Cryoablation Combined With Tirelizumab and Bevacizumab in Liver Metastatic TNBC Patients Failed by Multiline Therapy

Inclusion Criteria:

• Histologically or Imageologically confirmed liver metastatic tnbc patients;
• Histologically confirmed diagnosis of TNBC characterized by estrogen receptor negative (ER-), progesterone receptor negative (PR-) and human epidermal growth factor-2receptor negative (HER2-);
• ≥ 2 prior lines systemic therapy;
• Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1);
• The patients show no signs of bile duct obstruction, and the bilirubin is below theupper limit of 1.5x normal value (ULN);
• Age ≥ 18 years on the day of signing the ICF (or the legal age of consent in thejurisdiction in which the study is taking place);
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• The functions of the patient's organs and blood system meet the requirements;
• Blood system function: absolute neutrophil count (ANC) ≥ 1.5 x 109 / L, platelet count ≥ 100 x 109 / L
• Renal function: estimated glomerular filtration rate or creatinine clearance > 50 ml /min / 1.73 M2
• Liver function: total bilirubin ≤ 1.5 x ULN, AST and alt ≤ 5 x ULN
• Estimated survival time ≥12 weeks.

Exclusion Criteria:

• The patient is currently receiving or has received irradiation or local treatment forthe target lesion in the past 3 weeks.
• The patient had previously received cryoablation.
• The patient received major surgery within 14 days before enrolling in the study.
• Palliative radiotherapy must be completed at least 2 weeks before enrolling in thestudy, and there is no plan for additional radiotherapy for the same lesion; ·Patientswhose AE caused by radiotherapy did not recover to ≤ CTCAE 1 degree
• The patient had metastatic brain lesions, including asymptomatic and well controlledlesions.
• Complicated with infection and requiring intravenous antibiotic treatment.
• The patient has any clinically significant disease or history that the investigatorbelieves may endanger the safety of the patient or the reliability of the studyresults.
• The patient has a history of any other malignancy unless the remission period exceeds 1 year. (do not exclude skin cancer, cervical cancer in situ, superficial bladdercancer, and breast cancer in radical treatment).
• Female patients are pregnant or breastfeeding.
• The patient received any trial drug within 14 days before receiving the first studydrug.
• The patient had undiminished or unstable severe toxicity (≥ CTCAE 4.0 grade 2) afterprevious use of another trial drug and / or previous cancer treatment, except anemia,weakness and hair loss.
• Patients are allergic to the test drug or any of its excipients.
• Patients are known to be HIV positive, have HCB, or have HBV infection and HBV DNAexceeds 2000 IU / ml.
• The patient has a known history of drug addiction in the past 1 year, because thissituation may lead to a high risk of non-compliance of the trial drug.
• The patient has known active or suspected autoimmune disease. Subjects who are in astable state and do not need systemic immunosuppressive therapy are allowed to beenrolled.
• Subjects requiring systemic treatment with corticosteroids (> 10mg / day prednisoneefficacy dose) or other immunosuppressants within 14 days before the administration ofthe study drug were allowed to inhale or locally use steroids and adrenal hormonereplacement with a dose > 10mg / day prednisone efficacy dose in the absence of activeautoimmune diseases.
• The patient had a baseline corrected QT interval QTc > 450 ms, or the patient hadknown QT prolongation syndrome, torsade de pointe ventricular tachycardia, symptomaticventricular tachycardia, unstable heart syndrome within 3 months before the screeningvisit, > grade 2 New York Heart Association heart failure, > grade 2 CanadianCardiovascular Association angina pectoris.