HER2-negative Breast CancerENCORENCT06774027
Prospective Registry of ADC as First- and Second-line Treatment for Breast Cancer
An observational study of HER2-negative Breast Cancer and HER2 Negative Breast Carcinoma, run by University of California, San Francisco at 3 sites in United States.
Trial summary
Antibody-drug conjugates (ADCs) have demonstrated substantial improvement in progression free survival (PFS) and overall survival (OS) in phase III clinical trials in patients with metastatic triple negative breast cancer (mTNBC) and hormone receptor positive/HER2 negative (HR+/HER2-) metastatic breast cancer (MBC)… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- HER2-negative Breast Cancer, HER2 Negative Breast Carcinoma, Metastatic Breast Cancer
- What is being tested?
- Specimen collection, Non-Investigational Antibody-Drug Conjugates (ADC) and Medical Record Review
- Type of treatment
- Surgery or procedure
- How many people
- 100 participants
- Where
- 3 sitesUnited States
- Study dates
- 8 Oct 2025to 31 Dec 2030
- How long will I take part?
- 5 Years
- Phase
- Observational
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
- Healthy volunteers accepted
- Adult, Older adult
Study population: Adults receiving routine treatment for metastatic breast cancer who have planned, usual care with first line or second line of ADC.
Who may be able to join
- Male or female patients aged 18 years or greater with ability to provide written informed consent for this prospective registry study.
- Estimated life expectancy of at least at 3 months per investigator assessment.
- Willingness to provide an archival tissue sample and blood samples (20cc research blood collection at several timepoints) for research purposes.
- Cohort-specific enrollment criteria:
- Cohort 1: Histologically documented HR+/HER2- MBC with plan to start an FDA-approved ADC as their first ADC per standard of care (SOC).
- Cohort 2: Histologically documented metastatic TNBC with plan to start an FDA-approved ADC as their first ADC per standard of care
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- Cohort 3: Histologically documented HR+/HER2- MBC with plan to start an FDA-approved ADC as their second ADC per standard of care (ADC1 should be an approved ADC administered per SOC or as monotherapy in a clinical trial; no prior experimental ADCs allowed). Clinical data from the first ADC must be available for retrospective review.
- Cohort 4: Histologically documented metastatic TNBC with plan to start an FDA-approved ADC as their second ADC per standard of care (ADC1 should be an approved ADC administered per standard of care or as monotherapy in a clinical trial; no prior experimental ADCs allowed). Clinical data from the first ADC must be available for retrospective review.
- Measurable disease is not required for any cohort.
Who cannot join
- Prior receipt of an experimental ADC in the metastatic setting. Of note, patients who received an FDA-approved ADC as their first ADC (as monotherapy, not in combination) can participate in cohorts 3 or 4 prior to starting their second FDA-approved ADC per standard of care. Of note, for all cohorts, experimental therapies are not allowed as intervening therapies after starting ADC1. If a patient enrolls on a clinical trial of an experimental therapy after ADC1, they will be taken off study.
- Current participation in a clinical trial with an ADC.
- Contraindication to research phlebotomy to collect ~20cc blood at each research blood draw timepoint.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Recruiting
Duke Cancer Institute
Durham, North Carolina, 27708
Anisha Roselin, 919-660-1278, breastcl@duke.edu
Neha Verma, MD
- Recruiting
University of California, San Francisco
San Francisco, California, 94143
Amy Langdon, 415-353-7288, Amy.Deluca@ucsf.edu
877-827-3222, cancertrials@ucsf.edu
- Recruiting
Montefiore Einstein Comprehensive Cancer Center
The Bronx, New York, 10476
Jesus Anampa, MD, janampa@montefiore.org
Jesus D Anampa Mesias, MD, MS
About this study
Official title: ENCORE: Multicenter ProspectivE Registry of Sequential ANtibody Drug COnjugates (ADCs) in HER2 Negative Metastatic BREast Cancer (MBC)
Antibody-drug conjugates (ADCs) have demonstrated substantial improvement in progression free survival (PFS) and overall survival (OS) in phase III clinical trials in patients with metastatic triple negative breast cancer (mTNBC) and hormone receptor positive/HER2 negative (HR+/HER2-) metastatic breast cancer (MBC), offering an effective new treatment strategy. Several outstanding questions drive the decision to use ADC drugs clinically. This is a prospective, multi-site observational study of patients with metastatic breast cancer (mBC) who are being treated with FDA-approved antibody drug conjugates (ADCs) as part of routine care and aims to collect real-world data to evaluate the impact of ADC treatment as part of routine care.
