Metastatic Breast CancerPhase 1/2ERADICATENCT07198724
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
A Phase 1/2 study testing Elacestrant and Trastuzumab Deruxtecan in people with Metastatic Breast Cancer and HER2 Low Breast Carcinoma, run by Kristina A. Fanucci at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Breast Cancer, HER2 Low Breast Carcinoma, HER2-negative Breast Cancer
- What is being tested?
- Elacestrant and Trastuzumab Deruxtecan
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Nov 2025to 1 Jun 2038
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 primary or metastatic 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 must have had prior CDK4/6 inhibitor and may have any number of prior endocrine based therapies in the metastatic setting.
- Participants may have progressed on up to 1 prior line of 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.
- Participants must have known ESR1 mutation status in tumor or ctDNA within 6 months of enrollment to the trial. Participants must have Guardant360 CDx testing for ESR1-mutation status if status has not been validated within 60 days of registration.
- Women or men age ≥18 years are eligible.
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- ECOG performance status ≤ 2.
- Participants must have adequate organ and marrow function as defined below:
- Absolute neutrophil count ≥ 1,500/µL
- Platelets ≥ 100,000/µL
- Hemoglobin ≥ 9.0 g/dL
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (or ≤ 2 x ULN in patients with documented Gilbert's syndrome)
- AST(SGOT)/ALT(SGPT) ≤ 2.5 x institutional ULN (or < 5 x ULN in patients with liver metastases)
- Creatinine ≤ 1.5 x institutional ULN OR
- Calculated creatinine clearance ≥ 45 mL/min via the Cockcroft-Gault formula for participants with creatinine levels above institutional ULN
- Baseline LVEF ≥ 50% prior to registration, as measured by echocardiogram (or multiple-gated acquisition [MUGA] scan if an echocardiogram cannot be performed or is inconclusive).
- Participants with a history of central nervous system (CNS) metastases are eligible if: Stable or untreated, asymptomatic brain metastases not needing immediate local therapy. For patients with untreated CNS lesions > 2.0 cm on screening contrast brain MRI, discussion with and approval from the Sponsor Investigator is required prior to enrollment.
- Brain metastases previously treated with local therapy may either be stable since treatment or may have progressed since prior local CNS therapy, provided that there is no clinical indication for immediate re-treatment with local therapy in the opinion of the investigator
- Patients treated with CNS local therapy for newly identified lesions may be eligible to enroll if all of the following criteria are met: Time since WBRT is ≥ 14 days prior to first dose of treatment, time since SRS is ≥ 7 days prior to first dose of treatment, and time since surgical resection is ≥ 14 days
- Postmenopausal women must be postmenopausal, which is defined as any of the following:
- Age ≥ 60 years
- Age < 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) and FSH, and estradiol in the postmenopausal range per local normal range
- Premenopausal women made postmenopausal through the use GnRH agonist prior to study entry are eligible and MUST remain on the GnRH agonist for the duration of protocol treatment.
- Status-post bilateral oophorectomy - After adequate healing post-surgery
- Premenopausal women must have a negative serum or urine pregnancy test. Pregnancy testing does not need to be pursued in female participants who are postmenopausal according to the definition in 3.1.10.
- Women of child-bearing potential and men must agree to use adequate contraception at time of enrollment and for 4 months after the last dose of elacestrant or 7 months after the last dose of trastuzumab deruxtecan, whichever is later.
- Participants must be able to swallow and retain oral medication.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Prior treatment with aatopoisomerase inhibitor 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. A washout period of 14 days is required for any chemotherapy.
- Patients with known brain metastases that are symptomatic or that require therapy for symptom control are not eligible. Patients with stable or asymptomatic brain metastases are allowed. Participants with CNS metastases treated by neurosurgical resection or brain biopsy performed within 4 weeks before day 1 of study therapy will be excluded.
- 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.
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- Patients who are pregnant or breastfeeding, or who expect to become pregnant within the projected duration of the study.
- Patients with 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. Moderate or severe hepatic impairment (Child-Pugh B or C). 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. History of myocardial infarction, acute coronary syndrome or coronary angioplasty/stenting/bypass grafting within the last six months OR congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV or history of CHF NYHA Class III or IV.
