A Trial of Trastuzumab Rezetecan in Unresectable Locally Recurrent/Metastatic Breast Cancer

A Randomized, Open-Label, Multicenter Phase II Clinical Study of Different Doses of Trastuzumab Rezetecan for Injection or Trastuzumab Deruxtecan for Injection in the Treatment of Unresectable Locally Recurrent/Metastatic Breast Cancer With HR-Positive and HER2-Low Expression

The study is designed to compare the efficacy and safety of different dose groups of Trastuzumab Rezetecan or Trastuzumab Deruxtecan in patients with HR-positive, HER2-low unresectable locally recurrent/metastatic breast cancer. It will also exploratively evaluate the pharmacokinetic profile and immunogenicity of Trastuzumab Rezetecan.

Inclusion Criteria:

1. Female aged 18 to 75 years (inclusive).
2. Unresectable locally recurrent or metastatic breast cancer.
3. Prior therapy must meet the following: No prior chemotherapy for recurrent/metastatic disease. Must have received at least one prior line of endocrine therapy for recurrent/metastatic disease with disease progression, and the investigator judges that further benefit from endocrine therapy is not possible.
4. Documented radiological disease progression (during or after the most recent therapy).
5. ECOG performance status of 0 or 1.
6. Life expectancy ≥ 12 weeks.
7. At least one extracranial measurable lesion as a target lesion according to RECIST v1.1 criteria.
8. Adequate function of major organs.
9. Pregnancy and contraception: Women of childbearing potential (WOCBP) must agree to use highly effective contraception from study screening until 7 months after the last dose of study drug and agree not to breastfeed; serum pregnancy test result must be negative within 7 days before the first dose.
10. The patient voluntarily participates in this study, signs the informed consent form, has good compliance, and is willing to cooperate with visits and study-related procedures.

Exclusion Criteria:

1. Presence of leptomeningeal metastasis/carcinomatous meningitis, spinal cord compression, or active central nervous system metastases.
2. Patients with only skin or brain lesions as target lesions.
3. History of other malignancies within the past 5 years, except for cured basal cell carcinoma of the skin or carcinoma in situ of the cervix.
4. Presence of carcinomatous lymphangitis, or third-space fluid accumulation that cannot be controlled by methods such as drainage.
5. Prior surgery, chemotherapy, immunotherapy, or macromolecular targeted therapy within 4 weeks before the first dose; prior endocrine therapy, chemotherapy with 5-FU analogs, or radiotherapy within 2 weeks before the first dose; small molecule targeted agents require a washout period of 2 weeks or 5 half-lives; other investigational drugs require a washout period of 4 weeks or 5 half-lives before the first dose.
6. Use of immunosuppressants or systemic corticosteroids for immunosuppressive purposes within 2 weeks before the first dose for therapeutic intent.
7. History of immunodeficiency, including a positive HIV test, other acquired or congenital immunodeficiency diseases, or history of organ transplantation.
8. Clinically significant cardiovascular disease, such as severe/unstable angina, symptomatic congestive heart failure, etc.; clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention; myocardial infarction or cerebrovascular accident within 6 months before the first dose.
9. Participants with known or suspected interstitial lung disease; other moderate-to-severe pulmonary diseases that may interfere with the detection or management of drug-related pulmonary toxicity and severely affect respiratory function within 3 months before the first dose; and any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement.
10. Known hereditary or acquired bleeding tendency.
11. Active hepatitis B, hepatitis C, or cirrhosis; or severe infection requiring control with antibiotics, antivirals, or antifungals.
12. Toxicities from prior anti-tumor therapy have not recovered to ≤ Grade 1 (according to NCI-CTCAE v5.0).
13. Any other severe physical or mental illness or laboratory abnormality that may increase the risk associated with study participation, interfere with study results, or any other condition for which the investigator considers the patient unsuitable for participation in this study.