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
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Shanghai Jiao Tong University School of Medicine
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- pCR
Overview
Brief Summary
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 Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
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.
- •ECOG Performance Status: ECOG functional status score of 0\~
- •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%.
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.
Arms & Interventions
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.
Intervention: Trastuzumab Deruxtecan (Drug)
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.
Intervention: Pertuzumab (Drug)
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.
Intervention: Taxane Chemotherapy (Drug)
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.
Intervention: Trastuzumab (or biosimilar) (Drug)
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.
Intervention: Pyrotinib 320mg (Drug)
Outcomes
Primary Outcomes
pCR
Time Frame: after neoadjuvant treatment, at surgery
ypT0/Tis ypN0
Secondary Outcomes
- ORR(after neoadjuvant treatment, at surgery)
- EFS(From enrollment to 5 years after surgery)
- OS(From enrollment to 5 years after surgery)
- bpCR(after neoadjuvant treatment, at surgery)
Investigators
Kunwei Shen
Head of Comprehensive Breast Health Center
Ruijin Hospital