Triple-negative Breast Cancer
Conditions
Keywords
TNBC, Molecular Subtype, Precision Treatment, Platform Study
Brief summary
This is a Phase II, open-label, Single-center platform study research based on molecular subtypes to explore precision therapy in refractory triple-negative breast cancer.
Detailed description
This is a Phase II, open-label, Single-center platform study，Based on FUSCC four TNBC subtypes and the results of the previous FUTURE trial, the investigators designed this platform trial, which for combined the TNBC subtyping and genomic sequencing-guided precision targeted therapy for refractory metastatic TNBC patients. In this trial, refractory mTNBC patients eligible for inclusion can be divided into various precision treatment group according to molecular typing and subtyping to evaluate the efficacy and safety of multiple precision targeted treatment. The research therapy arm can be updated with the update of basic translational research in our center, especially the refinement of typing, the discovery of new targets and the development of novel targeted drugs.
Interventions
DRUGB1: TROP2 ADC
B1: an Trophoblast cell-surface antigen 2 (TROP2) ADC
DRUGB2: TROP2 ADC with Camrelizumab
B2: TROP2 ADC : an Trophoblast cell-surface antigen 2 (TROP2) ADC Camrelizumab: an anti-programmed death-1 (PD-1) antibody
DRUGC1: SHR-A1811
C1: an anti-HER2 antibody-drug conjugate (ADC)
DRUGC2: SHR-A1811 with BP102
C2: SHR-A1811: an anti-HER2 antibody-drug conjugate (ADC) BP102: a humanized recombinant monoclonal IgG1 antibody (biosimilar to bevacizumab)
DRUGD1: TROP2 ADC
D1: an Trophoblast cell-surface antigen 2 (TROP2) ADC
DRUGD2: TROP2 ADC with BP102
D2: TROP2 ADC : an Trophoblast cell-surface antigen 2 (TROP2) ADC BP102: a humanized recombinant monoclonal IgG1 antibody (biosimilar to bevacizumab)
DRUGE1: SHR-A1811
E1: an anti-HER2 antibody-drug conjugate (ADC)
DRUGF1: TROP2 ADC
F1: an Trophoblast cell-surface antigen 2 (TROP2) ADC
DRUGG1: SHR-A1811
G1: an anti-HER2 antibody-drug conjugate (ADC)
DRUGH1: TROP2 ADC
H1: an Trophoblast cell-surface antigen 2 (TROP2) ADC
DRUGE2: SHR-A1811 with everolimus
E1: SHR-A1811 an anti-HER2 antibody-drug conjugate (ADC) everolimus： an mTOR inhibitor
DRUGTQB2102 with TQB2868
TQB2102: an anti-HER2 antibody-drug conjugate (ADC) TQB2868: an anti-PD-1/TGF-β bispecific antibody in all-comer TNBC
DRUGA1: SHR-A1811
A1: an anti-HER2 antibody-drug conjugate (ADC)
DRUGA2: SHR-A1811 with Camrelizumab with famitinib
A2: SHR-A1811: an anti-HER2 antibody-drug conjugate (ADC) Camrelizumab: an anti-programmed death-1 (PD-1) antibody
Sponsors
Fudan University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Female aged ≥18 years; 2. TNBC invasive breast cancer confirmed by histology (specific definition: ER \<1% positive tumor cells by immunohistochemistry are defined as ER negative, PR \<1% positive tumor cells are defined as PR negative, 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; 3. Progression after at least one prior therapeutic regimens for advanced/metastatic TNBC 4. 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); 5. 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 10\^9 /L; PLT acuity 75 x 10\^9 /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); 6. 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; 7. ECOG score ≤1, and life expectancy ≥3 months; 8. 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; 9. Subjects volunteered to join the study, signed informed consent, had good compliance, and cooperated with follow-up.
Exclusion criteria
1. 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); 2. Uncontrolled central nervous system metastases (indicating symptomatic or symptomatic treatment with glucocorticoids or mannitol); 3. 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; 4. 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; 5. Underwent major surgery (except minor outpatient procedures, such as placement of vascular access) within 3 weeks of the first course of trial treatment; 6. Pregnant or lactating patients; 7. Malignancy (except basal cell carcinoma of the skin, which has been cured, and carcinoma in situ of the cervix) in the past 5 years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the completion of study (approximately 3 years) | The proportion of participants whose best outcome is complete remission or partial remission (according to RECIST1.1) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the completion of study (approximately 3 years) | Time to progressive disease (according to RECIST1.1) |
| Duration of Response (DoR) | Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the completion of study(approximately 3 years) | Duration of whose best outcome is complete remission or partial remission (according to RECIST1.1) |
| Disease Control Rate (DCR) | Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the completion of study(approximately 3 years) | The proportion of patients with the best overall response of CR, PR, or stable disease (SD) |
| 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) |
Countries
China
Contacts
CONTACTZhimin Shao, M.D.
CONTACTYin Liu, M.D.
PRINCIPAL_INVESTIGATORZhimin Shao, M.D.
Fudan University
Outcome results
None listed