study of shr-a1921 combined adebrelimab in hr-positive, her2-negative advanced breast cancer

Conditions: Advanced Breast Cancer; Hormone-receptor-positive Breast Cancer; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast

Summary: our study is aimed to evaluate the efficacy and safety of novel adc named shr-a1921 combined with adebrelimab in endocrine therapy-failed hr (hormone receptor)-positive, her2-negative advanced breast cancer.


Eligibility criteria:
inclusion criteria: * 18 years to 75 years old, female patients with breast cancer; * ecog ps score: 0\~1; * histologically or cytologically confirmed hr-positive, her2-negative advanced or metastatic breast cancer; * pd-l1 positive; * disease progression after at least prior 2 lines of endocrine therapy, and unable to benefit from further endocrine therapy determined by investigator, of which at least one line of cdk4/6 inhibitor-based treatment; if recurrence or metastasis within 2 years after completion of adjuvant endocrine therapy, marked as first-line treatment; * prior at least 1 line of systemic chemotherapy in recurrent or metastatic setting; * based on recist v1.1, at least one measurable lesion; * patients must have a life expectancy ≥ 3 months; * adequate organ function and marrow function (no corrective treatment within 14 days before first dose); * women of childbearing potential (wocbp) should agree to use an effective method of contraception and no lactation from the initiation of screening to 7 months after the last dose of study therapy; wocbp should have a negative serum pregnancy result within 7 days before the first dose of study therapy; * willing and able to provide written informed consent and comply with the requirements and restrictions in the protocol. exclusion criteria: * has leptomeningeal metastasis confirmed by mri or lumbar puncture; * has cns metastasis confirmed by radiology, except following conditions: ①asymptomatic brain metastasis that is not required to radiotherapy or surgery immediately; ②prior local therapy (e.g. radiotherapy or surgery) for brain or dural metastasis, of which stable disease lasting at least 4 weeks confirmed by radiography, and symptomatic therapy (e.g. hormone, mannitol, bevacizumab) has been stopped beyond 2 weeks with no clinical symptom; * prior anti-trop-2 treatment; * has received or been receiving pd-(l)1 inhibitors and/or adc containing a topoisomerase inhibitor-like payload; * existence of third space fluid (e.g. massive ascites, pleural effusion, pericardial effusion) that is not well controlled by effective methods, e.g. drainage; * 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; * use of other antitumor systemic treatment during the study; * has active autoimmune disease or a history of autoimmune disease; * known history of immunodeficiency, including hiv-positive, other acquired or innate immunodeficient disease, or known history of organ transplantation; * 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; * 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); * 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; * 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; * hypersensitivity to study therapy or any of its excipients; * has known clinically significant lung disease, including but not limited to: interstitial lung disease, pneumonitis, pulmonary fibrosis; * known history of uncontrolled cardiovascular clinical symptom or disease that is not well controlled; * 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; * other conditions that might influence the study and analysis of results in the opinion of the investigator.