Trastuzumab Rezetecan Neoadjuvant Therapy in THP-Insensitive HER2-Positive Early Breast Cancer

June 9, 2026 updated by: Hao Zhou, The First Affiliated Hospital of Soochow University

An Interventional, Multicenter Study of Trastuzumab Rezetecan as Neoadjuvant Therapy in Patients With THP-Insensitive HER2-Positive Early Breast Cancer

This study is a response-adapted, multicenter, interventional trial enrolling patients with HER2-positive early or locally advanced breast cancer. All enrolled patients will first receive 2 cycles of standard neoadjuvant THP regimen, consisting of a taxane, trastuzumab, and pertuzumab. After the initial 2-cycle treatment, tumor response will be evaluated by radiologic imaging and patient-derived organoid (PDO) drug sensitivity testing.

Patients with an inadequate response to THP are defined as those with <50% tumor size reduction on imaging, or failure to reach the PDO sensitivity threshold (<80% tumor cell killing for HER2+/HR- tumors; <60% for HER2+/HR+ tumors). These non-responders will switch to receive 4 cycles of trastuzumab rezetecan (SHR-A1811), a novel HER2-targeted antibody-drug conjugate (ADC). Patients with a favorable response (≥50% tumor reduction or meeting the PDO threshold) will continue with an additional 4 cycles of THP.

The primary objective is to evaluate the pathologic complete response (pCR) rate in THP non-responders after switching to trastuzumab rezetecan. Secondary objectives include objective response rate (ORR), event-free survival (EFS), overall survival (OS), 3-year invasive disease-free survival (iDFS), and safety profiles of both treatment strategies. Outcomes in patients who continue THP will be described for exploratory purposes.

A total of 124 patients will be enrolled. This response-adapted, individualized strategy aims to provide an effective option for HER2-positive breast cancer patients with an inadequate early response to conventional THP neoadjuvant therapy.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
124

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

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 Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Jiangsu
      • Suzhou, Jiangsu, China, 215006
        • Recruiting
        • The First Affiliated Hospital of Soochow University

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 1.Age ≥18 years. For premenopausal and perimenopausal patients, a negative pregnancy test is required, and the patient must agree to use effective contraception during treatment.
  • 2.Pathologically confirmed invasive breast cancer, stage II-III according to the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system, with HER2-positive disease defined as: immunohistochemistry (IHC) 3+; or IHC 2+ with confirmed HER2 gene amplification by fluorescence in situ hybridization (FISH).
  • 3.At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
  • 4.No prior chemotherapy, immunotherapy, endocrine therapy, radical surgery, or radiotherapy for breast cancer.
  • 5.Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  • 6.Ability to understand and provide written informed consent.
  • 7.Adequate organ function as evidenced by the following laboratory values:
  • Hemoglobin ≥90 g/L
  • White blood cell count ≥3.5×10⁹/L
  • Platelet count ≥100×10⁹/L
  • Neutrophil count ≥1.5×10⁹/L
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤3× upper limit of normal (ULN)
  • Total bilirubin ≤1.5×ULN
  • Serum creatinine ≤1.5×ULN
  • 8.No evidence of myocardial ischemia on electrocardiogram (ECG); New York Heart Association (NYHA) functional class I; left ventricular ejection fraction (LVEF) ≥55% on echocardiogram; cardiac biomarkers (cardiac troponin I [cTnI] and B-type natriuretic peptide [BNP]) within normal limits.
  • 9.All required baseline laboratory and radiologic examinations completed prior to neoadjuvant therapy.
  • 10.No dysphagia.
  • 11.Availability of complete clinical data.

