Elacestrant in Advanced Triple Positive Breast Cancer

Elacestrant in Advanced Triple Positive Breast Cancer, a Phase II Evaluation (ELATE)

The purpose of this study to assess the safety and efficacy of elacestrant, a selective estrogen receptor degrader (SERD) and dual biologic therapy, trastuzumab and pertuzumab, in patients with triple-positive breast cancer with and without an ESR1 mutation.

Study Overview

• Status: Recruiting
• Conditions: ER Positive, HER2 Positive Breast Cancer
• Intervention / Treatment: Drug: Elacestrant; Drug: Trastuzumab; Drug: Pertuzumab

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Adriana Borges-Uba; Phone Number: 646-754-7147; Email: Adriana.borges-uba@nyulangone.org
• Study Contact Backup: Name: Ethel Yepes; Phone Number: 212-263-4402; Email: Ethel.yepes@nyulangone.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Female patients aged 18 years or older.
2. Should be able to provide the informed consent.
3. Histologically confirmed diagnosis of triple-positive breast cancer (ER+, PR+, HER2+). In the study, ER status will be considered positive if ≥10% of tumor cells demonstrate positive nuclear staining by immunohistochemistry, with PR>1%. Patients may be considered to be enrolled on study with prior approval of study PI if ER >10% and without PGR positivity HER2 status will be considered positive with the score of 3+ with immunohistochemistry staining or 2+ by immunohistochemistry and FISH -amplified as per ASCO CAP guidelines (2023)"
4. Disease progression on or after at least one line of NCCN recommended prior therapy
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

6. Patient has adequate organ function, as defined by the following laboratory values:

   1. Hematologic Value:
   2. Hemoglobin ≥9.0 g/dL, without transfusion or growth factors within 1 week
   3. Neutrophils ≥1.5×103/μL or ≥1.0×103/μL for participants with benign ethnic neutropenia
   4. Platelets ≥100×103/μL
   5. Patient must have a baseline LVEF ≥50 % or ≥ institutional LLN within 28 days prior to the study treatment.

7. Sex and Contraceptive/Barrier Requirements

   1. While on study treatment a participant must not breastfeed or be pregnant
   2. Have a negative highly sensitive (eg, beta-human chorionic gonadotropin [β-hCG]) pregnancy test at screening and agree to further pregnancy tests per the protocol.
   3. Practice at least 1 highly effective method of contraception; if oral contraceptives are used, a barrier method of contraception must also be used.
   4. Female participants (pre- or perimenopausal) must use the appropriate highly effective, non-hormonal contraception method within 28 days of the first dose of study treatment, until 7 months after the last dose of study treatment (or longer based on companion drug). Highly effective methods of contraception are those methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include:

   i. intrauterine device (IUD) ii. bilateral tubal occlusion iii. vasectomized partner iv. sexual abstinence (i.e., refraining from heterosexual intercourse during the study treatment and 120 days after the last dose of study treatment).

   e. Unacceptable contraception methods: Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea methods are not acceptable methods of contraception. Female condom and male condom should not be used together.

Exclusion Criteria:

1. Prior treatment with a SERD.
2. Prior treatment with more than two lines of chemotherapy for metastatic disease, including antibody drug conjugates.
3. Untreated and/or active CNS metastases.
4. History of other malignancies within the past 5 years (except adequately treated non-melanoma skin cancer or carcinoma in situ of the cervix).
5. Inability to take oral medications, refractory or chronic nausea, gastrointestinal conditions (including significant gastric or bowel resection), history of malabsorption syndrome, or any other uncontrolled gastrointestinal condition that impact the absorption of the study drug
6. Known intolerance to elacestrant or any of its excipients

