Pre-surgery trastuzumab deruxtecan (SHR-A1811) plus pertuzumab for HER2-positive 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

This trial tests giving trastuzumab deruxtecan (SHR-A1811) with pertuzumab before surgery to see if it helps women with stage II–III HER2-positive breast cancer achieve a complete response.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years to 70 Years
• Sex: Female
• Sponsor: Shanghai Jiao Tong University School of Medicine (Academic / other)
• Drugs / interventions: chemotherapy, Trastuzumab, Pertuzumab, Pyrotinib
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07393425 on ClinicalTrials.gov

What this trial studies

This is a phase 2, single-center interventional trial treating women with stage II–III HER2-positive invasive breast cancer with three cycles of trastuzumab deruxtecan (SHR-A1811) plus pertuzumab followed by imaging. Patients who achieve clinical or radiologic complete (or near-complete) response receive three additional cycles of the same regimen prior to surgery. Patients without adequate response are switched to a paclitaxel-based regimen combined with trastuzumab and oral pyrotinib for three cycles before surgery. Eligibility requires age 18–70, ECOG 0–1, measurable disease per RECIST v1.1, adequate organ function, and HER2 positivity by IHC 3+ or IHC 2+ with ISH amplification.

Who should consider this trial

Good fit: Women aged 18–70 with histologically confirmed stage II–III HER2-positive invasive breast cancer, ECOG 0–1, measurable disease, adequate organ function, and no prior systemic therapy are the intended participants.

Not a fit: Patients with metastatic (M1) disease, HER2-negative tumors, prior systemic breast cancer therapy, poor organ function, ECOG >1, or those outside the age range are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could shrink tumors before surgery so more patients have little or no visible cancer at the time of operation and may avoid more extensive surgery.

How similar studies have performed: Trastuzumab deruxtecan has shown strong efficacy in metastatic HER2-positive disease and emerging neoadjuvant data suggest high response rates, but combining it with pertuzumab in the preoperative setting is relatively new.

Eligibility criteria

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.

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai Jiaotong University School of Medicine affiliated Ruijin Hospital — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Xiaosong Chen, Ph.D

Conditions HER2 + Breast Cancer; Trastuzumab Deruxtecan; SHR-A1811; neoadjuvant