Breast Cancer, HR+/HER2- Breast Cancer
Conditions
Brief summary
This study intends to explore the efficacy and safety of PD-L1 inhibitor Adebrelimab combined with the CDK4/6 inhibitor Dalpcicilib and standard endocrine therapy given as neoadjuvant treatment in stages II-III hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer.
Detailed description
This single-center, open-label, single-arm clinical trial aims to evaluate the efficacy and safety of the neoadjuvant treatment with the PD-L1 inhibitor Adebrelimab in combination with the CDK4/6 inhibitor Dalpicicilib in combination with standard endocrine therapy, for stages II-III hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer.
Interventions
DRUGAdebrelimab+Dalpciclib+Standard Endocrine Therapy
Adebrelimab: 1200mg, intravenously, Q4w Dalpiciclib: 150mg once a day for 3 weeks, stop for 1 week, Q4w Standard Endocrine Therapy: Choice of endocrine therapy is according to guidelines and centre policy by investigator
Sponsors
Harbin Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Postmenopausal women, aged ≥18 years; 2. Postmenopausal patients and all patients in the screening period must one of the following: * Previous bilateral oophorectomy, or aged ≥60 years; * Aged \<60 years, natural Postmenopausal status (defined as spontaneous cessation for at least 12 consecutive months without other pathological or physiological causes), E2 and FSH at the postmenopausal level; 3. 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); 4. Histologically confirmed invasive breast cancer, stage II-III breast cancer diagnosed based on AJCC cancer staging system (8th edition) ; 5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1; 6. According to the RECIST 1.1 standard, at least one measurable lesion exists; 7. The main organs have basically normal functions and meet the following conditions: * Bone marrow function: Hb≥90 g/L (no blood was transfused within 14 days); ANC≥1.5×109/L;PLT≥80×I09/L; * Liver and kidney function: TBlL≤1.5×ULN; ALT and AST≤3×ULN; serum Cr≤1.5 ULN and creatinine clearance\>50 ml/min (Cockcroft-Gault formula); 8. Subjects voluntarily joined the study, signed informed consent, had good compliance, and cooperated with follow-up.
Exclusion criteria
1. Previous use of CDK4/6 inhibitors or PD1/PD-L1 monoclonal antibody or concurrent treatment with any other antitumor therapy; 2. Severe organ dysfunction; 3. Inability to swallow,chronic diarrhea and intestinal obstruction,there are multiple factors that affect drug intake and absorption; 4. Patients with known HBV or HCV infection active phase or HBV DNA≥500, or chronic phase with abnormal liver function; 5. 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) 6. 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; 7. History of any heart disease, including:1)medicated or clinically significant arrhythmia; 2) myocardial infarction; 3) heart failure; 4) any other cardiac disease judged by the investigator for the trial; 8. Patients during pregnancy and lactation, women of childbearing age who refuse to take effective contraceptive measures during the study period; 9. According to the discretion of the investigator, there are significant risks to patient safety or concomitant diseases affecting the patient's completion of the study (including but not limited to severe hypertension, severe diabetes, active infection); 10. Have a clear history of neurological or psychiatric disorders, including epilepsy or dementia; 11. Any condition deemed inappropriate for the patient's participation in this study by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| tpCR rate | through study completion, an average of one and a half years | Total pathologic complete response (tpCR) rate, defined as ypT0/is, ypN0 as assessed by investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| OS | up to 3 years | OS is defined as the time between enrollment and the patient's death due to any cause. |
| EFS | up to 3 years | Event-Free Survival (EFS) is defined as the time from firest dose to disease progression, disease recurrence, or death, whichever comes first. |
| Ki67 | Baseline and At Surgery | Evaluation by a pathologist by manual counting according to WHO 2017 recommendations |
| ORR | Baseline up to Cycle 5（each cycle is 28 days） | Objective response rate(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. |
Countries
China
Outcome results
None listed