7. Uncontrolled active infection or intercurrent illness.

   1. Patients with known HBV and/or HCV infection must have undetectable viral load during screening (See Appendix B).
   2. Patients known to be HIV+ are allowed if they have undetectable viral load at baseline.
8. Patients who are on any of the prohibited medications listed in sections 7.6 and 7.4.
9. Male participants will not be included because Male breast cancer is rare and may differ biologically and hormonally, which would introduce heterogeneity difficult to address in a small, single arm phase II trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Estrogen Receptor 1 (ESR1) wild-type (WT); Trastuzumab and pertuzumab and Elacestrant will be administered until disease progression, unacceptable toxicity or as per PI's decision	Drug: Elacestrant; Elacestrant will be administered orally once daily at a dose of 345 mg daily.; Drug: Trastuzumab; Initial dose of trastuzumab is 8 mg/kg administered as a 90-minute intravenous infusion, followed every 3 weeks thereafter by a dose of 6 mg/kg administered as an intravenous infusion over 30 to 90 minutes.; Drug: Pertuzumab; The initial dose of PERJETA is 840 mg administered as a 60-minute intravenous infusion, followed every 3 weeks thereafter by a dose of 420 mg administered as an intravenous infusion over 30 to 60 minutes.
Experimental: ESR1 Mutated; Trastuzumab and pertuzumab and Elacestrant will be administered until disease progression, unacceptable toxicity or as per PI's decision	Drug: Elacestrant; Elacestrant will be administered orally once daily at a dose of 345 mg daily.; Drug: Trastuzumab; Initial dose of trastuzumab is 8 mg/kg administered as a 90-minute intravenous infusion, followed every 3 weeks thereafter by a dose of 6 mg/kg administered as an intravenous infusion over 30 to 90 minutes.; Drug: Pertuzumab; The initial dose of PERJETA is 840 mg administered as a 60-minute intravenous infusion, followed every 3 weeks thereafter by a dose of 420 mg administered as an intravenous infusion over 30 to 60 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median progression-free survival	Progression-free survival will be measured as the time from the date of first dose to the date of first radiological documentation of disease progression or death, whichever occurs first.	From the date of first dose to the date of first radiological documentation of disease progression or death, whichever occurs first (up to 2 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Overall response rate, defined as the percentage of patients who achieve a Best Overall Response (BOR) of confirmed partial response (PR) or complete response (CR).	End of treatment (up to 2 years)
Duration of response (DoR)		Time from the date of first documented CR/PR until the first radiological documentation of disease progression or death, whichever comes first (up to 2 years)
Change in 36-Item Short Form (SF-36) Health Survey	36-Item Short Form (SF-36) Health Survey (Version 2) The physical component summary (PCS) score, derived from the 36-Item Short Form (SF-36) Health Survey (Version 2). The range of the SF-36 PCS is between 0 and 100, where higher scores represent better physical functioning.	Baseline, End of treatment (up to 2 years)
Overall survival (OS)	Overall survival is defined as the time from the date of the first dose to the date of death from any cause.	From the date of the first dose to the date of death from any cause (up to 2 years)

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Douglas K Marks, MD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2030

Study Registration Dates

• First Submitted: May 21, 2026
• First Submitted That Met QC Criteria: May 21, 2026
• First Posted (Actual): May 28, 2026

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: breast cancer; ESR1 mutation; ESR1; triple positive breast cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Trastuzumab; pertuzumab; elacestrant
• Other Study ID Numbers: 25-00779

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The de-identified participant data from the final research dataset will be shared upon reasonable request beginning 9 to 36 months after publication or as required by a condition of awards or supporting agreements, provided the requesting investigator executes a data use agreement with NYU Langone Health. This instance of data sharing will also require separate IRB review as well as review from NYU Langone's Data Sharing Strategy Board (DSSB). Requests should be directed to: Douglas.Marks@nyulangone.org. The protocol and statistical analysis plan will be posted on Clinicaltrials.gov only as required by federal regulation or supporting awards and agreements.
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• IPD Sharing Access Criteria: The investigator who proposed to use the data will be granted access upon reasonable request. Requests should be directed to Douglas.Marks@nyulangone.org. To gain access, data requestors will need to sign a data access agreement. This instance of data sharing will also require separate IRB review as well as review from NYU Langone's DSSB.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No