Adebrelimab Combined With Dalpiciclib and Standard Endocrine Therapy for HR+/HER2 - Advanced Breast Cancer

Study Overview
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Brief Summary
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This is a prospective, single-arm, multicenter Phase II study of patients with advanced HR+/HER2- breast cancer who are untreated or have failed previous first-line endocrine therapy。The primary objective of this study was to explore the efficacy and safety of the PD-L1 inhibitor adebrelimab in combination with the CDK4/6 inhibitor Dalpiciclib and standard endocrine therapy in advanced HR+/ HER2-breast cancer.

Official Title
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Adebrelimab Combined With Dalpiciclib and Standard Endocrine Therapy for HR+/HER2 - Advanced Breast Cancer:a Single-arm, Phase II Exploratory Clinical Study

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Adebrelimab
* Drug: dalpiciclib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Premenopausal/perimenopausal or postmenopausal women aged ≥18 years and ≤75 years; Histologically confirmed HR+/HER2- invasive breast cancer (specific definition: ER >10% tumor cell positive is defined as ER positive, PR >10% tumor cell positive is defined as PR positive, ER and/or PR positive is defined as HR positive; HER2 0-1+ or HER2 ++ but negative by FISH test, no amplification, defined as HER2 negative); Locally advanced breast cancer (radical local treatment is not possible) or recurrent metastatic breast cancer; Did not receive any systemic anti-cancer therapy at the stage of recurrence and metastasis or failed to receive first-line endocrine therapy at the advanced stage; Have at least one measurable lesion according to RECIST version 1.1 Adequate hematology and organ function, including: hemoglobin > 9 g/dL without blood transfusion or erythropoietin in the past 14 days. ANC ≥ 1.5×109/L without using granulocyte colony stimulating factor in the past 14 days. PLT ≥ 75×109/L without blood transfusion in the past 14 days. TBIL ≤ 1.5 ×ULN (Gilbert syndrome allows ≤ 3 × ULN). ALT and AST ≤ 3 × ULN (if there is liver metastasis, ALT and AST ≤ 5 × ULN). Serum Cr ≤ 1.5 × ULN or endogenous creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula) ECOG score 0 or 1, and life expectancy ≥3 months; Fertile female subjects are required to use a medically approved contraceptive during the study treatment period and for at least 3 months after the last use of the study drug; Subjects voluntarily joined the study, signed informed consent, had good compliance, and cooperated with follow-up. Exclusion Criteria: Previous use of CDK4/6 inhibitors or PD1/PD-L1 monoclonal antibody Uncontrolled central nervous system metastasis (meaning symptoms or the use of glucocorticoids or mannitol to control symptoms); A history of clinically significant or uncontrolled heart disease, including congestive heart failure, angina pectoris, myocardial infarction within the last 6 months, or ventricular arrhythmia; Radiotherapy, chemotherapy, surgery, or other targeted and immunotherapy for advanced HR+/HER2- breast cancer within 4 weeks prior to first administration of the study drug; Pregnant or lactating patients; Malignant tumors within the past three years (except for cured basal cell carcinoma of the skin and cervical carcinoma in situ); Significant comorbidities, including mental illnesses that the investigator believes will adversely affect the patient's participation in the study; Those who have received anti-tumor vaccine or have received live vaccine within 4 weeks before the first administration of the investigational drug; Patients with known HBV or HCV infection active phase or HBV DNA≥500, or chronic phase with abnormal liver function; History of active autoimmune disease (such as interstitial pneumonia, colitis, hepatitis, pituitaritis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes) A history of immunodeficiency, including HIV testing positive, or other acquired, congenital immunodeficiency diseases, or a history of organ transplantation and allogeneic bone marrow transplantation; History of interstitial lung disease (except radiation pneumonia without hormone therapy) and non-infectious pneumonia; Patients with active infection or who had been treated with systemic immune stimulating factors within 4 weeks prior to enrollment; Allergic physique, or known allergic history of the drug components of this program; Or allergic to other monoclonal antibodies; Previous thyroid dysfunction; The investigator did not consider the patient suitable for participation in any other conditions of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment group<br>Adebrelimab: 1200mg intravenously ,Q3W dalpiciclib : 150mg once a day for 3 weeks, stop for 1 week, Q4W Endocrine recommended drugs untreated: aromatase inhibitors (letrozole/anastrozole/exemestane), given orally once daily at a specific dose (letrozole 2.5mg/ day; Anastrozole 1mg/ day, exemestane 25mg/ day); first-line endocrine therapy failed: fluvestrant was given once every 28 days, 500mg intramuscular injection, and then 500mg intramuscular injection 2 weeks after the first administration; | Drug: Adebrelimab<br>* adebrelimab:1200mg intravenously, Q3W.<br>* Other names: SHR-1316;Drug: dalpiciclib<br>* dalpiciclib:150mg once a day for 3 weeks and stop for 1 week. Q4W.<br>* Other names: SHR-6390;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival(PFS) | PFS is defined as the time from enrollment to the first imaging disease progression or death (whichever occurs first). Assessed according to RECIST v1.1 by investigator. | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | ORR is defined as the proportion of patients with complete response(CR) and partial response(PR) assessed by the investigator in accordance with the RECIST 1.1 criteria. | Up to 3 years | 
| Overall survival (OS) | OS is defined as the time between enrollment and the patient's death due to any OS is defined as the time between enrollment and the patient's death due to any cause | Up to 5 years | 
| Safety and Tolerability | Safety includes the adverse event profile of sintilimab and bevacizumab according to the Common Terminology Criteria for Adverse Events version 5.0. | Up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HR+/HER2- breast cancer, adebrelimab, dalpiciclib