- Patients with a history of different malignancy are ineligible, except for those who have been disease-free for at least three years and are deemed by the investigator to be at low risk for recurrence of the prior malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: ductal carcinoma in situ of the breast, cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Kristina Fanucci, MD, 617-362-3800, kristina_fanucci@dfci.harvard.edu
Kristina Fanucci, MD
About this study
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)
Read the 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.
- Conditions
- Metastatic Breast Cancer, HER2 Low Breast Carcinoma, HER2-negative Breast Cancer, Breast Cancer, Breast Cancer Female
- Being tested
- Elacestrant, Trastuzumab Deruxtecan
- Keywords
- Metastatic Breast Cancer, HER2 Low Breast Carcinoma, HER2-negative Breast Cancer, Breast Cancer, Breast Cancer Female, HR+/HER2-low Breast Cancer, HR+/HER2-ultralow Breast Cancer, Endocrine-resistant Breast Cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ElacestrantDrug
Also called Elacestrant dihydrochloride, RAD1901
Selective estrogen receptor degrader (SERD), film-coated tablet, taken orally per protocol.
Trastuzumab DeruxtecanDrug
Also called Fam-Trastuzumab, ENHERTU, DS-8201a, T-DXd
HER2-directed antibody-drug conjugate, vial, via intravenous (into the vein) infusion per standard of care
| Study group | Role | What they receive |
|---|---|---|
| Phase 1b: Elacestrant + Trastuzumab Deruxtecan | Experimental | Up to 28 participants will be enrolled to determine the recommended phase 2 dosage of Elacestrant and will complete the following:
* Baseline visit
* Cycle 1 (21 day cycle)
* Days 1 through 21: Predetermined dose of Elacestrant 1x daily.
* Day 1: Predetermined dose of Trastuzumab Deruxtecan 1x daily.
* Cycle 2 through End of Treatment (21 day cycle):
* Imaging every 9 weeks until Cycle 9, then every 12 weeks
* Day 1: tumor biopsy
* Days 1 through 21: Predetermined dose of Elacestrant 1x daily.
* Day 1: Predetermined dose of Trastuzumab Deruxtecan 1x daily.
* End of Treatment visit with imaging
* Follow up visits every 6 months
* If 3 or less out of 12 participants experience a dose-limiting toxicity (DLT), the recommended Phase II dose of Elacestrant will be that dose level. If there are 4 or more DLTs, Elacestrant dosage will de-escalate and 12 more participants will be enrolled. Receives: Drug: Elacestrant; Drug: Trastuzumab Deruxtecan |
| Phase 2: Elacestrant + Trastuzumab Deruxtecan | Experimental | 37 participants will complete the following:
* Baseline visit
-Cycle 1 (21 day cycle)
* Days 1 through 21: Predetermined dose of Elacestrant 1x daily.
* Day 1: Predetermined dose of Trastuzumab Deruxtecan 1x daily.
-Cycle 2 through End of Treatment (21 day cycle):
* Imaging every 9 weeks until Cycle 9, then every 12 weeks
* Day 1: tumor biopsy
* Days 1 through 21: Predetermined dose of Elacestrant 1x daily.
* Day 1: Predetermined dose of Trastuzumab Deruxtecan 1x daily.
* End of Treatment visit with imaging
* Follow up visits every 6 months Receives: Drug: Elacestrant; Drug: Trastuzumab Deruxtecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended phase II dose (RP2D)
The RP2D is defined as the dose at which ≤ 3 out of 12 participants experience Dose Limiting Toxicities (DLT) during the first treatment cycle.
Measured: Assessed at the end of the first treatment cycle, Day 21.
Objective Response Rate (ORR)
ORR per RECIST 1.1 is defined as the percentage of participants with confirmed complete or partial response as the best overall response.
Measured: assessed for response every 9 weeks (3 cycles) +/- 7 days for the first 27 weeks, then every 12 weeks +/- 7 days, and at end of treatment or start of new anticancer therapy, or up to approximately 24 months
Secondary outcomes (9)
ORR in Participants with ESR1-mutant endocrine- and CDK4/6 inhibitor-resistant HR+/HER2-low or HER2-ultralow metastatic breast cancer
ORR per RECIST 1.1 is defined as the percentage of participants with confirmed complete or partial response as the best overall response.
