This is a Phase Ib/II, open-label, multi-center umbrella study evaluating the efficacy and safety of multiple targeted treatment in patients with refractory metastatic TNBC.The specific grouping of patients' depends on FUSCC 500+ gene panel testing and IHC subtype staining.
This is a Phase Ib/II, open-label, multi-center,umbrella study evaluating the efficacy and safety of multiple targeted treatment in patients with metastatic TNBC who had disease progression during or following standard treatment with chemotherapy(anthracyclines,taxanes,platinums, vinorelbine,capecitabine,and gemcitabine included).300-400 patients will be screened and eligible participants will enter different treatment arms according to their molecular subtype (IHC staining) and FUSCC 500+ gene panel testing results. These tests would be done on their rebiopsy tumor specimen. Specifically, as to TNBC molecular subtyping,FUSCC data identified the genomic aberrations that drive each TNBC subtype by applying an integrative analysis combining somatic mutation, copy number aberrations (CNAs) and gene expression profiles, which classified TNBC patients into four subtypes, namely luminal androgen receptor (LAR), immunomodulatory (IM), basal-like immune suppressed (BLIS), and mesenchymal-like (MES). Then, FUSCC conducted a IHC subtyping model to replace complex genomic sequencing, which have been validated in FUSCC cohort.FUSCC 500+ gene panel was developed combining public database(TCGA, METABRIC, 560WES, MSKCC-IMPACT ect.) and FUSCC private TNBC database.New treatment arms may be added and/or existing treatment arms may be closed during the course of the study on the basis of ongoing clinical efficacy and safety as well as the current treatments available.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
140
If patients were LAR subtype with HER2 gene activated mutation, she would receive pyrotinib(EGFR-TKI) 400mg qd and capecitabine 1000mg/m2 bid (d1-d14)
B1: if patients were LAR subtype without HER2 gene activated mutation, but had PI3KCA mutation, she would receive everolimus 10mg qd combined with AR inhibitor SHR3680 240mg qd continuously ; B2: if patients were LAR subtype without HER2 gene activated mutation or PI3KCA mutation, she would receive AR inhibitor SHR3680 240mg qd combined with CDK4/6 inhibitor SHR6390 150mg qd (three week on one week off); B4: If patients were LAR subtype without HER2 gene activated mutation or PI3KCA mutation, she would receive AR inhibitor SHR3680 240mg qd combined with EZH2 inhibitor SHR2554 300mg bid continuously
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, China
RECRUITINGObjective Response Rate (ORR)
The proportion of participants whose best outcome is complete remission or partial remission (according to RECIST1.1)
Time frame: 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)
Disease Control Rate(DOR)
Complete remission or partial remission or stable disease (according to RECIST1.1)
Time frame: Baseline through end of study (approximately 3 years)
Progression Free Survival(PFS)
time to progressive disease (according to RECIST1.1)
Time frame: 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)
time to death due to any cause
Time frame: Randomization to death from any cause, through the end of study (approximately 3 years)
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If patients were IM subtype, she will receive PD-1 antibody SHR1210 200mg q2w and nab-paclitaxel 100mg qw (three week on one week off).
If patients were BLIS subtype and had a BRCA gene pathogenic mutation, she will receive PARP inhibitor SHR3162 150mg bid and famitinib 20mg qd continuously .
If patients were BLIS subtype and did not have a BRCA gene pathogenic mutation , she will receive: E2: apatinib 250mg qd continuously combined with VP-16 50mg qd (three week on one week off); E3: famitinib 20mg qd continuously combined with VP-16 50mg qd (three week on one week off); E4: BP102 10mg/kg d1,d15 combined with nab-paclitaxel 100mg d1,d8,d,15; q4w
If patients were MES subtype and without PI3K/AKT pathway activation,she will receive famitinib 20mg qd continuously combined with VP-16 50mg qd (three week on one week off).
If patients were MES subtype and had PI3K/AKT pathway activation, she will receive mTOR inhibitor 10mg qd continuously combined with nab-paclitaxel 100mg qw (three week on one week off).