Breast CancerPhase 2EVOLVE-BDTNCT07340541
Evolutionary Clinical Trial for Novel Biomarker-Driven Therapies
A Phase 2 study testing SERD* + abemaciclib, SERD* + everolimus and SERD* + everolimus or capecitabine in people with Breast Cancer and Metastatic Breast Cancer, run by UNC Lineberger Comprehensive Cancer Center at 6 sites in United States.
Trial summary
This is a multicenter, multi-arm, biomarker-stratified trial designed to evaluate biomarker-directed therapies in patients with estrogen receptor-positive/hormone receptor-negative (ER+/HR-) and triple-negative (TN) metastatic breast cancer (MBC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Metastatic Breast Cancer, Triple Negative Breast Cancer
- What is being tested?
- SERD* + abemaciclib, SERD* + everolimus and SERD* + everolimus or capecitabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 700 participants
- Where
- 6 sitesUnited States
- Study dates
- 16 Feb 2026to 2 Jun 2031
- Phase
- Phase 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
- Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
- Subject is willing and able to comply with study procedures based on the judgement of the investigator.
- Age ≥ 18 years of age at the time of consent
- ECOG Performance Status of 0-2 (see APPENDIX A: ECOG Performance Status Scale).
- Patients must fulfill all eligibility criteria outlined in the LCCC2521 Parent Protocol and consented to LCCC2521 Parent Protocol
Who cannot join
- Inaccessible metastatic lesion to research biopsy
- Subject has already initiated 2nd line therapy
- Concurrent disease or condition that in the opinion of the treating oncologist renders the patient inappropriate for study participation
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Ana Gallegos contact
6 sites in 1 country
United States6 sites, 6 recruiting
- Recruiting
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Cesar Santa-Maria, MD, jhcccro@jhmi.edu
Cesar Santa-Maria, MD
- Recruiting
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, 27599-7305
Lisa A. Carey, MD, 919-966-4431
Lisa A Carey, MD
- Not yet recruiting
Baylor College of Medicine
Houston, Texas, 77030
Ahmed M Elkhanany, MD, 713-798-1630
Ahmed M Elkhanany, MD
- Recruiting
Yale Cancer Center Clinical Trials Office
New Haven, Connecticut, 06519
Sarah Mooney, sarah.mooney@yale.edu
Eric Winer, MD
- Recruiting
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
Amy Clark, MD, amy.clark@uphs.upenn.edu
Amy Clark, MD
- Not yet recruiting
Mayo Clinic
Rochester, Minnesota, 55905
Jen Hager, mayocliniccancerstudies@mayo.edu
Karthik Giridhar, MD
About this study
Official title: TBCRC Evolutionary Clinical Trial for Novel Biomarker-Driven Therapies (EVOLVE-BDT)
This is a multicenter, multi-arm, biomarker-stratified trial designed to evaluate biomarker-directed therapies in patients with estrogen receptor-positive/hormone receptor-negative (ER+/HR-) and triple-negative (TN) metastatic breast cancer (MBC). The trial integrates both retrospective and prospective data collection, including archival tumor tissue, medical record abstraction, and prospective tumor and blood sampling prior to initiation of protocol directed treatment. Based on biomarker subtype, participants will receive standard of care therapy. Liquid biopsy will be collected on Cycle 2 Day 1, and then liquid biopsy, imaging and clinical data will be collected at each re-staging. Treatment will continue until discontinuation for progression, toxicity or at the discretion of the treating physician.
Read the detailed description
The platform design makes it easy to assess multiple targeted therapies at the same time, focusing on patient groups identified by specific biomarkers. Patients who experience disease progression may be reassigned to additional eligible sub trials evaluating alternative therapeutic options. The primary endpoint for each arm is progression-free survival (PFS). This adaptive framework enables continuous learning and rapid translation of biomarker discoveries into therapeutic evaluation, promoting an agile and data-driven approach to treatment optimization in advanced breast cancer.
