SNF Platform Study of HR+/ HER2-advanced Breast Cancer
- Conditions
- HER2-negative Breast CancerAdvanced Breast CancerBreast NeoplasmBreast CancerHormone Receptor Positive Tumor
- Interventions
- Drug: AKT inhibitorDrug: CarrelizumabDrug: SHR-1167Drug: TPCDrug: SHR-6209
- Registration Number
- NCT05594095
- Lead Sponsor
- Fudan University
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 620
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Female aged ≥18 years;
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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);
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Locally advanced breast cancer (unable to undergo radical local treatment) or recurrent metastatic breast cancer;
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HR+/HER2- advanced breast cancer patients who had previously received CDK4/6 inhibitor therapy;
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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);
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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);
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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;
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ECOG score ≤2, and life expectancy ≥3 months;
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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;
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Subjects volunteered to join the study, signed informed consent, had good compliance, and cooperated with follow-up.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description SNF1 1A: PIK3CA mutation PIK3CA inhibitor 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. SNF1 1A: PIK3CA mutation Aromatase Inhibitors or Fulvestrant 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. SNF1 1B: AKT pathway mutation AKT inhibitor 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. SNF1 1B: AKT pathway mutation Aromatase Inhibitors or Fulvestrant 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. SNF1 1D: without above mutation TPC Everolimus 10mg po qd+Treatment of physician' choice SNF1 1E: HER2 LOW SHR-A1811 Everolimus 10mg po qd+SHR-A1811 SNF1 1F: HER2 zero SHR-A1921 Everolimus 10mg po qd+SHR-A1921 SNF2 2B: HER2 zero Carrelizumab SHR-A1921+Pd-1 mab (Carrelizumab 200mg Q2W)+bevacizumab 7.5mg po ivgt t for 3 weeks as a cycle SNF2 2B: HER2 zero SHR-A1921 SHR-A1921+Pd-1 mab (Carrelizumab 200mg Q2W)+bevacizumab 7.5mg po ivgt t for 3 weeks as a cycle SNF2 2C: Carrelizumab HER3 -ADC+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib for 3 weeks as a cycle SNF2 2C: SHR-A2009 HER3 -ADC+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib for 3 weeks as a cycle SNF2 2D: Carrelizumab Nectin4-ADC+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib for 3 weeks as a cycle SNF2 2D: SHR-A2102 Nectin4-ADC+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib for 3 weeks as a cycle SNF2 2E: HER2 low Carrelizumab SHR-A1811+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib for 3 weeks as a cycle SNF2 2E: HER2 low SHR-A1811 SHR-A1811+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib for 3 weeks as a cycle SNF3 3C: SHR-1167 CDK4i（SHR-6209 PR2D+PARP1i（SHR-1167 PR2D） SNF3 3C: SHR-6209 CDK4i（SHR-6209 PR2D+PARP1i（SHR-1167 PR2D） SNF3 3D: Famitinib PARP1i（SHR-1167 PR2D)+Famitinib 5mg po qd for 4 weeks as a cycle SNF3 3D: SHR-1167 PARP1i（SHR-1167 PR2D)+Famitinib 5mg po qd for 4 weeks as a cycle SNF3 3E: HER2 low SHR-A1811 PARP1i（SHR-1167 PR2D)+SHR-A1811 for 3 weeks as a cycle SNF3 3E: HER2 low SHR-1167 PARP1i（SHR-1167 PR2D)+SHR-A1811 for 3 weeks as a cycle SNF3 3F: HER2 zero SHR-A1921 PARP1i（SHR-1167 PR2D)+SHR-A1921 for 3 weeks as a cycle SNF3 3F: HER2 zero SHR-1167 PARP1i（SHR-1167 PR2D)+SHR-A1921 for 3 weeks as a cycle SNF4 4C Famitinib Famitinib 20mg po qd SNF4 4D Sorafenib