start, and at end of treatment (an average of 12 months per patient).
PFS in stratified and exploratory subgroups
Time Frame: PFS is defined as the time from randomization to first progression as assessed by the investigator, or death, whichever occurs first, assessed up to 48 months.

To compare PFS in the stratified subgroups: pre-treatment chemotherapy in the metastatic setting yes vs. no.

To compare PFS in the exploratory subgroups specified in the protocol.
PFS is defined as the time from randomization to first progression as assessed by the investigator, or death, whichever occurs first, assessed up to 48 months.
TTF in the stratified subgroups
Time Frame: TTF is defined as time from randomization to discontinuation of treatment due to disease progression, treatment toxicity, patient´s preference, or death, assessed up to 48 months.

To compare TTF in the stratified subgroups: pre-treatment chemotherapy in the metastatic setting yes vs. no.

To compare TTF in the exploratory subgroups specified in the protocol.
TTF is defined as time from randomization to discontinuation of treatment due to disease progression, treatment toxicity, patient´s preference, or death, assessed up to 48 months.
OS in the stratified subgroups
Time Frame: OS is defined as the time from randomization to death due to any reason, assessed up to 48 months.

To compare OS in the stratified subgroups: pre-treatment chemotherapy in the metastatic setting yes vs. no.

To compare OS in the exploratory subgroups specified in the protocol.
OS is defined as the time from randomization to death due to any reason, assessed up to 48 months.
Overall response rate (ORR)
Time Frame: ORR is defined as the percentage of patients who have achieved either a confirmed complete response or partial response, assessed up to 48 months.
To compare ORR between treatment arms.
ORR is defined as the percentage of patients who have achieved either a confirmed complete response or partial response, assessed up to 48 months.
Clinical benefit rate (CBR)
Time Frame: CBR is defined as the percentage of patients who have achieved either a confirmed complete response or partial response, or stable disease for at least 24 weeks from randomization.
To compare the CBR between treatment arms.
CBR is defined as the percentage of patients who have achieved either a confirmed complete response or partial response, or stable disease for at least 24 weeks from randomization.
Numbers and types of adverse events as assessed by CTCAE v5.0
Time Frame: During treatment phase, an average of 12 months per patient.
To assess and compare safety between treatment arms (frequency and severity of AEs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0).
During treatment phase, an average of 12 months per patient.
Compliance between treatment arms as assessed by treatment delays, reductions, and interruptions
Time Frame: During treatment phase, an average of 12 months per patient.
Frequencies of patients whose treatment had to be reduced, delayed, interrupted, or prematurely discontinued will be reported for both arms, together with reasons for such modifications, and comparisons between the two arms will be conducted with the χ2-test with continuity correction.
During treatment phase, an average of 12 months per patient.
Time-to-treatment failure (TTF)
Time Frame: TTF is defined as time from randomization to discontinuation of treatment due to disease progression, treatment toxicity, patient´s preference, or death, assessed up to 48 months.
To compare TTF between treatment arms (i.e., elacestrant + olaparib vs. olaparib).
TTF is defined as time from randomization to discontinuation of treatment due to disease progression, treatment toxicity, patient´s preference, or death, assessed up to 48 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

GBG Forschungs GmbH

Collaborators

Stemline Therapeutics, Inc.

Investigators

  • Study Chair: Sibylle Loibl, MD, PhD, Prof., MD ASCO, ESGO, ESMO, DKG, DGGG, AGO, DGS, BIG, BCIRG, St. Gallen Faculty Member, SABCS Faculty member

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 13, 2024

Primary Completion (Estimated)

December 31, 2028

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

December 7, 2023

First Submitted That Met QC Criteria

December 29, 2023

First Posted (Actual)

January 11, 2024

Study Record Updates

Last Update Posted (Actual)

December 1, 2025

Last Update Submitted That Met QC Criteria

November 24, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ELEMENT GBG-114

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data that underlie the results reported in this article can be made available after final analysis and publication of all secondary efficacy endpoints.

IPD Sharing Time Frame

Beginning after final analysis and publication of all secondary efficacy endpoints; no end date.

IPD Sharing Access Criteria

Who: Researchers who provide translational research proposals. Proposals should be approved by the GBG scientific board.

What: Individual participant data that underlie the results reported in this article, after final analysis and publication of all secondary efficacy endpoints.

How: Proposal forms should be requested from trafo@gbg.de; once the application has been approved and a data transfer agreement has been signed, researchers will be given access to the data.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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