Beyond ER and HER2, there are few biomarkers to drive treatment decisions in metastatic and primary breast cancer, leaving a gap in effective treatments for other subtypes. To address this, triple-negative (TNBC) is pioneering an adaptive, evolutionary trial focusing on women with metastatic breast cancer (MBC) in the second-line (2L) setting. The adaptive trial infrastructure is designed to serve as an integrated parent study, enabling coordinated acquisition of clinical and translational data, as well as training and testing activities. Within this framework, individual biomarker-driven sub-trials (based on biomarker development) can be created and conducted.
Eligible participants include patients with ER+/HER2- or triple-negative (TNBC) metastatic breast cancer (MBC) who have progressed on first line (1L) therapy but have not yet initiated second-line (2L) treatment. HER2+ patients will be excluded due to the availability of established effective therapies.
This Sub Protocol #1 will enroll subjects based on biomarker subtype. Participants will receive a standard of care therapy. Liquid biopsy will be collected on Cycle 2 Day 1, and then liquid biopsy, imaging and clinical data will be collected at each re-staging. Treatment will continue until discontinuation for progression, toxicity or at the discretion of the treating physician. In order to participate in Sub Protocol #1 subjects must have consented to the Parent protocol.
- Conditions
- Breast Cancer, Metastatic Breast Cancer, Triple Negative Breast Cancer, Estrogen-receptor-positive Breast Cancer, Hormone Receptor Negative Breast Carcinoma
- Being tested
- SERD* + abemaciclib, SERD* + everolimus, SERD* + everolimus or capecitabine, SOC, Antiandrogen
- Keywords
- biomarker directed therapies, biomarker stratified trial
- Medical subject headings
- Breast Neoplasms, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SERD* + abemaciclibDrug
Investigators choice Selective Estrogen Receptor Degrader + abemaciclib therapy.
SERD* + everolimusDrug
Investigators choice Selective Estrogen Receptor Degrader + everolimus therapy.
SERD* + everolimus or capecitabineDrug
Investigators choice Selective Estrogen Receptor Degrader + everolimus or capecitabine therapy.
SOCDrug
standard-of-care (SOC) chemotherapy in breast cancer
AntiandrogenDrug
Antiandrogen therapy
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 Arm A | Experimental | ER+ (Estrogen Receptor Positive) and HER2- (Human Epidermal Growth Factor Receptor 2 Negative). ESR1 mutant positive or negative and Phosphatidylinositol 3-kinase catalytic subunit alpha / AKT serine/threonine kinase / PTEN loss or deletion negative. Receives: Drug: SERD* + abemaciclib |
| Cohort 1- Arm B | Experimental | ER+ (Estrogen Receptor Positive) and HER2- (Human Epidermal Growth Factor Receptor 2 Negative). ESR1 mutant positive or negative and Phosphatidylinositol 3-kinase catalytic subunit alpha / AKT serine/threonine kinase / PTEN loss or deletion negative. Receives: Drug: SERD* + everolimus |
| Cohort 2 Arm A | Experimental | ER+ (Estrogen Receptor Positive) and HER2- (Human Epidermal Growth Factor Receptor 2 Negative). ESR1 mutant negative or positive, and Phosphatidylinositol 3-kinase catalytic subunit alpha / AKT serine/threonine kinase / PTEN loss or deletion positive. Receives: Drug: SERD* + abemaciclib |
| Cohort 2 Arm B | Experimental | ER+ (Estrogen Receptor Positive) and HER2- (Human Epidermal Growth Factor Receptor 2 Negative). ESR1 mutant negative or positive, and Phosphatidylinositol 3-kinase catalytic subunit alpha / AKT serine/threonine kinase / PTEN loss or deletion positive. Receives: Drug: SERD* + everolimus or capecitabine |
| Cohort 3 | Active comparator | Triple-Negative Breast Cancer (TNBC): ER- (Estrogen receptor negative), PR- (Progesterone receptor negative), HER2- HER2 negative. AR - = Androgen Receptor negative, PD-L1 (Programmed Death-Ligand 1) positive or negative. Receives: Drug: SOC |
| Cohort 4 | Experimental | Triple-Negative Breast Cancer (TNBC): ER- (Estrogen receptor negative), PR- (Progesterone receptor negative), HER2- HER2 negative. AR + = Androgen Receptor positive, PD-L1 (Programmed Death-Ligand 1) positive or negative. Receives: Drug: Antiandrogen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intra-Individual Progression-Free Survival (PFS)
Progression-Free Survival (PFS) is defined as the time from initiation of study therapy until documented disease progression per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1 or death from any cause, whichever occurs first. For intra-individual comparisons across successive therapy lines, a PFS ratio will be calculated by dividing the PFS of the current line (nth line, PFSₙ) by the PFS of the preceding line ((n-1)th line, PFSn-1). This allows each patient to serve as their own control, reducing between-patient variability and normalizing for the expected decline in PFS with later lines. RECIST v1.1 defines Complete Response (CR) as disappearance of all target lesions, Partial Response (PR) as ≥30% decrease, Stable Disease (SD) as insufficient change for PR or PD, and Progressive Disease (PD) as ≥20% increase, measurable growth in non-target lesions, or new lesions.