Read the detailed description
PRIMARY OBJECTIVES:
- Real-world progression free survival (rwPFS) of the first line of ADC under routine care (ADC1) by investigator assessment II. Real-world progression free survival (rwPFS) of the second line ADC under routine care (ADC2) by investigator assessment
SECONDARY OBJECTIVES:
- To evaluate the efficacy of ADC1 and ADC2 as measured by duration of response (DOR), best overall response (BOR), disease control rate (DCR), and overall survival (OS) for each ADC.
II. To evaluate key safety parameters for ADC1 and ADC2 by chart review.
EXPLORATORY OBJECTIVES:
- To evaluate/identify correlative biomarkers (e.g., circulating tumor DNA (ctDNA), circulating tumor cells (CTC), and tissue spatial correlates) of response/resistance to ADCs.
II. To evaluate patient reported outcomes (PROs) for each ADC.
OUTLINE:
Participants will have medical chart reviews and biospecimens collected for the duration of routine care with ADC1 and/or ADC2. After the last dose of ADC2, participants will continue to be followed for survival data collection via chart review every 12 weeks for up to 2 years.
- Conditions
- HER2-negative Breast Cancer, HER2 Negative Breast Carcinoma, Metastatic Breast Cancer, HR+ HER2 Breast Cancer, Metastatic Triple Negative Breast Cancers, Metastatic Triple-Negative Breast Carcinoma
- Being tested
- Specimen collection, Non-Investigational Antibody-Drug Conjugates (ADC), Medical Record Review
- 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.
Specimen collectionProcedure or surgery
Also called Biospecimen collection
Blood specimens will be collected during regular clinical visits for correlative and exploratory analysis
Non-Investigational Antibody-Drug Conjugates (ADC)Drug
Also called Non-Investigational ADC
ADC given under usual care for the treatment of cancer
Medical Record ReviewOther
Also called Medical Chart Review
Prospective and retrospective medical chart reviews will be conducted to obtain data for analysis.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: HR+/HER2- mBC participants enrolled before first line ADC (ADC1)) | Participants with histologically documented HR+/HER2- MBC with a plan to start an FDA-approved ADC as a first ADC per usual care will be enrolled before beginning any ADC. Participants will have blood samples obtained during routine clinical visits during ADC1 and ADC2, if applicable. Receives: Procedure: Specimen collection; Drug: Non-Investigational Antibody-Drug Conjugates (ADC); Other: Medical Record Review | |
| Cohort 2: Metastatic Triple Negative Breast Cancer (mTNBC) participants enrolled before ADC1 | Participants with histologically documented metastatic TNBC with a plan to start an FDA-approved ADC as their first ADC per usual care will be enrolled before beginning any ADC. Participants will have blood samples obtained during routine clinical visits during ADC1 and ADC2, if applicable. Receives: Procedure: Specimen collection; Drug: Non-Investigational Antibody-Drug Conjugates (ADC); Other: Medical Record Review | |
| Cohort 3: HR+/HER2- mBC Participants enrolled before second line ADC (ADC2)) | Participants with histologically documented HR+/HER2- MBC with plan to start an FDA-approved ADC as their second ADC per usual care (ADC1 should be an approved ADC administered per usual care or as monotherapy in a clinical trial; no prior experimental ADCs allowed). Clinical data from the first ADC must be available for retrospective review. Participants will have blood samples obtained during routine clinical visits during treatment of cancer with ADC2. Receives: Procedure: Specimen collection; Drug: Non-Investigational Antibody-Drug Conjugates (ADC); Other: Medical Record Review | |
| Cohort 4: mTNBC participants enrolled before ADC2 | Participants with histologically documented metastatic TNBC with plan to start an FDA-approved ADC as their second ADC per usual care (ADC1 should be an approved ADC administered per usual care or as monotherapy in a clinical trial; no prior experimental ADCs allowed). Clinical data from the first ADC must be available for retrospective review. Participants will have blood samples obtained during routine clinical visits during treatment of cancer with ADC2. Receives: Procedure: Specimen collection; Drug: Non-Investigational Antibody-Drug Conjugates (ADC); Other: Medical Record Review |
What is being measured
The primary outcome is the main question the study is designed to answer.
