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ERADICATE: A Phase Ib/II Study of Elacestrant Plus Trastuzumab Deruxtecan in Patients With CDK4/6 Inhibitor and Endocrine-resistant HR+/HER2-low or HER2-ultralow Metastatic Breast Cancer | Clinical Trials | Clareo Health

NOT_YET_RECRUITINGPHASE1/PHASE2

ERADICATE: A Phase Ib/II Study of Elacestrant Plus Trastuzumab Deruxtecan in Patients With CDK4/6 Inhibitor and Endocrine-resistant HR+/HER2-low or HER2-ultralow Metastatic Breast Cancer

NCT07198724•Sarah Sammons, MD

View on ClinicalTrials.gov

Summary

The goal of this study is to evaluate the safety and efficacy of elacestrant in combination with trastuzumab deruxtecan (T-DXd) in participants with hormone receptor-positive (HR+), HER2-low or HER2-ultralow, metastatic breast cancer that is resistant to prior CDK4/6 inhibitor and endocrine therapy. The names of the study drugs involved in this study are: * Elacestrant (a type of selective estrogen receptor degrader) * Trastuzumab deruxtecan (a type of standard of care antibody drug conjugate)

Detailed Description

This phase Ib/II, open-label, single-arm, investigator-initiated study is to evaluate the safety and efficacy of elacestrant in combination with trastuzumab deruxtecan (T-DXd) in participants with hormone receptor-positive (HR+), HER2-low or HER2-ultralow, metastatic breast cancer that is resistant to prior CDK4/6 inhibitor and endocrine therapy. This is a Phase I/II clinical trial. A Phase I clinical trial tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational dose to use for further studies. "Investigational" means that the drug is being studied. The phase Ib dose-escalation portion of the study is to determine the recommended phase II dose (RP2D) of the Elacestrant in combination with trastuzumab deruxtecan, followed by a phase II expansion to further evaluate efficacy and safety at the RP2D. The research study procedures include screening for eligibility, in-clinic visits, blood tests, urine tests, Computerized Tomography (CT) scans, Magnetic Resonance Imaging (MRI) scans, electrocardiograms (ECGs), and tumor biopsies. The U.S. Food and Drug Administration (FDA) has not approved Elacestrant for CDK4/6 inhibitor and endocrine-resistant HR+/HER2-low or HER2-ultralow metastatic breast cancer but it has been approved for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. The FDA has approved trastuzumab deruxtecan as a treatment option for CDK4/6 inhibitor and endocrine-resistant HR+/HER2-low or HER2-ultralow metastatic breast cancer. The FDA has not approved the combination of Elacestrant and Trastuzumab deruxtecan for CDK4/6 inhibitor and endocrine-resistant HR+/HER2-low or HER2-ultralow metastatic breast cancer. It is expected that about 65 people will take part in this research study. Stemline-Menarini is supporting this research study by providing the study drug, Elacestrant.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Participants must have a histologically or cytologically confirmed diagnosis of HR+/HER2-low metastatic or unresectable locally advanced breast cancer, defined as ER ≥ 10%, any PR in the most recent sample and HER2-low (IHC 1+ or IHC 2+ and ISH non-amplified) or HER2-ultralow (IHC 0 and any membranous staining on any prior sample). Cutoff values for positive/negative HER2 staining should be in accordance with current ASCO/CAP (American Society of Clinical Oncology/College of American Pathologists) guidelines.76 Participants without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiographic evaluation.
•Participants must have had prior CDK4/6 inhibitor and either:
•* Disease progression on or within 12 months of endocrine therapy plus a CDK4/6 inhibitor in the adjuvant setting
•* One previous line of endocrine therapy in metastatic setting if disease progression within 6 months of first-line CDK4/6 plus endocrine treatment for metastatic disease or disease recurrence within 24 months after initiation of adjuvant endocrine therapy
•* Two previous lines of endocrine therapy in the metastatic with or without a targeted therapy (such as but not limited to CDK4/6, mTOR, or PI3K inhibitors) administered for the treatment of metastatic disease.
•* Of note with regards to the 2 lines of previous endocrine therapy requirement:- Disease recurrence while on the first 24 months of adjuvant endocrine therapy will be considered a line of therapy; these patients will only require 1 line of endocrine therapy in the metastatic setting.
•* Single-agent PARP inhibitor therapy is not considered a line of endocrine therapy but is allowed.
•* Changes in dosing schedules, or discontinuations/restarting of the same drugs of the addition of a targeted therapy to an endocrine therapy without progression (e.g., adding a CDK4/6 inhibitor to a current aromatase inhibitor regimen) will not be considered separate lines of therapy.
•Participants may have not received prior chemotherapy or ADC in the metastatic setting.
•Participants must have measurable disease per RECIST 1.1 criteria. See Section 11 for the definition of measurable disease. Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam. See Section 12 (Measurement of Effect) for the evaluation of measurable disease.
+33 more criteria

Exclusion Criteria

•Prior treatment with an antibody-drug conjugate in any setting.
•Prior treatment with an oral novel estrogen receptor degrader or modulator in the metastatic setting (SERD, SERM, PROTAC, or CERAN). Prior fulvestrant is allowed. A washout period of 7 days is required for any endocrine or targeted therapy.
•Receipt of any other investigational compound or device within 2 weeks of the first dose of treatment in this study.
•History of allergic reactions attributed to compounds of similar chemical or biologic composition to elacestrant or T-DXd.
•History of (non-infectious) pneumonitis that required steroids or current ILD by imaging at screening.
•Patients who are pregnant or breastfeeding, or who expect to become pregnant within the projected duration of the study (starting with the screening visit through 12 months after the last dose of study treatment for participants who have received cyclophosphamide, and for 6 months after the last dose of study treatment for those who have not).
•Patients with a known history of active tuberculosis.
•Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection requiring systemic therapy, clinically significant cardiovascular disease including: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication, uncontrolled diabetes mellitus, gastrointestinal disorders potentially affecting the absorption of elacestrant, inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or total gastric resection, or psychiatric illness/social situations that would limit compliance with study requirements. Active hepatitis B or active hepatitis C infection. Ability to comply with study requirements is to be assessed by each investigator at the time of screening for study participation.

Locations (2)

Brigham and Women's Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Key Dates

Start Date

March 1, 2026

Primary Completion Date

June 1, 2028

Completion Date

June 1, 2038

Last Updated

November 5, 2025

Enrollment

ESTIMATED participants

Conditions

Metastatic Breast CancerHER2 Low Breast CarcinomaHER2-negative Breast CancerBreast CancerBreast Cancer Female

Interventions

Elacestrant

DRUG

Trastuzumab Deruxtecan

DRUG

Contacts

Sarah Sammons, MD

CONTACT

617-362-3800 Sara_Sammons@dfci.harvard.edu

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: November 5, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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ERADICATE: A Phase Ib/II Study of Elacestrant Plus Trastuzumab Deruxtecan in Patients With CDK4/6 Inhibitor and Endocrine-resistant HR+/HER2-low or HER2-ultralow Metastatic Breast Cancer

Inclusion Criteria

Exclusion Criteria

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