Measured: Up to 5 years
Secondary outcomes (12)
Progression free survival (PFS) - Between-Arm Evaluation
This endpoint assesses between two or more concurrently accruing arms, typically an investigational or biomarker-driven regimen versus a shared control or reference arm. Progression-Free Survival (PFS) is defined as the time from initiation of study therapy until documented disease progression per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1 or death from any cause, whichever occurs first. RECIST v1.1 defines Complete Response (CR) as disappearance of all target lesions, Partial Response (PR) as ≥30% decrease, Stable Disease (SD) as insufficient change for PR or PD, and Progressive Disease (PD) as ≥20% increase, measurable growth in non-target lesions, or new lesions.
Measured: Up to 3 months
Tissue- and blood-based biomarkers on response rate
Tissue- and blood-based biomarkers predictive of response or resistance to standard-of-care first- and second-line therapies will be investigated. Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1 will be used for tumor response assessment. RECIST v1.1 defines Complete Response (CR) as disappearance of all target lesions, Partial Response (PR) as ≥30% decrease, Stable Disease (SD) as insufficient change for PR or PD, and Progressive Disease (PD) as ≥20% increase, measurable growth in non-target lesions, or new lesions.
Measured: Up to 3 months
Overall survival (OS)
Overall survival (OS) is defined as the time from initiation of study therapy to death from any cause.
Measured: Up to 12 months
Objective response rate (ORR)
Objective response rate (ORR) is defined as the proportion of subjects with a complete response or partial response to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST)v1.1. RECIST v1.1 defines Complete Response (CR) as disappearance of all target lesions, Partial Response (PR) as ≥30% decrease, Stable Disease (SD) as insufficient change for PR or PD, and Progressive Disease (PD) as ≥20% increase, measurable growth in non-target lesions, or new lesions.
Measured: Up to 3 months
Duration of response (DoR)
DOR is defined as the time from documentation of PR or better to progressive disease (PD) and will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for each investigational regimen. RECIST v1.1 defines Complete Response (CR) as disappearance of all target lesions, Partial Response (PR) as ≥30% decrease, Stable Disease (SD) as insufficient change for PR or PD, and Progressive Disease (PD) as ≥20% increase, measurable growth in non-target lesions, or new lesions.
Measured: Up to 12 months
Clinical benefit rate (CBR)
Clinical benefit rate (CBR) is defined as the proportion of patients who achieve a complete response (CR), partial response (PR), or stable disease (SD) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. RECIST v1.1 defines Complete Response (CR) as disappearance of all target lesions, Partial Response (PR) as ≥30% decrease, Stable Disease (SD) as insufficient change for PR or PD, and Progressive Disease (PD) as ≥20% increase, measurable growth in non-target lesions, or new lesions. C
Measured: Up to 12 months
Grade 2 or above Adverse Events per NCI Common Terminology Criteria for Adverse Events (CTCAE)
Grade 2 or above treatment attributed Adverse Events per NCI CTCAE will be reported. The NCI CTCAE is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Measured: Up to 12 months
Changes in circulating tumor DNA (ctDNA) levels
Changes in circulating tumor DNA (ctDNA) levels and mutation profiles under therapeutic pressure over time will be assessed. Circulating tumor DNA (ctDNA) mutation profiles during treatment will be assessed via blood draws using the Tempus Xf assay. Detected set of oncogenic drivers, resistance mutations, single nucleotide variants (SNVs), insertions and deletions (INDELs), copy number gains (CNGs) and gene rearrangements will be reported.
