Precision Platform Study of HR+/ HER2-advanced Breast Cancer Based on SNF Typing (A Prospective, Open-label, Multi-center, Phase II Platform Study)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 620
- 试验地点
- 1
- 主要终点
- Overall response rate (ORR)
研究概览
简要总结
The purpose of this study is to establish a prospective, multi-center platform research based on clinical subtypes to explore precision therapy in patients hormone-receptor-positive HER2-negative advanced breast cancer who had previously used CDK4/6 inhibitors.
详细描述
Participants in this study were hormone-receptor-positive HER2-negative patients with advanced breast cancer who had previously used CDK4/6 inhibitors. Hormone receptor positive HER2 negative was defined as ER positive (IHC ER positive percentage > 10% or PR positive (IHC PR positive percentage > 10%) and HER2 negative (IHC-/+; Or IHC++ but FISH/CISH-).
The Department of Pathology and the Key Laboratory of Breast Cancer of Fudan University Shanghai Cancer Center conducted digital pathological typing of the biopsy pathology of metastatic lesions of all participants . If the pathology of metastatic lesions could not be obtained, the digital pathological typing was performed according to the pathology of primary lesions. According to the digital pathological types of biopsy tissue and peripheral blood ctDNA, the patients were divided into four precise subtypes: SNF1, SNF2, SNF3, and SNF4. At the same time, the negative control group was randomly set by subtype stratification at 2:1. In different SNF types, patients were divided into 7 subcohorts according to the genetic PANEL results.
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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female aged ≥18 years;
- •HR+/HER2- invasive breast cancer confirmed by histology (specific definition: ER >10% positive tumor cells by immunohistochemistry is defined as ER positive, PR >10% positive tumor cells is defined as PR positive, ER and/or PR positive is defined as HR positive; HER2 0-1+ or HER2 + but negative by FISH without amplification was defined as HER2 negative);
- •Locally advanced breast cancer (unable to undergo radical local treatment) or recurrent metastatic breast cancer;
- •HR+/HER2- advanced breast cancer patients who had previously received CDK4/6 inhibitor therapy;
- •At least one measurable lesion according to RECIST 1.1 (conventional CT scan ≥20 mm, spiral CT scan ≥10 mm, measurable lesion has not received radiotherapy);
- •The functions of the main organs are basically normal and meet the following conditions:
- •I. Blood routine examination criteria shall meet: HB ≥90 g/L (no blood transfusion within 14 days); The ANC acuity 1.5 x 109 / L; PLT acuity 75 x 109 / L; Ii. Biochemical tests should meet the following criteria: TBIL ≤1.5×ULN (upper limit of normal value); ALT and AST ≤3×ULN; If liver metastases were present, ALT and AST≤ 5×ULN; Serum Cr ≤1×ULN, endogenous creatinine clearance > 50 ml/min (Cockcroft-Gault formula);
- •They have not received radiotherapy, molecular targeted therapy, or surgery within 3 weeks before the start of the study, and have recovered from the acute toxicity of previous treatment (if surgery was performed, the wound has healed completely); No peripheral neuropathy or grade I peripheral neurotoxicity;
- •ECOG score ≤2, and life expectancy ≥3 months;
- •Fertile female subjects were required to use a medically approved contraceptive method during the study treatment period and for at least 3 months after the last use of the study drug;
- •Subjects volunteered to join the study, signed informed consent, had good compliance, and cooperated with follow-up.
排除标准
- •Radiotherapy (except for palliative causes), chemotherapy, and immunotherapy were used in the first 3 weeks of treatment, except bisphosphonate (which can be used for bone metastasis);
- •Uncontrolled central nervous system metastases (indicating symptomatic or symptomatic treatment with glucocorticoids or mannitol);
- •A history of clinically important or uncontrolled heart disease, including congestive heart failure, angina pectoris, myocardial infarction, or ventricular arrhythmia within the last 6 months;
- •Persistent grade 1 or higher adverse reactions caused by previous treatments. The exception to this is hair loss or something the researchers don't think should be ruled out. Such cases should be clearly documented in the investigator's notes;
- •Underwent major surgery (except minor outpatient procedures, such as placement of vascular access) within 3 weeks of the first course of trial treatment;
- •Pregnant or lactating patients; Malignancy (except basal cell carcinoma of the skin, which has been cured, and carcinoma in situ of the cervix) in the past 5 years.