Exclusion Criteria:

  • 1.Male breast cancer or inflammatory breast cancer.
  • 2.Metastatic breast cancer (Stage IV).
  • 3.Presence of other concurrent malignancies or history of malignancy other than breast cancer within the past 5 years, except for adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
  • 4.Receipt of any other concurrent anti-cancer therapy or participation in another clinical trial.
  • 5.Presence of severe non-malignant disease that would compromise patient compliance or place the patient at unacceptable risk.
  • 6.Major surgical procedure within 4 weeks prior to initiation of study treatment, or anticipated need for major surgery during the study period.
  • 7.Receipt of radiotherapy, chemotherapy, molecular targeted therapy, endocrine therapy, or major breast surgery for breast cancer within 4 weeks prior to study treatment; current or prior use of HER2-targeted monoclonal antibodies, HER2-targeted antibody-drug conjugates (ADCs), or tyrosine kinase inhibitors (TKIs).
  • 8.History of hypersensitivity or contraindication to any component of the study drugs.
  • 9.Poorly controlled cardiac symptoms or diseases, including: New York Heart Association (NYHA) Class II or higher heart failure; unstable angina; myocardial infarction within 1 year; clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention.

Dementia, intellectual disability, or any psychiatric disorder that impairs the ability to understand the informed consent form.

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

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: THP Continuation Arm
All patients first receive 2 cycles of neoadjuvant THP (taxane + trastuzumab + pertuzumab). Patients with favorable response (≥50% tumor reduction or meeting PDO sensitivity threshold) continue with 4 additional cycles of THP.
Drug: THP Regimen (Taxane + Trastuzumab + Pertuzumab)
Neoadjuvant combination therapy consisting of a taxane, trastuzumab, and pertuzumab. Administered as initial treatment to all patients, and continued for responders.
Experimental: SHR-A1811 Switch Arm
All patients first receive 2 cycles of neoadjuvant THP (taxane + trastuzumab + pertuzumab). Patients with inadequate response (<50% tumor reduction or failing PDO sensitivity threshold) switch to 4 cycles of trastuzumab rezetecan (SHR-A1811).
Drug: THP Regimen (Taxane + Trastuzumab + Pertuzumab)
Neoadjuvant combination therapy consisting of a taxane, trastuzumab, and pertuzumab. Administered as initial treatment to all patients, and continued for responders.
Drug: Trastuzumab Rezetecan (SHR-A1811)
HER2-targeted antibody-drug conjugate (ADC). Administered to patients with inadequate response to initial THP therapy.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Pathologic Complete Response (tpCR) Rate
Time Frame: Perioperative
Proportion of patients achieving pathologic complete response (tpCR), defined as the absence of invasive carcinoma in both the breast primary lesion and axillary lymph nodes (ypT0/is ypN0) after neoadjuvant therapy and surgery. Ductal carcinoma in situ (DCIS) is allowed.
Perioperative

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: Up to 24 weeks
Proportion of patients achieving complete response (CR) or partial response (PR) as assessed by the investigator according to RECIST version 1.1 criteria.
Up to 24 weeks
Event-Free Survival (EFS)
Time Frame: From study enrollment up to 3 years after the last patient is enrolled
Time from study enrollment to the first occurrence of invasive disease recurrence (local, regional, or distant), death from any cause, or contralateral invasive breast cancer.
From study enrollment up to 3 years after the last patient is enrolled
Overall Survival (OS)
Time Frame: From study enrollment up to 5 years after the last patient is enrolled
Time from study enrollment to death from any cause.
From study enrollment up to 5 years after the last patient is enrolled
3-Year Invasive Disease-Free Survival (iDFS) Rate
Time Frame: 3 years after study enrollment
Proportion of patients alive and free from invasive breast cancer recurrence (local, regional, or distant) or contralateral invasive breast cancer at 3 years after study enrollment.
3 years after study enrollment

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Safety and Tolerability
Time Frame: From the first dose of study treatment up to 30 days after the last dose
Incidence, nature, and severity of adverse events (AEs), including serious adverse events (SAEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Exposure to study treatment will also be summarized.
From the first dose of study treatment up to 30 days after the last dose

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The First Affiliated Hospital of Soochow University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Zhaoji Guo, The First Affiliated Hospital of Soochow 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 24, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2031

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 3, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 9, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 15, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 15, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 9, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 26-OBU-JS-BC-II-016

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

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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