Measured: Up to 12 months
Changes in transcriptomic data - tissue
Changes in transcriptomic profiles under therapeutic pressure will be assessed over time. Transcriptomic data from baseline and post-baseline primary or metastatic tumor tissue will be generated using the Tempus XR platform, providing quantitative gene expression levels for each panel gene per sample.
Measured: Up to 12 months
Changes in transcriptomic data - blood
Transcriptomic changes under therapeutic pressure will be assessed over time using evRNA-seq expression levels obtained from blood-derived extracellular vesicles, in patient blood will provide quantitative estimates of gene transcript levels transcriptome-wide.
Measured: Up to 12 months
Changes in Circulating tumor DNA (ctDNA) and tumor response relation
Changes in ctDNA and tumor response relation over time will be assessed. ctDNA will be assessed via blood draws using the Tempus Xf assay and gene rearrangements will be reported. Tumor response will be evaluated at corresponding time points using RECIST v1.1 criteria. RECIST v1.1 defines Complete Response (CR) as disappearance of all target lesions, Partial Response (PR) as ≥30% decrease, Stable Disease (SD) as insufficient change for PR or PD, and Progressive Disease (PD) as ≥20% increase, measurable growth in non-target lesions, or new lesions.
Measured: Up to 12 months
Progression free survival (PFS) -Within Arm Evaluation
This endpoint assesses PFS in a specific treatment arm compared with a prespecified historical control derived from contemporary real-world data or prior clinical trials. Progression-Free Survival (PFS) is defined as the time from initiation of study therapy until documented disease progression per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1 or death from any cause, whichever occurs first. RECIST v1.1 defines Complete Response (CR) as disappearance of all target lesions, Partial Response (PR) as ≥30% decrease, Stable Disease (SD) as insufficient change for PR or PD, and Progressive Disease (PD) as ≥20% increase, measurable growth in non-target lesions, or new lesions.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2026
- Study start16 Feb 2026
- Primary completion2 Jun 2031 (estimated)
- Study completion2 Jun 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Patients are stratified according to tumor marker profiles and receive corresponding treatment regimens.
- Masking
- None (open label)
- Enrolment
- 700 participants (estimated)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Advanced Research Projects Agency for Health (ARPA-H), Breast Cancer Research Foundation, Translational Breast Cancer Research Consortium
- Responsible party
- Sponsor
- Investigators
- Lisa A Carey, MD, Principal investigator, UNC Lineberger Comprehensive Cancer CenterEric Winer, MD, Study chair, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07340541
- Sponsor's protocol ID
- LCCC2521-TBCRC-073(EVOLVE-BDT)
- Other IDs
- 140D042590009
- Acronym
- EVOLVE-BDT
- Status last verified
- Sep 2026
- First submitted
- 12 Jan 2026
- Last updated
- 18 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TBCRC Evolutionary Clinical Trial for Novel Biomarker-Driven Therapies (EVOLVE-BDT)
- ClinicalTrials.gov ID
- NCT07340541
- Acronym / sponsor ID
- EVOLVE-BDT / LCCC2521-TBCRC-073(EVOLVE-BDT)
- Conditions
- Breast Cancer, Metastatic Breast Cancer, Triple Negative Breast Cancer, Estrogen-receptor-positive Breast Cancer, Hormone Receptor Negative Breast Carcinoma
- Keywords
- biomarker directed therapies, biomarker stratified trial
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 700 participants (estimated)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- Advanced Research Projects Agency for Health (ARPA-H), Breast Cancer Research Foundation, Translational Breast Cancer Research Consortium
- Study start
- 16 Feb 2026 (actual)
- Primary completion
- 2 Jun 2031 (estimated)
- Study completion
- 2 Jun 2031 (estimated)
- First posted
- 14 Jan 2026 (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.
