Immune Therapy in HR-positive/HER2-negative Metastatic Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 338
- 试验地点
- 1
- 主要终点
- PFS
研究概览
简要总结
This study is a prospective, open-label, phase II clinical study for patients with HR+/HER2- advanced breast cancer.
详细描述
Patients with SNF2 subtype of HR+/HER2- advanced breast cancer confirmed by the Department of Pathology and Key Laboratory of Breast Cancer of Fudan University Affiliated Cancer Hospital are planned to be enrolled. Five treatment arms were set up based on the whether they have exposed to CDK4/6 inhibitors before. The main purpose is to evaluate immune therapy in SNF2 subtype of HR+/HER2- advanced breast cancer and prepare for subsequent randomized controlled phase III clinical studies with larger sample size.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Females ≥18 years and ≤ 75 years old;
- •Histologically confirmed HR + / HER2- invasive breast cancer (specific definition: immunohistochemical detection of 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 is ++ but negative followed by FISH detection, no amplification, defined as HER2 negative);
- •Subtype of similarity network fusion-2 (SNF-2) confirmed by the Department of Pathology and Key Laboratory of Breast Cancer of Fudan University Affiliated Cancer Hospital
- •Locally advanced breast cancer (incapable of radical local treatment) or recurrent metastatic breast cancer;
- •Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1); or unmeasurable lytic or mixed (osteolytic + osteoblastic) bone lesions in the absence of measurable lesions;
- •Has adequate bone marrow function: absolute neutrophil count > 1.5x10ˆ9 /L; platelet count > 75x10ˆ9 /L, hemoglobin > 9g/dL;
- •Patients had received no previous chemotherapy or targeted therapy for metastatic disease
- •Has adequate liver function and kidney function: serum creatinine
- •ECOG score ≤ 2 and life expectancy ≥ 3 months;
- •Participants voluntarily joined the study, has signed informed consent before any trial related activities are conducted, has good compliance and has agreed to follow-up.
排除标准
- •Treatment with chemotherapy, radiotherapy, immunotherapy or surgery (outpatient clinic surgery excluded) for metastatic disease
- •Symptomatic, untreated, or actively progressing CNS metastases(glucocorticoids or mannitol needed to control symptoms);
- •Significant cardiovascular disease(including congestive heart failure, angina pectoris, myocardial infarction or ventricular arrhythmia in the last 6 months);
- •is pregnant or breast feeding;
- •Malignant tumors in the past five years (except cured skin basal cell carcinoma and cervical carcinoma in situ).
- •History of autoimmune disease
- •Positive test for human immunodeficiency virus
- •Active hepatitis B or hepatitis C
- •Uncontrolled pleural effusion and ascites
- •Thyroid dysfunction.
研究组 & 干预措施
Cohort 1A
In this cohort, a patient would receive SHR6390(CDK4/6 inhibitor) combined with SHR1316 (anti-PD-L1) and endocrine therapy.
干预措施: SHR6390 (Drug)
Cohort 1A
In this cohort, a patient would receive SHR6390(CDK4/6 inhibitor) combined with SHR1316 (anti-PD-L1) and endocrine therapy.
干预措施: SHR-1316 (Drug)
Cohort 1A
In this cohort, a patient would receive SHR6390(CDK4/6 inhibitor) combined with SHR1316 (anti-PD-L1) and endocrine therapy.
干预措施: SERD (Drug)
Cohort 1A
In this cohort, a patient would receive SHR6390(CDK4/6 inhibitor) combined with SHR1316 (anti-PD-L1) and endocrine therapy.
干预措施: AI (Drug)
Cohort 1B
In this cohort, a patient would receive SHR6390(CDK4/6 inhibitor) combined with endocrine therapy.
干预措施: SHR6390 (Drug)
Cohort 1B
In this cohort, a patient would receive SHR6390(CDK4/6 inhibitor) combined with endocrine therapy.
干预措施: SERD (Drug)
Cohort 1B
In this cohort, a patient would receive SHR6390(CDK4/6 inhibitor) combined with endocrine therapy.
干预措施: AI (Drug)
Cohort 2A
In this cohort, a patient would receive SHR1316 (anti-PD-L1) combined with nab-paclitaxel.
干预措施: SHR-1316 (Drug)
Cohort 2A
In this cohort, a patient would receive SHR1316 (anti-PD-L1) combined with nab-paclitaxel.
干预措施: Nab paclitaxel (Drug)
Cohort 2B
In this cohort, a patient would single nab-paclitaxel.
干预措施: Nab paclitaxel (Drug)
Cohort 2C
In this cohort, a patient would receive SHR6390(CDK4/6 inhibitor) combined with fulvestrant.
干预措施: SHR-1316 (Drug)
Cohort 2C
In this cohort, a patient would receive SHR6390(CDK4/6 inhibitor) combined with fulvestrant.
干预措施: SERD (Drug)
结局指标
主要结局
PFS
时间窗: Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (approximately 5 years)
time to progressive disease (according to RECIST1.1)
次要结局
- ORR(Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (approximately 5 years))
- CBR(Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (approximately 5 years))
- OS(Randomization to death from any cause, through the end of study (approximately 5 years))