研究组 & 干预措施
SNF3 3B:
Fluzoparib SHR3162 100 mg qd+Treatment of physician' choice
干预措施: Fluzoparib (Drug)
SNF3 3B:
Fluzoparib SHR3162 100 mg qd+Treatment of physician' choice
干预措施: TPC (Drug)
SNF4 4B:
Apatinib 250mg qd+Treatment of physician' choice
干预措施: TPC (Drug)
SNF1 1A: PIK3CA mutation
PIK3CA inhibitors +Aromatase inhibitors(Letrozole/Anastrozole/Exemestane, po, qd, specific dose (letrozole 2.5mg/ day; Anastrozole 1mg/ day, Exemestane 25mg/ day);Or fulvestrant, 500mg ,im, qm, followed by 500mg im 2 weeks after the first dose; Premenopausal: Goserelin 3.6mg IM every 4 weeks.
干预措施: PIK3CA inhibitor (Drug)
SNF1 1A: PIK3CA mutation
PIK3CA inhibitors +Aromatase inhibitors(Letrozole/Anastrozole/Exemestane, po, qd, specific dose (letrozole 2.5mg/ day; Anastrozole 1mg/ day, Exemestane 25mg/ day);Or fulvestrant, 500mg ,im, qm, followed by 500mg im 2 weeks after the first dose; Premenopausal: Goserelin 3.6mg IM every 4 weeks.
干预措施: Aromatase Inhibitors or Fulvestrant (Drug)
SNF1 1A: PIK3CA mutation
PIK3CA inhibitors +Aromatase inhibitors(Letrozole/Anastrozole/Exemestane, po, qd, specific dose (letrozole 2.5mg/ day; Anastrozole 1mg/ day, Exemestane 25mg/ day);Or fulvestrant, 500mg ,im, qm, followed by 500mg im 2 weeks after the first dose; Premenopausal: Goserelin 3.6mg IM every 4 weeks.
干预措施: Goserelin (Drug)
SNF1 1B: AKT pathway mutation
AKT pathway inhibitors +Aromatase inhibitors(Letrozole/Anastrozole/Exemestane, po, qd, specific dose (letrozole 2.5mg/ day; Anastrozole 1mg/ day, Exemestane 25mg/ day);Or fulvestrant, 500mg ,im, qm, followed by 500mg im 2 weeks after the first dose; Premenopausal: Goserelin 3.6mg IM every 4 weeks.
干预措施: AKT inhibitor (Drug)
SNF1 1B: AKT pathway mutation
AKT pathway inhibitors +Aromatase inhibitors(Letrozole/Anastrozole/Exemestane, po, qd, specific dose (letrozole 2.5mg/ day; Anastrozole 1mg/ day, Exemestane 25mg/ day);Or fulvestrant, 500mg ,im, qm, followed by 500mg im 2 weeks after the first dose; Premenopausal: Goserelin 3.6mg IM every 4 weeks.
干预措施: Aromatase Inhibitors or Fulvestrant (Drug)
SNF1 1B: AKT pathway mutation
AKT pathway inhibitors +Aromatase inhibitors(Letrozole/Anastrozole/Exemestane, po, qd, specific dose (letrozole 2.5mg/ day; Anastrozole 1mg/ day, Exemestane 25mg/ day);Or fulvestrant, 500mg ,im, qm, followed by 500mg im 2 weeks after the first dose; Premenopausal: Goserelin 3.6mg IM every 4 weeks.
干预措施: Goserelin (Drug)
SNF1 1C: without above mutation
Everolimus 10mg po qd+Aromatase inhibitors(Letrozole/Anastrozole/Exemestane, po, qd, specific dose (letrozole 2.5mg/ day; Anastrozole 1mg/ day, Exemestane 25mg/ day);Or fulvestrant, 500mg ,im, qm, followed by 500mg im 2 weeks after the first dose; Premenopausal: Goserelin 3.6mg IM every 4 weeks.