Real-world progression free survival (rwPFS) of first line ADC (ADC1)
rwPFS is defined as the amount of time that elapses between the initiation of ADC1 therapy until the patient experiences disease progression, initiates subsequent anti-cancer therapy, completes study participation, or experiences death from any cause (whichever comes first).
Measured: Up to 5 years
rwPFS of second line ADC (ADC2)
rwPFS is defined as the amount of time that elapses between the initiation of ADC2 therapy following a previous line of ADC (ADC1) until the participant experiences disease progression, initiates subsequent anti-cancer therapy, completes study participation, or experiences death from any cause (whichever comes first).
Measured: Up to 5 years
Secondary outcomes (6)
Median Duration of Response (DOR)
DOR is defined as the amount of time between when measurement criteria are met for complete response (CR) or partial response (PR), whichever is first recorded, until the first date that recurrent or progressive disease (PD) is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the usual care ADC began) per Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The participants response will depend on the achievement of both measurement and confirmation criteria.
Measured: Up to 5 years
Best Overall Response (BOR)
The best overall response is the best response recorded from the start of ADC usual care treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The proportion of participants who experience each the following as a best response to usual care ADC: CR, PR, stable disease (SD), PD or not evaluable (NE) per RECIST 1.1 will be reported. The participants best response will depend on the achievement of both measurement and confirmation criteria
Measured: Up to 5 years
Overall Response Rate (ORR)
The ORR is the best response recorded from the start of ADC usual care treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The proportion of participants who experience either CR or PR during usual care ADC will be reported. The participants response will depend on the achievement of both measurement and confirmation criteria
Measured: Up to 5 years
Disease Control Rate (DCR)
The DCR is defined as the proportion of participants who experience complete response (CR), partial response (PR), or stable disease (SD) per RECIST 1.1 during usual care ADC. The date of first response for either CR, PR, or SD will be used for the calculation of DCR.
Measured: Up to 5 years
Median Real-World Overall Survival Rate (rwOS)
rwOS is defined as the amount of time that elapses between the initiation of usual care ADC and the time of death from any cause, or until the study has completed.
Measured: Up to 5 years
Frequency of usual ADC-related Adverse Events (AEs)
To assess the toxicity profile of each line of usual care ADC, the frequency of key, clinically significant, adverse events by type, grade, ADC line timing, and attribution to each usual care ADC according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be reported.
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 2025
- Study start8 Oct 2025
- Primary completion31 Dec 2030 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2-negative Breast CancerStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
- Target duration
- 5 Years
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Translational Breast Cancer Research Consortium, Gilead Sciences, Johns Hopkins University
- Responsible party
- Sponsor
- Investigators
- Laura Huppert, MD,BA, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06774027
- Sponsor's protocol ID
- 247516
- Other IDs
- TBCRC 067, NCI-2026-07564
- Acronym
- ENCORE
- Status last verified
- Oct 2026
- First submitted
- 8 Jan 2025
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified study data will be shared with research collaborators during the course of the study.