Trastuzumab Rezetecan vs Trastuzumab Deruxtecan in the Neoadjuvant Treatment of HER2 Positive Breast Cancer

A Randomized, Open-Label, Phase II Study Comparing the Efficacy and Safety of Trastuzumab-rezetecan and Trastuzumab Deruxtecan (T-DXd) in Neoadjuvant Treatment of Patients With HER2-Positive Early or Locally Advanced Breast Cancer

This is a single-center, randomized, open-label, phase II interventional study. Eligible patients will be randomized 1:1 to receive either Trastuzumab-rezetecan (4.8 mg/kg Q3W) or T-DXd (5.4 mg/kg Q3W) for 8 neoadjuvant cycles. After completing neoadjuvant treatment, patients will undergo definitive surgery, and tpCR will be assessed from resected specimens. Patients will then be followed up to monitor long-term efficacy (e.g., EFS) and late-onset adverse events. A total of 68 patients (34 per arm) will be enrolled to achieve the study's statistical objectives.

Inclusion Criteria:

1. Female, 18-75 years old, treatment-naive
2. ECOG PS 0-1
3. Histologically confirmed HER2+ (IHC 3+ or IHC 2+/ISH+) early/locally advanced breast cancer (AJCC 8th: cT2-cT4 any N cM0) or cT1c N+ cM0; known ER/PR status
4. Adequate organ function (hematology/biochemistry/coagulation/urine/cardiac)
5. Negative pregnancy test (childbearing women); agree to effective contraception
6. Sign an informed consent form.

Exclusion Criteria:

1. Bbilateral/inflammatory/occult breast cancer.
2. Prior anti-tumor therapy (chemotherapy/radiotherapy/targeted therapy, etc.); radical radiotherapy (4 weeks prior) or palliative radiotherapy (2 weeks prior) to first dose.
3. Concurrent anti-tumor therapy; other malignancies (within past 5 years, except cured basal cell carcinoma/cervical CIS).
4. Prior trial participation (past 4 weeks); systemic immunosuppressants/hormones (>10 mg/day prednisone equivalent, 2 weeks prior; nasal/inhaled steroids excluded).
5. Live/attenuated vaccine (past 4 weeks); major non-breast surgery (4 weeks prior, incomplete recovery).
6. Active/relapsing autoimmune disease (except controlled hypothyroidism/well-managed skin diseases/type 1 diabetes); immunodeficiency (HIV+/organ transplant).
7. Uncontrolled cardiovascular/cerebrovascular disease (e.g., MI/stroke in 6 months, NYHA III-IV heart failure, QTcF >470 msec [female]).
8. Active ILD/severe lung disease; active hepatitis B (HBsAg+ & HBV DNA ≥500 IU/mL)/hepatitis C (HCV RNA+); severe infection requiring anti-infective therapy.
9. Bleeding/thrombotic tendency; hypersensitivity to study drugs/excipients.
10. Pregnant/lactating women; women of childbearing potential with positive pregnancy test or refusing contraception.
11. Other conditions (e.g., uncontrolled hypertension/diabetes, neuropsychiatric disorders) deemed unsuitable by the investigator.