Measured: assessed for response every 9 weeks (3 cycles) +/- 7 days for the first 27 weeks, then every 12 weeks +/- 7 days, and at end of treatment or start of new anticancer therapy, or up to approximately 24 months
Clinical Benefit Rate (CBR)
CBR per RECIST 1.1 is defined as the percentage of participants with confirmed complete or partial response, or stable disease for ≥ 24 weeks as the best overall response
Measured: assessed for response every 9 weeks (3 cycles) +/- 7 days for the first 27 weeks, then every 12 weeks +/- 7 days, and at end of treatment or start of new anticancer therapy, or up to approximately 24 months
CBR in Participants with ESR1-mutant endocrine- and CDK 4/6 inhibitor-resistant HR+/HER2-low of HER2-ultralow metastatic cancer
CBR per RECIST 1.1 is defined as the percentage of participants with confirmed complete or partial response, or stable disease for ≥ 24 weeks as the best overall response
Measured: assessed for response every 9 weeks (3 cycles) +/- 7 days for the first 27 weeks, then every 12 weeks +/- 7 days, and at end of treatment or start of new anticancer therapy, or up to approximately 24 months
Median progression-free survival (PFS)
PFS is defined as the time from registration to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation.
Measured: assessed for response/progression every 9 weeks (3 cycles) +/- 7 days for the first 27 weeks, then every 12 weeks +/- 7 days, and at end of treatment or start of new anticancer therapy, or up to approximately 36 months
Median PFS in Participants with ESR1-mutant endocrine- and CDK4/6 inhibitor-resistant HR+/HER2-low or HER2-ultralow metastatic breast cancer
PFS is defined as the time from registration to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation.
Measured: assessed for response/progression every 9 weeks (3 cycles) +/- 7 days for the first 27 weeks, then every 12 weeks +/- 7 days, and at end of treatment or start of new anticancer therapy, or up to approximately 36 months
Median Overall Survival (OS)
OS is defined as the time from registration to death due to any cause. Participants still living are censored at the date last known alive.
Measured: assessed at all study visits; once progression is documented, subjects will be followed for survival every 6 months from the time of documented progression until participant withdrawal, death, or removal from study, or up to approximately 36 months
Median OS in Participants with ESR1-mutant endocrine- and CDK4/6 inhibitor-resistant HR+/HER2-low or HER2-ultralow metastatic breast cancer
OS is defined as the time from registration to death due to any cause. Participants still living are censored at the date last known alive.
Measured: assessed at all study visits; once progression is documented, subjects will be followed for survival every 6 months from the time of documented progression until participant withdrawal, death, or removal from study, or up to approximately 36 months
Duration of Response (DOR)
DOR is defined as the time when measurement criteria are met for confirmed complete or partial response (whichever is first recorded) to the first date that recurrent or progressive disease is objectively documented. Participants without response reported are censored at the last disease evaluation.
Measured: assessed for response/progression every 9 weeks (3 cycles) +/- 7 days for the first 27 weeks, then every 12 weeks +/- 7 days, and at end of treatment or start of new anticancer therapy, or up to approximately 36 months
DOR in Participants with ESR1-mutant endocrine- and CDK4/6 inhibitor-resistant HR+/HER2-low or HER2-ultralow metastatic breast cancer
DOR is defined as the time when measurement criteria are met for confirmed complete or partial response (whichever is first recorded) to the first date that recurrent or progressive disease is objectively documented. Participants without response reported are censored at the last disease evaluation.
Measured: assessed for response/progression every 9 weeks (3 cycles) +/- 7 days for the first 27 weeks, then every 12 weeks +/- 7 days, and at end of treatment or start of new anticancer therapy, or up to approximately 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2025
- Study start17 Nov 2025
- Primary completion1 Jun 2028 (estimated)
- Study completion1 Jun 2038 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 65 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kristina A. Fanucci
- Sponsor type
- University, hospital or other
- Collaborators
- Stemline Therapeutics, Inc.
