SHR-A1811 for HER2-positive Breast Cancer With Suboptimal Neoadjuvant Response

An Open-label, Single-arm, Multicenter Study of SHR-A1811 as Neoadjuvant Therapy in HER2-positive Breast Cancer Patients With Suboptimal Neoadjuvant Response

This is an open-label, single-arm, multicenter clinical study to evaluate the efficacy and safety of SHR-A1811 in early or locally advanced HER2-positive breast cancer patients with suboptimal response to neoadjuvant regimen. Patients who were determined by the researchers to have poor therapeutic effect will switch to SHR-A1811.

Patients will receive SHR-A1811, until completion or treatment discontinuation due to progression, toxicity, or withdrawal. The primary endpoint is tpCR (ypT0/is ypN0). Secondary endpoints include bpCR, RCB, EFS, and safety. The study will recruit 30 eligible patients from multiple centers in China.

Inclusion Criteria:

• 1.Female patients with newly diagnosed breast cancer aged 18 to 70 years old;
• 2.Early or locally advanced HER2-positive invasive breast cancer;
• 3.Known hormone receptor status;
• 4.ECOG score of 0-1;
• 5.Patients who were determined by the researchers to have poor therapeutic effect after 4 cycles of neoadjuvant therapy;
• 6.Organ function levels must meet the following requirements:
• 7.Women of childbearing age must undergo a serum pregnancy test within 7 days before enrollment, with a negative result, and be willing to use a medically approved highly effective contraceptive method during the study and within 3 months after the last administration of the study drug.
• 8.The subjects voluntarily participate in this study and sign the informed consent form.

Exclusion Criteria:

• 1. Patients with metastatic or bilateral breast cancer, or inflammatory breast cancer
• 2. Patients with grade 3 or higher thrombocytopenia during previous treatment, or grade 3 or higher nausea and vomiting despite primary prevention
• 3. History of other malignant tumors (except cured carcinoma in situ of the cervix, basal cell carcinoma, etc.) and related treatment history
• 4. Patients who received major non-breast cancer surgery within 4 weeks before enrollment and have not recovered (except biopsy and PICC)
• 5. Autoimmune diseases (except special cases such as hypothyroidism and stable type 1 diabetes)
• 6. Interstitial lung disease, non-infectious pneumonia, uncontrolled systemic diseases
• 7. History of or planned administration of live attenuated vaccines within 28 days
• 8. HIV infection, active hepatitis (hepatitis B, hepatitis C, etc.), autoimmune hepatitis
• 9. Severe infection within 4 weeks, CTCAE grade ≥ 2 active infection within 2 weeks (except neoplastic fever), or evidence of active tuberculosis within 1 year
• 10. History of allogeneic bone marrow or solid organ transplantation
• 11. Peripheral neuropathy of grade ≥ 2
• 12. Severe heart diseases
• 13. Receipt of systemic immunostimulant therapy within 4 weeks
• 14. Receipt of systemic immunosuppressant therapy within 2 weeks (except local or physiological dose of hormones)
• 15. Allergy to study drugs/excipients, or history of severe allergic reaction to other monoclonal antibodies
• 16. Pregnant or lactating women; fertile women with positive pregnancy test or unwilling to take effective contraception throughout the trial
• 17. History of neurological/psychiatric disorders , or history of substance abuse, alcoholism, or drug addiction
• 18. Other circumstances deemed unsuitable for enrollment by the researcher