SHR-A1811 Monotherapy or Sequential THPy as Neoadjuvant Therapy for Stage II-III HER2-Positive Breast Cancer

August 24, 2026 updated by: First Affiliated Hospital of Zhejiang University

A Prospective, Multicenter, Exploratory Clinical Study Evaluating the Efficacy and Safety of SHR-A1811 Monotherapy or Sequential THPy as Neoadjuvant Therapy in Stage II-III HER2-positive Breast Cancer

This is a prospective, open-label, phase II, multicenter exploratory clinical study. Eligible female patients aged 18-75 years with stage II-III HER2-positive breast cancer will receive 4 cycles of SHR-A1811 (4.8 mg/kg, intravenous infusion every 3 weeks). After 4 cycles, tumor response will be assessed per RECIST 1.1 criteria. Patients with a ≥50% reduction in tumor burden will continue with another 4 cycles of SHR-A1811 followed by definitive surgery. Patients with <50% reduction will receive 4 cycles of the THPy regimen (docetaxel + trastuzumab + pyrotinib) before surgery. Circulating tumor DNA (ctDNA) will be assessed for minimal residual disease (MRD) at baseline, after 4 cycles of treatment, and postoperatively. The primary endpoint is total pathological complete response (tpCR), assessed by an independent review committee (IRC). This study aims to evaluate the efficacy, safety, and feasibility of imaging- and MRD-guided neoadjuvant therapy in HER2-positive breast cancer.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet 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.
80

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
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310003
        • The First Affiliated Hospital, Zhejiang University School of Medicine
        • Principal Investigator:
          • Peifen Fu
        • Contact:
        • Principal Investigator:
          • Minya Yao

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:

  • Female aged ≥18 years and ≤75 years.
  • Histopathologically confirmed invasive breast cancer with no prior systemic anti-tumor therapy for breast cancer.
  • Histopathologically confirmed HER2-positive status in accordance with the 2018 ASCO-CAP HER2 testing guideline criteria: immunohistochemistry (IHC) score of 3+, or IHC 2+ with positive in situ hybridization (ISH) test (ISH amplification ratio ≥2.0); hormone receptor status must be available.
  • Stage II-III breast cancer per the 8th edition AJCC Breast Cancer Staging System.
  • At least one measurable target lesion according to RECIST Version 1.1.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

  • Adequate function of major organs as defined below (no blood transfusion, granulocyte-stimulating factors or thrombopoietic agents administered within 2 weeks prior to screening):

    1. Hematology: absolute neutrophil count (ANC) >1.5×10⁹/L; platelet count (PLT) >75×10⁹/L; hemoglobin (Hb) >90 g/L.
    2. Serum biochemistry: total bilirubin (TBIL) <1.5×upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <1.5×ULN; alkaline phosphatase <2.5×ULN; blood urea nitrogen (BUN)/urea and creatinine (Cr) <1.5×ULN.
    3. Echocardiogram: left ventricular ejection fraction (LVEF) ≥55%.
    4. 12-lead electrocardiogram: Fridericia-corrected QT interval (QTcF) <470 msec.
  • For premenopausal women of childbearing potential: serum or urine pregnancy test must be negative within 7 days before treatment initiation; not breastfeeding. All participants must use effective barrier contraception throughout treatment and for 6 months after completion of study treatment.
  • Voluntarily provide written informed consent, demonstrate good compliance and willingness to complete scheduled visits and study-related procedures.

Exclusion Criteria:

  • Stage IV breast cancer.
  • Inflammatory breast cancer.
  • Prior anti-tumor therapy or radiotherapy for any malignancy, or concurrent other malignant tumors, except cured carcinoma in situ of cervix, basal cell carcinoma or squamous cell carcinoma.
  • Concurrent receipt of anti-tumor therapy in another clinical trial, including but not limited to chemotherapy, endocrine therapy, biotherapy, bone-modifying agent therapy or immune checkpoint inhibitor therapy.
  • Major surgery unrelated to breast cancer performed within 4 weeks prior to the first dose of study drug, or participants who have not fully recovered from such surgery.