干预措施: Everolimus (Drug)
SNF1 1C: without above mutation
Everolimus 10mg po qd+Aromatase inhibitors(Letrozole/Anastrozole/Exemestane, po, qd, specific dose (letrozole 2.5mg/ day; Anastrozole 1mg/ day, Exemestane 25mg/ day);Or fulvestrant, 500mg ,im, qm, followed by 500mg im 2 weeks after the first dose; Premenopausal: Goserelin 3.6mg IM every 4 weeks.
干预措施: Aromatase Inhibitors or Fulvestrant (Drug)
SNF1 1C: without above mutation
Everolimus 10mg po qd+Aromatase inhibitors(Letrozole/Anastrozole/Exemestane, po, qd, specific dose (letrozole 2.5mg/ day; Anastrozole 1mg/ day, Exemestane 25mg/ day);Or fulvestrant, 500mg ,im, qm, followed by 500mg im 2 weeks after the first dose; Premenopausal: Goserelin 3.6mg IM every 4 weeks.
干预措施: Goserelin (Drug)
SNF2 2A
Treatment of physician' choice+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib 15mg po qd for 4 weeks as a cycle
干预措施: Carrelizumab (Drug)
SNF2 2A
Treatment of physician' choice+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib 15mg po qd for 4 weeks as a cycle
干预措施: Famitinib (Drug)
SNF2 2A
Treatment of physician' choice+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib 15mg po qd for 4 weeks as a cycle
干预措施: TPC (Drug)
SNF3 3A: Stratification of BRCA/PALB2 expression
Fluzoparib SHR3162 100mg po qd+Dalpiciclib 125mg po qd for 4 weeks as a cycle
干预措施: Fluzoparib (Drug)
SNF3 3A: Stratification of BRCA/PALB2 expression
Fluzoparib SHR3162 100mg po qd+Dalpiciclib 125mg po qd for 4 weeks as a cycle
干预措施: Dalpiciclib (Drug)
SNF4 4A: HER2 low
SHR-A1811
干预措施: SHR-A1811 (Drug)
The control arm
Treatment of Physicians' Choice (albumin-paclitaxel, capecitabine, vinorelbine, and irbribulin)
干预措施: TPC (Drug)
SNF4 4B:
Apatinib 250mg qd+Treatment of physician' choice
干预措施: Apatinib (Drug)
SNF1 1D: without above mutation
Everolimus 10mg po qd+Treatment of physician' choice
干预措施: Everolimus (Drug)
SNF1 1D: without above mutation
Everolimus 10mg po qd+Treatment of physician' choice
干预措施: TPC (Drug)
SNF1 1E: HER2 LOW
Everolimus 10mg po qd+SHR-A1811
干预措施: SHR-A1811 (Drug)
SNF1 1E: HER2 LOW
Everolimus 10mg po qd+SHR-A1811
干预措施: Everolimus (Drug)
SNF1 1F: HER2 zero
Everolimus 10mg po qd+SHR-A1921
干预措施: Everolimus (Drug)
SNF1 1F: HER2 zero
Everolimus 10mg po qd+SHR-A1921
干预措施: SHR-A1921 (Drug)
SNF2 2B: HER2 zero
SHR-A1921+Pd-1 mab (Carrelizumab 200mg Q2W)+bevacizumab 7.5mg po ivgt t for 3 weeks as a cycle
干预措施: Carrelizumab (Drug)
SNF2 2B: HER2 zero
SHR-A1921+Pd-1 mab (Carrelizumab 200mg Q2W)+bevacizumab 7.5mg po ivgt t for 3 weeks as a cycle
干预措施: SHR-A1921 (Drug)
SNF2 2B: HER2 zero
SHR-A1921+Pd-1 mab (Carrelizumab 200mg Q2W)+bevacizumab 7.5mg po ivgt t for 3 weeks as a cycle
干预措施: bevacizumab (Drug)
SNF2 2C:
HER3 -ADC+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib for 3 weeks as a cycle
干预措施: Carrelizumab (Drug)
SNF2 2C:
HER3 -ADC+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib for 3 weeks as a cycle
干预措施: Famitinib (Drug)