This is a multicenter, multi-arm, biomarker-stratified trial designed to evaluate biomarker-directed therapies in patients with estrogen receptor-positive/hormone receptor-negative (ER+/HR-) and triple-negative (TN) metastatic breast cancer (MBC). The trial integrates both retrospective and prospective data collection, including archival tumor tissue, medical record abstraction, and prospective tumor and blood sampling prior to initiation of protocol directed treatment. Based on biomarker subtype, participants will receive standard of care therapy. Liquid biopsy will be collected on Cycle 2 Day 1, and then liquid biopsy, imaging and clinical data will be collected at each re-staging. Treatment will continue until discontinuation for progression, toxicity or at the discretion of the treating physician.
Detailed description
The platform design makes it easy to assess multiple targeted therapies at the same time, focusing on patient groups identified by specific biomarkers. Patients who experience disease progression may be reassigned to additional eligible sub trials evaluating alternative therapeutic options. The primary endpoint for each arm is progression-free survival (PFS). This adaptive framework enables continuous learning and rapid translation of biomarker discoveries into therapeutic evaluation, promoting an agile and data-driven approach to treatment optimization in advanced breast cancer.
Beyond ER and HER2, there are few biomarkers to drive treatment decisions in metastatic and primary breast cancer, leaving a gap in effective treatments for other subtypes. To address this, triple-negative (TNBC) is pioneering an adaptive, evolutionary trial focusing on women with metastatic breast cancer (MBC) in the second-line (2L) setting. The adaptive trial infrastructure is designed to serve as an integrated parent study, enabling coordinated acquisition of clinical and translational data, as well as training and testing activities. Within this framework, individual biomarker-driven sub-trials (based on biomarker development) can be created and conducted.
Eligible participants include patients with ER+/HER2- or triple-negative (TNBC) metastatic breast cancer (MBC) who have progressed on first line (1L) therapy but have not yet initiated second-line (2L) treatment. HER2+ patients will be excluded due to the availability of established effective therapies.
This Sub Protocol #1 will enroll subjects based on biomarker subtype. Participants will receive a standard of care therapy. Liquid biopsy will be collected on Cycle 2 Day 1, and then liquid biopsy, imaging and clinical data will be collected at each re-staging. Treatment will continue until discontinuation for progression, toxicity or at the discretion of the treating physician. In order to participate in Sub Protocol #1 subjects must have consented to the Parent protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
- Model description
- Patients are stratified according to tumor marker profiles and receive corresponding treatment regimens.
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 Arm A | Experimental | Drug: SERD* + abemaciclibER+ (Estrogen Receptor Positive) and HER2- (Human Epidermal Growth Factor Receptor 2 Negative). ESR1 mutant positive or negative and Phosphatidylinositol 3-kinase catalytic subunit alpha / AKT serine/threonine kinase / PTEN loss or deletion negative. |
| Cohort 1- Arm B | Experimental | Drug: SERD* + everolimusER+ (Estrogen Receptor Positive) and HER2- (Human Epidermal Growth Factor Receptor 2 Negative). ESR1 mutant positive or negative and Phosphatidylinositol 3-kinase catalytic subunit alpha / AKT serine/threonine kinase / PTEN loss or deletion negative. |
| Cohort 2 Arm A | Experimental | Drug: SERD* + abemaciclibER+ (Estrogen Receptor Positive) and HER2- (Human Epidermal Growth Factor Receptor 2 Negative). ESR1 mutant negative or positive, and Phosphatidylinositol 3-kinase catalytic subunit alpha / AKT serine/threonine kinase / PTEN loss or deletion positive. |
| Cohort 2 Arm B | Experimental | Drug: SERD* + everolimus or capecitabineER+ (Estrogen Receptor Positive) and HER2- (Human Epidermal Growth Factor Receptor 2 Negative). ESR1 mutant negative or positive, and Phosphatidylinositol 3-kinase catalytic subunit alpha / AKT serine/threonine kinase / PTEN loss or deletion positive. |
| Cohort 3 | Active comparator | Drug: SOCTriple-Negative Breast Cancer (TNBC): ER- (Estrogen receptor negative), PR- (Progesterone receptor negative), HER2- HER2 negative. AR - = Androgen Receptor negative, PD-L1 (Programmed Death-Ligand 1) positive or negative. |
| Cohort 4 | Experimental | Drug: AntiandrogenTriple-Negative Breast Cancer (TNBC): ER- (Estrogen receptor negative), PR- (Progesterone receptor negative), HER2- HER2 negative. AR + = Androgen Receptor positive, PD-L1 (Programmed Death-Ligand 1) positive or negative. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
- Subject is willing and able to comply with study procedures based on the judgement of the investigator.
