Neoadjuvant Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab in HER2+ Breast Cancer

Neoadjuvant Therapy With Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab or Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab Sequenced With Paclitaxel-based Regimens + Trastuzumab + Pyrotinib in HER2+ Breast Cancer

Patients with Stage II-III HER2-positive breast cancer will receive three cycles of treatment with Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab, followed by imaging assessment. If clinical complete response (cCR) or radiological complete response/near radiological complete response (rCR/near rCR) is achieved, they will continue to receive an additional three cycles of treatment with Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab, followed by surgery.

If cCR/rCR or near rCR is not achieved, the treatment will be switched to the THPy regimen (paclitaxel-based regimen + Trastuzumab + Pyrotinib) for three cycles.

Study Overview

• Status: Recruiting
• Conditions: HER2 + Breast Cancer
• Intervention / Treatment: Drug: Trastuzumab Deruxtecan; Drug: Pertuzumab; Drug: Taxane Chemotherapy; Drug: Trastuzumab (or biosimilar); Drug: Pyrotinib 320mg

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaosong Chen, Ph.D; Phone Number: +86-21-64370045-602102; Email: chenxiaosong0156@hotmail.com
• Study Contact Backup: Name: Jiayi Wu, Ph.D; Phone Number: +86-21-64370045-602101; Email: pinkscorpio@163.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Recruiting
      • Shanghai Jiaotong University School of Medicine affiliated Ruijin Hospital
      • Contact: Xiaosong Chen; Phone Number: +86-21-64370045-602102; Email: xiaosongchen0156@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age and Gender: Female patients aged ≥18 years and ≤70 years. Histological Confirmation: Patients must have histologically confirmed invasive breast cancer and must not have received any prior systemic anti-tumor therapy for breast cancer.
• HER2 Positivity: Histologically confirmed HER2 receptor positivity, following the 2018 ASCO-CAP HER2 positivity judgment guidelines.

Confirmed by pathology laboratory with immunohistochemistry (IHC) score of 3+, or 2+ with positive in situ hybridization (ISH) test (ISH amplification rate ≥2.0).

• Tumor Stage: Patients must have tumor staging conforming to the Stage II-III breast cancer criteria according to the eighth edition of the AJCC breast cancer TNM staging system (T1~T4, N1~N3, M0).
• Measurable Target Lesion: At least one measurable target lesion according to RECIST V1.1.
• ECOG Performance Status: ECOG functional status score of 0~1.

• Organ Function: Adequate organ function levels, with the following requirements (no blood transfusion or use of leukocyte or platelet elevation drugs within 2 weeks prior to screening):

  • Hematology: Absolute neutrophil count (ANC) > 1.5 × 109/L; Platelet count (PLT) > 75 × 109/L; Hemoglobin (Hb) > 90 g/L.
  • Blood Chemistry: Total bilirubin (TBIL) < 1.5 × ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 1.5 × ULN; Alkaline phosphatase < 2.5 × ULN; Blood urea nitrogen/urea (BUN/UREA) and creatinine (Cr) < 1.5 × ULN.
  • Cardiac Ultrasound: Left ventricular ejection fraction (LVEF) ≥ 55%.
  • 12-Lead ECG: Fridericia's method corrected QT interval (QTcF) < 470 msec.
• Reproductive Status: For premenopausal women with potential fertility, a pregnancy test must be performed within 7 days before treatment initiation, with negative serum/urine pregnancy results.
• Patients must not be lactating and must use adequate barrier contraception throughout the treatment cycle and for 6 months after treatment completion.

Voluntary Participation: Voluntary participation in the study with signed informed consent, good compliance, and willingness to cooperate with visit schedules and research-related procedures.

