Neoadjuvant SHR-A1811 Combined With Pertuzumab in HER2-Positive Breast Cancer: An Exploratory Clinical Study.

NCT07528898 | Not Yet Recruiting Phase 2

• 1 other identifier: OBU-BC-II-279
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, two-arm, exploratory clinical study designed to evaluate the efficacy and safety of a response-guided neoadjuvant treatment strategy in patients with HER2-positive early or locally advanced breast cancer. Breast cancer is the most common malignancy in women worldwide, and HER2-positive disease accounts for approximately 15-20% of cases and is associated with aggressive tumor biology and a higher risk of recurrence. The introduction of HER2-targeted therapies, including trastuzumab and pertuzumab, has significantly improved patient outcomes. However, a proportion of patients exhibit suboptimal response to standard neoadjuvant therapy, highlighting the need for more effective treatment strategies. In this study, approximately 100 eligible patients will be enrolled. All patients will initially receive 2 cycles of standard neoadjuvant therapy with trastuzumab, pertuzumab, and chemotherapy (THP or TCbHP). Tumor response will be assessed according to RECIST version 1.1 criteria. Patients with tumor reduction greater than 40% will continue the same regimen for an additional 4 cycles. Patients with tumor reduction of 40% or less will switch to an alternative regimen consisting of SHR-A1811, a novel HER2-targeted antibody-drug conjugate, in combination with pertuzumab for 4 cycles. SHR-A1811 is an investigational HER2-targeted antibody-drug conjugate designed to deliver a cytotoxic payload directly to tumor cells, potentially overcoming resistance to prior HER2-targeted therapies. Emerging clinical data have demonstrated promising anti-tumor activity and manageable safety in HER2-positive breast cancer. Clinical data, including baseline characteristics, imaging findings, and pathological markers such as Ki-67, will be collected throughout the study. Efficacy will be evaluated based on imaging assessments according to RECIST 1.1 criteria and pathological response at surgery, while safety will be monitored during treatment. The primary objective of this study is to explore whether switching to SHR-A1811 in combination with pertuzumab in patients with suboptimal early response can improve pathological complete response (pCR) rates. Secondary objectives include evaluation of safety and tolerability of the treatment strategies. This study aims to provide evidence for an individualized, response-adapted neoadjuvant treatment approach in HER2-positive breast cancer, and to optimize treatment outcomes for patients with inadequate response to standard therapy.

Conditions

Breast Cancer

Keywords

HER2-positive; Neoadjuvant therapy; Antibody-drug conjugate; SHR-A1811; HER2-targeted therapy

Outcome Measures

Primary Outcomes (1)

• Total Pathological Complete Response (tpCR)

  Number of participants achieving total pathological complete response, defined as no residual invasive cancer in both breast and axillary lymph nodes (ypT0/is ypN0) at the time of surgery following completion of neoadjuvant therapy.Metric：Proportion of participants (%)

  At surgery (approximately 18 weeks after initiation of treatment)

Secondary Outcomes (6)

• Objective Response Rate (ORR) per RECIST v1.1

  From baseline to surgery (approximately 18 weeks)

• Event-Free Survival (EFS)

  From first dose up to 3 years

• Breast Conservation Rate

  At surgery (approximately 18 weeks)

• Number of Participants With Treatment-Related Adverse Events (TRAEs)

  From first dose to 30 days after last dose

• Number of Participants With Grade ≥3 Adverse Events

  From first dose to 30 days after last dose

Other Outcomes (2)

• Change in Circulating Tumor DNA (ctDNA) Levels

  Baseline, after 2 cycles (~6 weeks), and pre-surgery (~18 weeks)

• Predictive Performance of Multi-modal Biomarker Model for Treatment Response

  Up to surgery (~18 weeks)

Study Arms (2)

Standard Neoadjuvant Therapy (THP/TCbHP)

ACTIVE COMPARATOR

All enrolled patients will initially receive 2 cycles of standard neoadjuvant therapy with trastuzumab, pertuzumab, and chemotherapy (THP or TCbHP). Patients who achieve a tumor reduction greater than 40% according to RECIST version 1.1 will continue the same regimen for an additional 4 cycles.

Drug: Pertuzumab; Drug: trastuzumab; Drug: Chemotherapy

SHR-A1811 Plus Pertuzumab

EXPERIMENTAL

All enrolled patients will initially receive 2 cycles of standard neoadjuvant therapy. Patients with a tumor reduction of 40% or less according to RECIST version 1.1 will switch to SHR-A1811 in combination with pertuzumab for 4 cycles.

Drug: SHR-A1811; Drug: Pertuzumab

Interventions

SHR-A1811 DRUG

SHR-A1811 is a HER2-targeted antibody-drug conjugate administered intravenously in combination with pertuzumab as neoadjuvant therapy.

SHR-A1811 Plus Pertuzumab

Pertuzumab DRUG

Pertuzumab is a monoclonal antibody targeting HER2, administered intravenously as part of dual HER2 blockade.

