Clinical trial NCT06774027: Prospective Registry of ADC as First- and Second-line Treatment for Breast Cancer
Official title: ENCORE: Multicenter ProspectivE Registry of Sequential ANtibody Drug COnjugates (ADCs) in HER2 Negative Metastatic BREast Cancer (MBC)
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
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
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Translational Breast Cancer Research Consortium
name: Gilead Sciences
name: Johns Hopkins University
First posted: 2025-01-14
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adults receiving routine treatment for metastatic breast cancer who have planned, usual care with first line or second line of ADC.

Brief 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), 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.

Detailed description: PRIMARY OBJECTIVES:

I. 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:

I. 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:

I. 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.

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.

Primary outcomes:
measure: Real-world progression free survival (rwPFS) of first line ADC (ADC1)
timeFrame: Up to 5 years
measure: rwPFS of second line ADC (ADC2)
timeFrame: Up to 5 years
Secondary outcomes:
measure: Median Duration of Response (DOR)
timeFrame: Up to 5 years
measure: Best Overall Response (BOR)
timeFrame: Up to 5 years
measure: Overall Response Rate (ORR)
timeFrame: Up to 5 years
measure: Disease Control Rate (DCR)
timeFrame: Up to 5 years
measure: Median Real-World Overall Survival Rate (rwOS)
timeFrame: Up to 5 years
measure: Frequency of usual ADC-related Adverse Events (AEs)
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Laura Huppert, MD,BA
role: PRINCIPAL_INVESTIGATOR
References: