Analysis of Exploring Optimized Sequential Treatment Strategies of Antibody-Drug Conjugates (ADCs) in HER2-Low-Expressing Breast Cancer

March 17, 2025 updated by: Yalan Yang, Sun Yat-sen University

A Multi-center, Retrospective, Study on Exploring Optimized Sequential Treatment Strategies of Antibody-Drug Conjugates (ADCs) in HER2-Low-Expressing Breast Cancer

This study retrospectively analyzes the clinical data of HER2-low breast cancer (IHC 1+/2+ and FISH-negative) patients treated with sequential antibody-drug conjugates (ADCs). Key variables include patient demographics, tumor characteristics, ADC regimens (e.g., trastuzumab deruxtecan, sacituzumab govitecan), treatment sequencing, survival outcomes, and safety profiles. Genomic data (e.g., HER2 expression dynamics, TROP2 levels) are integrated to explore resistance mechanisms and prognostic biomarkers.mechanisms.

This study aims to investigate the efficacy of different ADC sequential regimens in HER2-low breast cancer patients.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Breast cancer is one of the most common malignancies in women, posing a significant threat to female health. According to current molecular subtypes, breast cancer is classified into hormone receptor-positive, HER2-positive, and triple-negative breast cancer. However, with the development of novel therapeutic strategies such as antibody-drug conjugates (ADCs), increasing attention has been directed toward HER2-low breast cancer (defined as HER2 immunohistochemistry [IHC] 1+ or 2+/FISH-negative), which accounts for approximately 60%-70% of breast cancer cases. ADCs can exert potential therapeutic effects in HER2-low breast cancer through the "bystander effect" and have been widely adopted in clinical practice. Nevertheless, the optimal sequential treatment strategy for HER2-low patients remains unclear, with a lack of definitive clinical guidelines and limited understanding of resistance mechanisms.

This study aims to investigate the efficacy of different ADC sequential regimens in HER2-low breast cancer patients and explore potential resistance mechanisms. By conducting a retrospective analysis of clinical data from HER2-low patients treated with sequential ADCs, the investigators will evaluate the therapeutic outcomes and safety profiles of various ADC sequencing approaches. Additionally, integrating genomic profiling with routine clinical data, the investigators seek to identify prognostic biomarkers and elucidate resistance pathways. The findings are expected to guide personalized treatment strategies for HER2-low breast cancer patients, ultimately improving clinical outcomes.

Study Type

Observational

Enrollment (Estimated)

700

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Recruiting
        • Sun Yat-sen University Cancer

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients diagnosed with HER2-low breast cancer, defined as immunohistochemistry (IHC) score of 1+ or IHC score of 2+ with negative in situ hybridization (FISH-negative) who received sequential administration of two or more antibody-drug conjugates (ADCs).

Description

Inclusion Criteria:

  • Diagnosed with HER2-low breast cancer, defined as immunohistochemistry (IHC) score of 1+ or IHC score of 2+ with negative in situ hybridization (FISH-negative)
  • Received sequential administration of two or more ADCs
  • Complete data for patient's character, laboratory and imaging test, treatment and follow-up are available.

Exclusion Criteria:

  • Concomitant with other tumor components at the time of diagnosis;
  • Have a history of any other malignant tumors;
  • Lack of complete data

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
First-line Trastuzumab Deruxtecan → Second-line Sacituzumab Govitecan
Other: Non-intervention research
Non-intervention research
First-line Sacituzumab Govitecan → Second-line Trastuzumab Deruxtecan
Other: Non-intervention research
Non-intervention research
First-line RC48 → Second-line Trastuzumab Deruxtecan
Other: Non-intervention research
Non-intervention research
First-line Trastuzumab Deruxtecan → Second-line RC48
Other: Non-intervention research
Non-intervention research
First-line SKB264 → Second-line Trastuzumab Deruxtecan
Other: Non-intervention research
Non-intervention research
First-line Trastuzumab Emtansine → Second-line TQB2102
Other: Non-intervention research
Non-intervention research
First-line TQB2102 → Second-line Trastuzumab Deruxtecan
Other: Non-intervention research
Non-intervention research
First-line RC48 → Second-line TQB2102
Other: Non-intervention research
Non-intervention research

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival
Time Frame: From date of diagnosis until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months.
The length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse.
From date of diagnosis until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: From date of diagnosis until the date of death from any cause, whichever came first, assessed up to 24 months.
The length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that patients diagnosed with the disease are still alive.
From date of diagnosis until the date of death from any cause, whichever came first, assessed up to 24 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2020

Primary Completion (Estimated)

January 1, 2026

Study Completion (Estimated)

January 1, 2026

Study Registration Dates

First Submitted

March 10, 2025

First Submitted That Met QC Criteria

March 10, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 17, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20252696

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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