SHR-A1811 Plus Pertuzumab; Standard Neoadjuvant Therapy (THP/TCbHP)

trastuzumab DRUG

Trastuzumab is a HER2-targeted monoclonal antibody administered intravenously as part of standard neoadjuvant therapy.

Standard Neoadjuvant Therapy (THP/TCbHP)

Chemotherapy DRUG

Chemotherapy includes taxane-based regimens with or without carboplatin (THP or TCbHP) administered according to institutional standards.

Standard Neoadjuvant Therapy (THP/TCbHP)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet all of the following criteria:
• Age ≥18 and ≤70 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• At least one measurable lesion according to RECIST version 1.1.
• Histologically confirmed invasive breast cancer with clinical stage:
• Stage II (T2N0-1M0 or T3N0M0), or Stage III (T2N2-3M0, T3N1-3M0, or T4N0-3M0). 5.HER2-positive invasive breast cancer confirmed by histopathology, defined as: HER2 immunohistochemistry (IHC) 3+, or HER2 IHC 2+ with fluorescence in situ hybridization (FISH) positivity, as determined by the pathology department of the participating center. 6.Adequate organ function, defined as:
• Hematologic function (no blood transfusion, blood products, granulocyte colony-stimulating factor \[G-CSF\], or other hematopoietic growth factors within 14 days prior to testing):
• Hemoglobin (Hb) ≥100 g/L; Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L; Platelet count (PLT) ≥100 × 10⁹/L.
• Biochemical function:
• Total bilirubin (TBIL) ≤1 × upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1.5 × ULN; Alkaline phosphatase (ALP) ≤2.5 × ULN; Blood urea nitrogen (BUN) and serum creatinine (Cr) ≤1.5 × ULN.
• Cardiac function:
• Left ventricular ejection fraction (LVEF) ≥55% by echocardiography; QT interval corrected by Fridericia's formula (QTcF) ≤450 ms. 7.Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to enrollment and agree to use effective contraception during the study and for at least 8 weeks after the last dose of study treatment.
• Willingness to participate in the study, provide written informed consent, and comply with study procedures and follow-up.

You may not qualify if:

• Participants meeting any of the following criteria will be excluded:
• Prior receipt of any anti-tumor therapy not specified in the study protocol, including but not limited to chemotherapy, radiotherapy, targeted therapy, or endocrine therapy for the current breast cancer.
• Concurrent receipt of any other anti-tumor therapy during the study. Bilateral breast cancer, inflammatory breast cancer, or occult breast cancer. Stage IV (metastatic) breast cancer.
• History of other malignancies within the past 5 years, except for adequately treated carcinoma in situ of the cervix.
• Severe dysfunction of major organs, including but not limited to cardiac, hepatic, or renal insufficiency.
• Participation in another interventional clinical trial within 4 weeks prior to enrollment.
• Known hypersensitivity to any component of the study drugs; history of immunodeficiency, including positive human immunodeficiency virus (HIV) test, active hepatitis C virus (HCV) infection, active hepatitis B infection, congenital or acquired immunodeficiency disorders, or history of organ transplantation.
• History of significant cardiac disease, including but not limited to:
• Clinically significant arrhythmia requiring treatment; Myocardial infarction; Heart failure;
• Any other cardiac condition that, in the investigator's judgment, makes the participant unsuitable for the study.
• Pregnant or breastfeeding women; women of childbearing potential with a positive pregnancy test at baseline or unwilling to use effective contraception throughout the study period.
• Any serious concomitant disease that, in the investigator's judgment, may compromise patient safety or interfere with study participation, including but not limited to uncontrolled hypertension, severe diabetes, or active infection.
• History of neurological or psychiatric disorders, including epilepsy or dementia.
• Any other condition that, in the investigator's judgment, makes the participant unsuitable for participation in this study.

Sponsors & Collaborators

• Hebei Medical University Fourth Hospital: lead
• Jiangsu Hengrui Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

The Fourth Hospital of Hebei Medical University

Shijiazhuang, Hebei, 050000, China

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pertuzumab; Trastuzumab; Drug Therapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics

Central Study Contacts

Li Ma, MD

CONTACT

13932116886; mali1021@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician, Breast Center

Model Details: All enrolled patients will receive 2 initial cycles of standard neoadjuvant therapy with trastuzumab, pertuzumab, and chemotherapy (THP or TCbHP). Tumor response will then be assessed according to RECIST version 1.1 criteria. Based on early response evaluation, patients will be assigned to subsequent treatment strategies. Patients demonstrating a tumor reduction greater than 40% will continue the same neoadjuvant regimen for an additional 4 cycles. Patients with a tumor reduction of 40% or less will switch to an alternative treatment consisting of SHR-A1811 in combination with pertuzumab for 4 cycles. This response-adapted, sequential assignment design allows treatment modification according to early tumor response, with the aim of optimizing therapeutic outcomes.

Study Record Dates

• First Submitted: April 1, 2026
• First Posted: April 14, 2026
• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2029
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

CN (1)