Study of ADCs Combined With Adebrelimab in HER2-negative Advanced Breast Cancer

A Phase II Study of Antibody-Drug Conjugates (ADCs) Combined With Adebrelimab in HER2-negative Advanced Breast Cancer

Our study is aimed to evaluate the efficacy and safety of novel ADCs named SHR-A1811, SHR-A1921 and SHR-A2102 combined with adebrelimab in HER2-negative advanced breast cancer.

Inclusion Criteria:

1. 18 years to 75 years old (including boundary values);
2. ECOG PS Score: 0~1;
3. Histologically or cytologically confirmed HER2-negative advanced breast cancer;
4. Disease progression after prior ≥1 line of systemic therapy; if HR-positive, prior CDK4/6 inhibitor is necessary;
5. Based on RECIST v1.1, at least one measurable lesion;
6. Brain metastasis with no clinical symptoms, or treated, stable brain metastases are eligible;
7. Patients must have a life expectancy ≥ 6 months;
8. Adequate organ function and marrow function (no corrective treatment within 14 days before first dose);
9. Women of childbearing potential should have a negative urine or serum pregnancy, and must promise to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study therapy or be celibate; Men who are not surgically sterile (including those sterilized by methods other than bilateral orchiectomy [e.g., vasectomy]) and who intend to have sexual intercourse with female partners of childbearing potential must use a contraceptive method from enrollment, throughout the study, and for 6 months after the end of the study to prevent partner pregnancy;
10. Available blood samples for ctDNA detection in the exploratory study;
11. Willing and able to provide written informed consent and comply with the requirements and restrictions in the protocol.

Exclusion Criteria:

1. Has known active brain metastasis which needs local therapy immediately;
2. Prior use of ADCs with the same target as study drugs;
3. Existence of third space fluid that is not well controlled by effective methods, e.g. drainage;
4. Has received antitumor surgery, radiotherapy, chemotherapy, targeted therapy or immunological therapy within 4 weeks before first dose of study therapy; has received antitumor endocrine therapy within one week before first dose of study therapy;
5. Use of other antitumor systemic treatment during the study;
6. Has active autoimmune disease or a history of autoimmune disease;
7. Known history of immunodeficiency, including HIV-positive, other acquired or innate immunodeficient disease, or known history of organ transplantation;
8. Has active hepatitis B (HBsAg-positive and HBV DNA≥500 IU/mL), hepatitis C (positive for HCV antibody and HCV RNA above ULN) and hepatic cirrhosis;
9. Has an active infection requiring antibiotics, antiviral or antifungal treatment, or pyrexia >38.5℃ of unknown origin during the screening period before first dose of study therapy (patients with pyrexia due to cancer could be enrolled determined by investigator);
10. Receiving immunosuppressive medication, or systemic corticosteroid therapy for the purpose of immunosuppression (prednisone at >10mg/d or equivalent dose of other corticosteroids), and continuous use within 2 weeks before the first dose of study therapy;
11. Other malignancy within prior 5 years unless curatively treated with no evidence of disease for at least recent 3 years, except: curatively treated in situ cancer of the cervix, skin basal cell carcinoma or skin squamous cell carcinoma;
12. Hypersensitivity to study therapy or any of its excipients;
13. Has known clinically significant lung disease, including but not limited to: interstitial lung disease, pneumonitis, pulmonary fibrosis;
14. Known history of uncontrolled cardiovascular clinical symptom or disease that is not well controlled;
15. Has received a live vaccine within 4 weeks before first dose of study therapy, or potential to receive a live vaccine during the trial treatment;
16. Women with a positive serum or urine pregnancy test or who are breastfeeding; patients of childbearing potential who are unwilling or not available to use an effective method of contraception;
17. Other conditions that might influence the study and analysis of results in the opinion of the investigator.