Exclusion Criteria:

• Stage IV Breast Cancer: Patients with Stage IV breast cancer. Inflammatory Breast Cancer: Patients with inflammatory breast cancer. Prior Malignancy Treatment: Patients who have received prior anti-tumor therapy or radiotherapy for any malignancy, or have concurrent other malignancies, excluding cured cervical intraepithelial neoplasia, basal cell carcinoma, or squamous cell carcinoma.
• Concurrent Anti-Tumor Therapy: Patients currently participating in other clinical trials involving anti-tumor therapy, including but not limited to chemotherapy, endocrine therapy, biological therapy, bone modification therapy, or immune checkpoint inhibitor therapy.
• Recent Surgery: Patients who have undergone major surgery unrelated to breast cancer within 4 weeks prior to the first dose of the study drug, or have not fully recovered from such surgery.
• Serious Cardiac Disease: Patients with serious cardiac conditions, including but not limited to:
• History of heart failure or systolic dysfunction (LVEF < 50%). Uncontrolled high-risk arrhythmia, such as atrial tachycardia, resting heart rate > 100 bpm, significant ventricular arrhythmia, or advanced atrioventricular block (i.e., Mobitz II second-degree or third-degree atrioventricular block).
• Angina pectoris requiring medication.
• Clinically significant heart valve disease.
• ECG showing transmural myocardial infarction.
• Uncontrolled hypertension (after medication, systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg).
• Uncontrolled Active Infection: Patients with uncontrolled active infection requiring treatment, or with a history of immunodeficiency, including HIV positivity, other acquired or congenital immunodeficiency diseases, or a history of organ transplantation.
• Allergy to Study Drugs: Patients with a known history of allergy to any component of the study drugs.
• Pregnant or Lactating Women: Pregnant or lactating women, women of childbearing potential with positive baseline pregnancy test, or those unwilling to use effective contraception during the trial period and for 6 months after the last dose of the study drug.
• Interstitial Lung Disease: Patients with known or suspected interstitial lung disease; those with other severe pulmonary diseases that may interfere with drug-related pulmonary toxicity detection or management within 3 months prior to the first dose, including but not limited to idiopathic pulmonary fibrosis, organizing pneumonia/obliterative bronchiolitis, pulmonary embolism, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive/obstructive lung disease, or any pulmonary autoimmune or inflammatory disease such as rheumatoid arthritis, Sjögren's syndrome, or sarcoidosis; or those with a history of total pneumonectomy.
• Severe Concomitant Diseases: Patients with severe concomitant diseases or other conditions that may interfere with the planned treatment, or those deemed unsuitable for the study by the investigator for any other reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Study Arm; Patients will receive three cycles of treatment with Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab, followed by imaging assessment. If clinical complete response (cCR) or radiological complete response/near radiological complete response (rCR/near rCR) is achieved, they will continue to receive an additional three cycles of treatment with Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab, followed by surgery.Patients who did not achieve cCR/rCR or near rCR at the end of cycle 3 will change to the THPy regimen (paclitaxel-based regimen + Trastuzumab + Pyrotinib) for three cycles.

Drug: Trastuzumab Deruxtecan; 4.8mg/kg, d1, q3w; Other Names: A1811; Drug: Pertuzumab; 840mg on cycle1, 420mg on following cycles, d1, q3w; Drug: Taxane Chemotherapy; Nab-paclitaxel 100 mg per square meter, d1,d8,d15 q3w Or Paclitaxel 80mg per square meter, d1,d8,d15 q3w Or Docetaxel 100mg per square meter, d1 q3w; Drug: Trastuzumab (or biosimilar); Trastuzumab 8mg/kg (loading dose) or 6mg/kg on following cycles, d1, q3w; Drug: Pyrotinib 320mg; 320mg qd

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR	ypT0/Tis ypN0	after neoadjuvant treatment, at surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	ORR per RECIST v1.1	after neoadjuvant treatment, at surgery
EFS	Event free survival	From enrollment to 5 years after surgery
OS	Overall survival	From enrollment to 5 years after surgery
bpCR	ypT0/is	after neoadjuvant treatment, at surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse events per NCI CTCAE 5.0	Safety per NCI CTCAE 5.0	From the day of first dose of study drug to 28 days after last dose of study drug, an average of 5 months

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University School of Medicine
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): February 2, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2032

Study Registration Dates

• First Submitted: February 1, 2026
• First Submitted That Met QC Criteria: February 5, 2026
• First Posted (Actual): February 6, 2026

Study Record Updates

• Last Update Posted (Actual): February 6, 2026
• Last Update Submitted That Met QC Criteria: February 5, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: neoadjuvant; Trastuzumab Deruxtecan; SHR-A1811
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Trastuzumab; pertuzumab; Biosimilar Pharmaceuticals; trastuzumab deruxtecan; pyrotinib
• Other Study ID Numbers: RJBC2502

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No