- Responsible party
- Sponsor-investigator, Kristina A. Fanucci, Dana-Farber Cancer Institute
- Investigators
- Kristina Fanucci, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07198724
- Sponsor's protocol ID
- 25-437
- Acronym
- ERADICATE
- Status last verified
- Jun 2026
- First submitted
- 22 Sep 2025
- Last updated
- 10 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07198724
- Acronym / sponsor ID
- ERADICATE / 25-437
- Conditions
- Metastatic Breast Cancer, HER2 Low Breast Carcinoma, HER2-negative Breast Cancer, Breast Cancer, Breast Cancer Female
- Keywords
- Metastatic Breast Cancer, HER2 Low Breast Carcinoma, HER2-negative Breast Cancer, Breast Cancer, Breast Cancer Female, HR+/HER2-low Breast Cancer, HR+/HER2-ultralow Breast Cancer, Endocrine-resistant Breast Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 65 participants (estimated)
- Lead sponsor
- Kristina A. FanucciUniversity, hospital or other
- Collaborators
- Stemline Therapeutics, Inc.
- Study start
- 17 Nov 2025 (actual)
- Primary completion
- 1 Jun 2028 (estimated)
- Study completion
- 1 Jun 2038 (estimated)
- First posted
- 30 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase 1b: Elacestrant + Trastuzumab Deruxtecan | Experimental | Drug: Elacestrant, Drug: Trastuzumab DeruxtecanUp to 28 participants will be enrolled to determine the recommended phase 2 dosage of Elacestrant and will complete the following: * Baseline visit * Cycle 1 (21 day cycle) * Days 1 through 21: Predetermined dose of Elacestrant 1x daily. * Day 1: Predetermined dose of Trastuzumab Deruxtecan 1x daily. * Cycle 2 through End of Treatment (21 day cycle): * Imaging every 9 weeks until Cycle 9, then every 12 weeks * Day 1: tumor biopsy * Days 1 through 21: Predetermined dose of Elacestrant 1x daily. * Day 1: Predetermined dose of Trastuzumab Deruxtecan 1x daily. * End of Treatment visit with imaging * Follow up visits every 6 months * If 3 or less out of 12 participants experience a dose-limiting toxicity (DLT), the recommended Phase II dose of Elacestrant will be that dose level. If there are 4 or more DLTs, Elacestrant dosage will de-escalate and 12 more participants will be enrolled. |
| Phase 2: Elacestrant + Trastuzumab Deruxtecan | Experimental | Drug: Elacestrant, Drug: Trastuzumab Deruxtecan37 participants will complete the following: * Baseline visit -Cycle 1 (21 day cycle) * Days 1 through 21: Predetermined dose of Elacestrant 1x daily. * Day 1: Predetermined dose of Trastuzumab Deruxtecan 1x daily. -Cycle 2 through End of Treatment (21 day cycle): * Imaging every 9 weeks until Cycle 9, then every 12 weeks * Day 1: tumor biopsy * Days 1 through 21: Predetermined dose of Elacestrant 1x daily. * Day 1: Predetermined dose of Trastuzumab Deruxtecan 1x daily. * End of Treatment visit with imaging * Follow up visits every 6 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- 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 primary or metastatic 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 must have had prior CDK4/6 inhibitor and may have any number of prior endocrine based therapies in the metastatic setting.
- Participants may have progressed on up to 1 prior line of 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.
- Participants must have known ESR1 mutation status in tumor or ctDNA within 6 months of enrollment to the trial. Participants must have Guardant360 CDx testing for ESR1-mutation status if status has not been validated within 60 days of registration.
Key exclusion criteria (10 listed)
- Prior treatment with aatopoisomerase inhibitor 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. A washout period of 14 days is required for any chemotherapy.
- Patients with known brain metastases that are symptomatic or that require therapy for symptom control are not eligible. Patients with stable or asymptomatic brain metastases are allowed. Participants with CNS metastases treated by neurosurgical resection or brain biopsy performed within 4 weeks before day 1 of study therapy will be excluded.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ElacestrantAlso: Elacestrant dihydrochloride, RAD1901Selective estrogen receptor degrader (SERD), film-coated tablet, taken orally per protocol. | Drug | Phase 1b: Elacestrant + Trastuzumab Deruxtecan, Phase 2: Elacestrant + Trastuzumab Deruxtecan |
| Trastuzumab DeruxtecanAlso: Fam-Trastuzumab, ENHERTU, DS-8201a, T-DXdHER2-directed antibody-drug conjugate, vial, via intravenous (into the vein) infusion per standard of care | Drug | Phase 1b: Elacestrant + Trastuzumab Deruxtecan, Phase 2: Elacestrant + Trastuzumab Deruxtecan |
Primary outcome
Recommended phase II dose (RP2D)
Time frame: Assessed at the end of the first treatment cycle, Day 21.
