Prospective Registry of ADC as First- and Second-line Treatment for Breast Cancer

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
• Interventions: Procedure: Specimen collection; Drug: Non-Investigational Antibody-Drug Conjugates (ADC); Other: Medical Record Review

• Registration Number: NCT06774027
• Lead Sponsor: University of California, San Francisco

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.

Study Timeline

• Study First Submitted: 2025-01-08
• Study First Submitted QC: 2025-01-08
• Study First Posted: 2025-01-14
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-19
• Last Update Posted: 2025-03-20
• Study Start: 2025-04-30
• Primary Completion: 2030-12-31
• Study Completion: 2030-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 100

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Cohort 1: HR+/HER2- mBC participants enrolled before first line ADC (ADC1))	Specimen collection	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.
Cohort 1: HR+/HER2- mBC participants enrolled before first line ADC (ADC1))	Non-Investigational Antibody-Drug Conjugates (ADC)	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.
Cohort 1: HR+/HER2- mBC participants enrolled before first line ADC (ADC1))	Medical Record Review	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.
Cohort 2: Metastatic Triple Negative Breast Cancer (mTNBC) participants enrolled before ADC1	Specimen collection	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.
Cohort 2: Metastatic Triple Negative Breast Cancer (mTNBC) participants enrolled before ADC1	Non-Investigational Antibody-Drug Conjugates (ADC)	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.
Cohort 2: Metastatic Triple Negative Breast Cancer (mTNBC) participants enrolled before ADC1	Medical Record Review	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.
Cohort 3: HR+/HER2- mBC Participants enrolled before second line ADC (ADC2))	Non-Investigational Antibody-Drug Conjugates (ADC)	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.
Cohort 3: HR+/HER2- mBC Participants enrolled before second line ADC (ADC2))	Medical Record Review	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.
Cohort 4: mTNBC participants enrolled before ADC2	Specimen collection	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.
Cohort 3: HR+/HER2- mBC Participants enrolled before second line ADC (ADC2))	Specimen collection	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.
Cohort 4: mTNBC participants enrolled before ADC2	Non-Investigational Antibody-Drug Conjugates (ADC)	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.
Cohort 4: mTNBC participants enrolled before ADC2	Medical Record Review	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.

Primary Outcome Measures

Name	Time	Method
Real-world progression free survival (rwPFS) of first line ADC (ADC1)	Up to 5 years	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).
rwPFS of second line ADC (ADC2)	Up to 5 years	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).

Secondary Outcome Measures

Name	Time	Method
Median Duration of Response (DOR)	Up to 5 years	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.
Best Overall Response (BOR)	Up to 5 years	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
Overall Response Rate (ORR)	Up to 5 years	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
Disease Control Rate (DCR)	Up to 5 years	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.
Median Real-World Overall Survival Rate (rwOS)	Up to 5 years	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.
Frequency of usual ADC-related Adverse Events (AEs)	Up to 5 years	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.

Trial Locations

Locations (1)

University of California, San Francisco; 🇺🇸 San Francisco, California, United States