SNF2 2C:
HER3 -ADC+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib for 3 weeks as a cycle
干预措施: SHR-A2009 (Drug)
SNF2 2D:
Nectin4-ADC+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib for 3 weeks as a cycle
干预措施: Carrelizumab (Drug)
SNF2 2D:
Nectin4-ADC+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib for 3 weeks as a cycle
干预措施: Famitinib (Drug)
SNF2 2D:
Nectin4-ADC+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib for 3 weeks as a cycle
干预措施: SHR-A2102 (Drug)
SNF2 2E: HER2 low
SHR-A1811+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib for 3 weeks as a cycle
干预措施: Carrelizumab (Drug)
SNF2 2E: HER2 low
SHR-A1811+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib for 3 weeks as a cycle
干预措施: Famitinib (Drug)
SNF2 2E: HER2 low
SHR-A1811+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib for 3 weeks as a cycle
干预措施: SHR-A1811 (Drug)
SNF3 3C:
CDK4i（SHR-6209 PR2D+PARP1i（SHR-1167 PR2D）
干预措施: SHR-1167 (Drug)
SNF3 3C:
CDK4i（SHR-6209 PR2D+PARP1i（SHR-1167 PR2D）
干预措施: SHR-6209 (Drug)
SNF3 3D:
PARP1i（SHR-1167 PR2D)+Famitinib 5mg po qd for 4 weeks as a cycle
干预措施: Famitinib (Drug)
SNF3 3D:
PARP1i（SHR-1167 PR2D)+Famitinib 5mg po qd for 4 weeks as a cycle
干预措施: SHR-1167 (Drug)
SNF3 3E: HER2 low
PARP1i（SHR-1167 PR2D)+SHR-A1811 for 3 weeks as a cycle
干预措施: SHR-A1811 (Drug)
SNF3 3E: HER2 low
PARP1i（SHR-1167 PR2D)+SHR-A1811 for 3 weeks as a cycle
干预措施: SHR-1167 (Drug)
SNF3 3F: HER2 zero
PARP1i（SHR-1167 PR2D)+SHR-A1921 for 3 weeks as a cycle
干预措施: SHR-A1921 (Drug)
SNF3 3F: HER2 zero
PARP1i（SHR-1167 PR2D)+SHR-A1921 for 3 weeks as a cycle
干预措施: SHR-1167 (Drug)
SNF4 4C
Famitinib 20mg po qd
干预措施: Famitinib (Drug)
SNF4 4D
Sorafenib 0.4g bid
干预措施: Sorafenib (Drug)
SNF4 4E
Apatinib 500mg qd
干预措施: Apatinib (Drug)
SNF4 4F: HER2 low
Famitinib+SHR-A1811 for 3 weeks as a cycle
干预措施: Famitinib (Drug)
SNF4 4F: HER2 low
Famitinib+SHR-A1811 for 3 weeks as a cycle
干预措施: SHR-A1811 (Drug)
SNF4 4G
Famitinib+HER3-ADC for 3 weeks as a cycle
干预措施: Famitinib (Drug)
SNF4 4G
Famitinib+HER3-ADC for 3 weeks as a cycle
干预措施: SHR-A2009 (Drug)
SNF4 4H
Famitinib+Nectin4-ADC for 3 weeks as a cycle
干预措施: Famitinib (Drug)
SNF4 4H
Famitinib+Nectin4-ADC for 3 weeks as a cycle
干预措施: SHR-A2102 (Drug)
结局指标
主要结局
Overall response rate (ORR)
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 3 years)
The proportion of participants whose best outcome is complete remission or partial remission (according to RECIST1.1)
次要结局
- Clinical Benefit Rate (CBR)(Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (approximately 3 years)
- Progression Free Survival (PFS)(Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (approximately 3 years)])
- Overall Survival (OS)(Randomization to death from any cause, through the end of study (approximately 3 years))
- CTCAE scale (V5.0)(up to One Year during follow-up)
- Exploration of translational research markers(up to One Year during follow-up)