  • Severe cardiac disorders, including but not limited to:

    1. Confirmed history of heart failure or systolic dysfunction (LVEF <50%).
    2. High-risk uncontrolled arrhythmias, such as atrial tachycardia with resting heart rate >100 bpm, significant ventricular arrhythmia (e.g., ventricular tachycardia), or advanced atrioventricular block (Mobitz type II second-degree or third-degree atrioventricular block).
    3. Angina requiring anti-anginal medication.
    4. Electrocardiogram evidence of transmural myocardial infarction.
    5. Poorly controlled hypertension (systolic blood pressure >180 mmHg and/or diastolic blood pressure >100 mmHg) despite medical treatment.
  • Uncontrolled active infection requiring treatment; history of immunodeficiency including positive HIV test, other acquired or congenital immunodeficiency disorders, or history of organ transplantation.
  • Known hypersensitivity to any components of study drugs specified in this protocol.
  • Pregnant or breastfeeding women; women of childbearing potential with positive baseline pregnancy test; women of childbearing potential unwilling to use effective contraception throughout the study and for 6 months after the last study drug administration.
  • Known or suspected interstitial lung disease; moderate to severe pulmonary diseases that may interfere with detection or management of drug-related pulmonary toxicity and severely impair respiratory function within 3 months before the first dose, including but not limited to idiopathic pulmonary fibrosis, organizing pneumonia/bronchiolitis obliterans, pulmonary embolism, severe asthma, severe chronic obstructive pulmonary disease (COPD), obstructive/restrictive lung disease; any autoimmune, connective tissue or inflammatory diseases involving the lung such as rheumatoid arthritis, Sjogren's syndrome, sarcoidosis; or prior history of pneumonectomy.
  • Severe concomitant illnesses or other comorbidities that would interfere with planned treatment, or any other conditions rendering the participant unsuitable for participation in the study as judged by the investigator.

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: N/A
  • Interventional Model: Single Group 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.
Experimental: SHR-A1811 with Response-Guided Therapy
All participants receive an initial 4 cycles of SHR-A1811 (4.8 mg/kg, intravenous infusion every 3 weeks). After 4 cycles, tumor response is assessed per RECIST 1.1 criteria. Participants with ≥50% tumor regression continue with another 4 cycles of SHR-A1811, followed by definitive surgery. Participants with <50% regression switch to 4 cycles of the THPy regimen (docetaxel + trastuzumab + pyrotinib) before surgery. This is a single-arm, non-randomized, open-label, response-guided treatment strategy.
Drug: SHR-A1811
SHR-A1811, 4.8 mg/kg, intravenous infusion once every 3 weeks. All patients receive initial 4 cycles; responders continue additional 4 cycles before surgery.
Drug: THPy
Combined regimen of docetaxel, trastuzumab, and pyrotinib. Administered for 4 cycles to patients with insufficient tumor response after the initial 4 cycles of SHR-A1811 prior to definitive surgery.

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
Time Frame
Rate of total pathological complete response (tpCR)
Time Frame: At the time of definitive surgery (approximately 24 weeks after enrollment)
At the time of definitive surgery (approximately 24 weeks after enrollment)

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
Time Frame
Rate of breast pathological complete response (bpCR)
Time Frame: At the time of definitive surgery (approximately 24 weeks after enrollment)
At the time of definitive surgery (approximately 24 weeks after enrollment)
Objective Response Rate (ORR)
Time Frame: After 2 cycles of study treatment (approximately 6 weeks after enrollment)
After 2 cycles of study treatment (approximately 6 weeks after 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
Time Frame
Incidence and severity of Adverse Events (AEs)
Time Frame: From first study drug administration up to 30 days after the last dose of study treatment
From first study drug administration up to 30 days after the last dose of study treatment

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.
First Affiliated Hospital of Zhejiang 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 (Estimated)

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.
September 1, 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.
April 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.
October 1, 2030

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).
August 24, 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.
August 24, 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.
August 26, 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.
August 26, 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.
August 24, 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.
August 1, 2026

More Information

Terms related to this study

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-ZJ-BC-II-020

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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