Sorafenib 0.4g bid SNF4 4F: HER2 low SHR-A1811 Famitinib+SHR-A1811 for 3 weeks as a cycle SNF4 4G SHR-A2009 Famitinib+HER3-ADC for 3 weeks as a cycle SNF4 4H SHR-A2102 Famitinib+Nectin4-ADC for 3 weeks as a cycle SNF1 1C: without above mutation Aromatase Inhibitors or Fulvestrant 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. SNF2 2A Carrelizumab Treatment of physician' choice+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib 15mg po qd for 4 weeks as a cycle SNF2 2A TPC Treatment of physician' choice+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib 15mg po qd for 4 weeks as a cycle SNF4 4A: HER2 low SHR-A1811 SHR-A1811 The control arm TPC Treatment of Physicians' Choice (albumin-paclitaxel, capecitabine, vinorelbine, and irbribulin) SNF3 3B: TPC Fluzoparib SHR3162 100 mg qd+Treatment of physician' choice SNF4 4B: TPC Apatinib 250mg qd+Treatment of physician' choice SNF1 1A: PIK3CA mutation Goserelin 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. SNF1 1B: AKT pathway mutation Goserelin 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. SNF1 1C: without above mutation Everolimus 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. SNF1 1C: without above mutation Goserelin 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. SNF3 3A: Stratification of BRCA/PALB2 expression Dalpiciclib Fluzoparib SHR3162 100mg po qd+Dalpiciclib 125mg po qd for 4 weeks as a cycle SNF3 3A: Stratification of BRCA/PALB2 expression Fluzoparib Fluzoparib SHR3162 100mg po qd+Dalpiciclib 125mg po qd for 4 weeks as a cycle SNF3 3B: Fluzoparib Fluzoparib SHR3162 100 mg qd+Treatment of physician' choice SNF4 4B: Apatinib Apatinib 250mg qd+Treatment of physician' choice SNF1 1D: without above mutation Everolimus Everolimus 10mg po qd+Treatment of physician' choice SNF1 1E: HER2 LOW Everolimus Everolimus 10mg po qd+SHR-A1811 SNF1 1F: HER2 zero Everolimus Everolimus 10mg po qd+SHR-A1921 SNF2 2B: HER2 zero bevacizumab SHR-A1921+Pd-1 mab (Carrelizumab 200mg Q2W)+bevacizumab 7.5mg po ivgt t for 3 weeks as a cycle SNF2 2E: HER2 low Famitinib SHR-A1811+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib for 3 weeks as a cycle SNF4 4E Apatinib Apatinib 500mg qd SNF4 4F: HER2 low Famitinib Famitinib+SHR-A1811 for 3 weeks as a cycle SNF4 4G Famitinib Famitinib+HER3-ADC for 3 weeks as a cycle SNF4 4H Famitinib Famitinib+Nectin4-ADC for 3 weeks as a cycle SNF2 2C: Famitinib HER3 -ADC+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib for 3 weeks as a cycle SNF2 2A Famitinib Treatment of physician' choice+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib 15mg po qd for 4 weeks as a cycle SNF2 2D: Famitinib Nectin4-ADC+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib for 3 weeks as a cycle
- Primary Outcome Measures
Name Time Method Overall response rate (ORR) 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)
- Secondary Outcome Measures
Name Time Method 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 the percentage of subjects with CR+PR+SD and last more than 24 weeks in all of the subjects
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)] time to progressive disease (according to RECIST1.1)
Overall Survival (OS) Randomization to death from any cause, through the end of study (approximately 3 years) time to death due to any cause
CTCAE scale (V5.0) up to One Year during follow-up To evaluate the rate of adverse effects of patient by the standard CTCAE scale (V5.0)
Exploration of translational research markers up to One Year during follow-up The collected subjects' tumor tissues, paracancerous tissues, blood, and fecal samples will be used for discovering exploratory biomarkers. The relationships between discovered biomarkers and subjects' disease status and treatment responses will also be investigated.
Trial Locations
- Locations (1)
Breast cancer institute of Fudan University Cancer Hospital
🇨🇳Shanghai, Shanghai, China