The RP2D is defined as the dose at which ≤ 3 out of 12 participants experience Dose Limiting Toxicities (DLT) during the first treatment cycle.
Objective Response Rate (ORR)
Time frame: assessed for response every 9 weeks (3 cycles) +/- 7 days for the first 27 weeks, then every 12 weeks +/- 7 days, and at end of treatment or start of new anticancer therapy, or up to approximately 24 months
ORR per RECIST 1.1 is defined as the percentage of participants with confirmed complete or partial response as the best overall response.
9 secondary outcomes
ORR in Participants with ESR1-mutant endocrine- and CDK4/6 inhibitor-resistant HR+/HER2-low or HER2-ultralow metastatic breast cancer
Time frame: assessed for response every 9 weeks (3 cycles) +/- 7 days for the first 27 weeks, then every 12 weeks +/- 7 days, and at end of treatment or start of new anticancer therapy, or up to approximately 24 months
Clinical Benefit Rate (CBR)
Time frame: assessed for response every 9 weeks (3 cycles) +/- 7 days for the first 27 weeks, then every 12 weeks +/- 7 days, and at end of treatment or start of new anticancer therapy, or up to approximately 24 months
CBR in Participants with ESR1-mutant endocrine- and CDK 4/6 inhibitor-resistant HR+/HER2-low of HER2-ultralow metastatic cancer
Time frame: assessed for response every 9 weeks (3 cycles) +/- 7 days for the first 27 weeks, then every 12 weeks +/- 7 days, and at end of treatment or start of new anticancer therapy, or up to approximately 24 months
Median progression-free survival (PFS)
Time frame: assessed for response/progression every 9 weeks (3 cycles) +/- 7 days for the first 27 weeks, then every 12 weeks +/- 7 days, and at end of treatment or start of new anticancer therapy, or up to approximately 36 months
Median PFS in Participants with ESR1-mutant endocrine- and CDK4/6 inhibitor-resistant HR+/HER2-low or HER2-ultralow metastatic breast cancer
Time frame: assessed for response/progression every 9 weeks (3 cycles) +/- 7 days for the first 27 weeks, then every 12 weeks +/- 7 days, and at end of treatment or start of new anticancer therapy, or up to approximately 36 months
Median Overall Survival (OS)
Time frame: assessed at all study visits; once progression is documented, subjects will be followed for survival every 6 months from the time of documented progression until participant withdrawal, death, or removal from study, or up to approximately 36 months
Median OS in Participants with ESR1-mutant endocrine- and CDK4/6 inhibitor-resistant HR+/HER2-low or HER2-ultralow metastatic breast cancer
Time frame: assessed at all study visits; once progression is documented, subjects will be followed for survival every 6 months from the time of documented progression until participant withdrawal, death, or removal from study, or up to approximately 36 months
Duration of Response (DOR)
Time frame: assessed for response/progression every 9 weeks (3 cycles) +/- 7 days for the first 27 weeks, then every 12 weeks +/- 7 days, and at end of treatment or start of new anticancer therapy, or up to approximately 36 months
DOR in Participants with ESR1-mutant endocrine- and CDK4/6 inhibitor-resistant HR+/HER2-low or HER2-ultralow metastatic breast cancer
Time frame: assessed for response/progression every 9 weeks (3 cycles) +/- 7 days for the first 27 weeks, then every 12 weeks +/- 7 days, and at end of treatment or start of new anticancer therapy, or up to approximately 36 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2026.
- Individual participant dataSharing planned: Yes. The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Kristina Fanucci, MD principal investigator
Dana-Farber Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Elacestrant and Trastuzumab Deruxtecan in people with Metastatic Breast Cancer and HER2 Low Breast Carcinoma, run by Kristina A. Fanucci at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kristina Fanucci, MD (617-362-3800, Kristina_Fanucci@dfci.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recommended phase II dose (RP2D) (time frame: Assessed at the end of the first treatment cycle, Day 21.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2026.