- Age ≥ 18 years of age at the time of consent
- ECOG Performance Status of 0-2 (see APPENDIX A: ECOG Performance Status Scale).
- Patients must fulfill all eligibility criteria outlined in the LCCC2521 Parent Protocol and consented to LCCC2521 Parent Protocol
Key exclusion criteria (3 listed)
- Inaccessible metastatic lesion to research biopsy
- Subject has already initiated 2nd line therapy
- Concurrent disease or condition that in the opinion of the treating oncologist renders the patient inappropriate for study participation
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 |
|---|---|---|
| SERD* + abemaciclibInvestigators choice Selective Estrogen Receptor Degrader + abemaciclib therapy. | Drug | Cohort 1 Arm A, Cohort 2 Arm A |
| SERD* + everolimusInvestigators choice Selective Estrogen Receptor Degrader + everolimus therapy. | Drug | Cohort 1- Arm B |
| SERD* + everolimus or capecitabineInvestigators choice Selective Estrogen Receptor Degrader + everolimus or capecitabine therapy. | Drug | Cohort 2 Arm B |
| SOCstandard-of-care (SOC) chemotherapy in breast cancer | Drug | Cohort 3 |
| AntiandrogenAntiandrogen therapy | Drug | Cohort 4 |
Primary outcome
Intra-Individual Progression-Free Survival (PFS)
Time frame: Up to 5 years
Progression-Free Survival (PFS) is defined as the time from initiation of study therapy until documented disease progression per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1 or death from any cause, whichever occurs first. For intra-individual comparisons across successive therapy lines, a PFS ratio will be calculated by dividing the PFS of the current line (nth line, PFSₙ) by the PFS of the preceding line ((n-1)th line, PFSn-1). This allows each patient to serve as their own control, reducing between-patient variability and normalizing for the expected decline in PFS with later lines. RECIST v1.1 defines Complete Response (CR) as disappearance of all target lesions, Partial Response (PR) as ≥30% decrease, Stable Disease (SD) as insufficient change for PR or PD, and Progressive Disease (PD) as ≥20% increase, measurable growth in non-target lesions, or new lesions.
12 secondary outcomes
Progression free survival (PFS) - Between-Arm Evaluation
Time frame: Up to 3 months
Tissue- and blood-based biomarkers on response rate
Time frame: Up to 3 months
Overall survival (OS)
Time frame: Up to 12 months
Objective response rate (ORR)
Time frame: Up to 3 months
Duration of response (DoR)
Time frame: Up to 12 months
Clinical benefit rate (CBR)
Time frame: Up to 12 months
Grade 2 or above Adverse Events per NCI Common Terminology Criteria for Adverse Events (CTCAE)
Time frame: Up to 12 months
Changes in circulating tumor DNA (ctDNA) levels
Time frame: Up to 12 months
Changes in transcriptomic data - tissue
Time frame: Up to 12 months
Changes in transcriptomic data - blood
Time frame: Up to 12 months
Changes in Circulating tumor DNA (ctDNA) and tumor response relation
Time frame: Up to 12 months
Progression free survival (PFS) -Within Arm Evaluation
Time frame: Up to 5 years
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 18 Sep 2026.
- University of North Carolina Lineberger Comprehensive Cancer Center Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Ana Gallegos contact
Lisa A Carey, MD principal investigator
UNC Lineberger Comprehensive Cancer Center
Eric Winer, MD study chair
Yale University
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SERD* + abemaciclib, SERD* + everolimus and SERD* + everolimus or capecitabine in people with Breast Cancer and Metastatic Breast Cancer, run by UNC Lineberger Comprehensive Cancer Center at 6 sites 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 5 inclusion and 3 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 18 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites 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 phase mean?
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 Emily L Schworer (919-984-0000, emily_lane@med.unc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intra-Individual Progression-Free Survival (PFS) (time frame: Up to 5 years). 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 18 Sep 2026; AzTrials last refreshed its copy on 26 Oct 2026.