Antibody-drug conjugates for first- and second-line treatment of metastatic HER2‑negative and triple‑negative breast cancer

ENCORE: Multicenter ProspectivE Registry of Sequential ANtibody Drug COnjugates (ADCs) in HER2 Negative Metastatic BREast Cancer (MBC)

This prospective registry will collect real-world data to see how FDA-approved antibody-drug conjugates work as first- or second-line treatments for adults with metastatic HER2‑negative or triple-negative breast cancer.

Quick facts

• Study type: Observational
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of California, San Francisco (Academic / other)
• Locations: 1 site (San Francisco, California)
• Trial ID: NCT06774027 on ClinicalTrials.gov

What this trial studies

This is a prospective, multi-site observational registry enrolling adults with metastatic HR+/HER2‑ or triple‑negative breast cancer who are starting an FDA-approved antibody-drug conjugate (ADC) as their first or second ADC under routine care. Researchers will perform medical chart reviews, collect biospecimens (archival tissue and serial blood draws), and record safety and patient-reported outcomes while patients receive ADC1 and/or ADC2. Primary endpoints include real-world progression-free survival for first- and second-line ADCs, with secondary endpoints of duration of response, best overall response, disease control rate, overall survival, and safety by chart review. Exploratory analyses will look for correlative biomarkers such as ctDNA and circulating tumor cells and will follow patients for survival every 12 weeks for up to two years after the last ADC dose.

Who should consider this trial

Good fit: Adults (≥18 years) with histologically documented metastatic HR+/HER2‑ or metastatic triple‑negative breast cancer who plan to start an FDA-approved ADC as their first or second ADC, can provide informed consent, and are willing to provide tissue and blood samples are ideal candidates.

Not a fit: Patients who are not receiving an FDA-approved ADC, who have received prior experimental ADCs, who have a very limited life expectancy (under three months), or who decline tissue/blood sampling are unlikely to benefit from this registry.

Why it matters

Potential benefit: If successful, this registry could help doctors understand how ADCs perform in routine practice and guide treatment and monitoring decisions for patients outside clinical trials.

How similar studies have performed: Randomized phase III trials of specific ADCs have shown meaningful improvements in progression-free and overall survival in mTNBC and HR+/HER2‑ metastatic breast cancer, though prospective real-world registries like this are less common.

Eligibility criteria

Inclusion Criteria:

1. Male or female patients aged 18 years or greater with ability to provide written informed consent for this prospective registry study.
2. Estimated life expectancy of at least at 3 months per investigator assessment.
3. Willingness to provide an archival tissue sample and blood samples (20cc research blood collection at several timepoints) for research purposes.
4. 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
   * 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.

Exclusion Criteria:

1. 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.
2. Current participation in a clinical trial with an ADC.
3. Contraindication to research phlebotomy to collect \~20cc blood at each research blood draw timepoint.

Where this trial is running

San Francisco, California

• University of California, San Francisco — San Francisco, California, United States (Recruiting)

Study contacts

• Principal investigator: Laura Huppert, MD,BA — University of California, San Francisco
• Study coordinator: Amy Langdon

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