Anlotinib With Trastuzumab Deruxtecan for Previously Treated HER2-Low Advanced Breast Cancer

Inclusion criteria

• 1. Age 18 - 75 years; ECOG PS 0 or 1. 2. Pathologically documented breast cancer that:

• Is unresectable or metastatic.
• Has a history of low HER2 expression (IHC 1+& IHC 2+/ISH- or 0<IHC<1+).
• Is HR-positive or HR-negative.
• Has progressed on, and would no longer benefit from, endocrine therapy.
• Has been treated with ≥1 prior lines of chemotherapy/adjuvant in the recurrent or metastatic setting.

• At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1（Previously treated lesions with radiotherapy or focal therapy and no progression cannot be included as target lesion for assessment）.

• Has protocol-defined adequate bone marrow, renal, hepatic and blood clotting functions.

• Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and after the last dose for at least 6 months.

Exclusion criteria

• Has previously been treated with anti-angiogenic targeted small molecule therapy.
• Prior treatment with antibody drug conjugate with a topoisomerase I inhibitor exatecan derivative.
• Has a history of (noninfectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• Has unresolved toxicities from previous anticancer therapy.
• Has uncontrolled or significant cardiovascular disease.
• Has any bleeding event, unhealed wounds, ulcerative or fractures.
• Has arterial or venous thromboembolic events occurred within 6 months.
• Has spinal cord compression or clinically active central nervous system metastases.
• Has any other condition that per protocol or in the opinion of the investigator is inappropriate for the study.