Triple-negative breast cancer
Conditions
Interventions
Trial Group:Ivosidenib (AK112) 20 mg/kg intravenous infusion every two weeks for 12 doses (neoadjuvant phase) combined with chemotherapy: nab-paclitaxel (100 mg/m^2 once weekly) and carboplatin (AUC 1
surgery
adjuvant phase continues with ivosidenib (20 mg/kg every two weeks) for 14 doses
Sponsors
Fudan University Shanghai Cancer Center
Eligibility
Sex/Gender
Female
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Able to understand and voluntarily sign the written informed consent form, which must be signed before performing the specified study procedures required by the study. 2. Treatment-naïve female patients aged 18 to 75 years at the time of signing the informed consent form. 3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. 4. Breast cancer meeting the following criteria: (All pathological assessment data shall only accept the pathological diagnosis report from the study center or the review results by the study center based on non-study center pathological tissue specimens or slides) (1) Pathologically confirmed invasive breast cancer; (2) Immunohistochemistry testing indicates that both estrogen receptor (ER) and progesterone receptor (PR) are negative (i.e., the proportion of positively stained tumor cells among all tumor cells 1 cm; (6) Tumor clinical stage: Stage II (T1cN1M0/T2N0-1M0/T3N0M0) or Stage III (T1cN2-N3M0/T2N2-3M0/T3N1-3M0). 5. Good organ function determined by the following requirements: (1) Complete blood count (no blood transfusion or use of hematopoietic stimulating factors for correction within 7 days before screening): 1) Hemoglobin (Hb) >=90g/L; 2) Absolute neutrophil count (ANC) >=1.5×10^9/L; absolute lymphocyte count (LC) >=0.5×10^9/L; 3) Platelet count (PLT) >=100×10^9/L; 4) White blood cell count (WBC) >=3.0×10^9/L and =50mL/min (Cockcroft-Gault formula); 2) Urine protein =2+, then 24-hour urine protein quantification must show protein =28g/L. (4) Coagulation function: International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) =50%. 6. Female subjects of childbearing potential must undergo a serum pregnancy test within 3 days before the first dose, with a negative result. Subjects and their partners must agree to use highly effective contraception methods during the study period and within 180 days after the last administration of the investigational product.
Exclusion criteria
Exclusion criteria: 1.bilateral breast cancer; 2.Previous history of ductal carcinoma in situ ( DCIS ) or lobular carcinoma in situ ( LCIS ). 3.Previous history of invasive breast cancer or metastatic breast cancer; 4.Surgical resection biopsy of primary breast tumor or axillary metastatic lymph nodes was performed before signing the informed consent form; 5.Any malignant tumor was diagnosed within 5 years before signing the informed consent, excluding cured cervical carcinoma in situ and skin. Basal cell carcinoma or squamous cell carcinoma; 6.Within 1 year before signing the informed consent, they received systemic chemotherapy, systemic targeted therapy and local radiotherapy. 7.Previously received including but not limited to PD-1 / PD-L1 antibody, CTLA-4 antibody, or other tumor immunotherapy for PD-1 / PD-L1. 8.Systematic treatment with anthracyclines, taxanes or platinum drugs has been received for any malignant tumor. 9.There are immunodeficiency diseases, including primary immunodeficiency diseases ( such as genetic factors ) or secondary immunodeficiency diseases ( such as HIV infection or immunotherapy ). 10.There is any autoimmune disease or a history of previous autoimmune diseases that still need to be treated, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, rheumatic valvular heart disease, glomerulonephritis, etc. Hypothyroidism due to autoimmune thyroiditis and type I diabetes with controllable and stable blood glucose who only need hormone replacement therapy are not included. 11.Known or suspected interstitial pneumonia ; other moderate to severe lung diseases that may interfere with the detection or treatment of drug-related pulmonary toxicity and seriously affect respiratory function, including idiopathic pulmonary fibrosis, organizing pneumonia / occlusive bronchiolitis, etc. 12.Patients with severe cardiovascular and cerebrovascular diseases, including but not limited to NYHA standard ( grade III or higher ), or myocardial infarction or cerebrovascular accident ( cerebral ischemia, symptomatic cerebral infarction, etc. ) within 3 months before the first administration, or unstable arrhythmia or unstable angina pectoris with coronary artery disease within 1 month before the first administration, or congestive heart failure beyond the above standard, or symptomatic superior vena cava syndrome ; 13.Any arterial thromboembolism events, NCI CTCAE 5.0 version of grade 3 and above venous thromboembolism events, transient ischemic attack, cerebrovascular accident, hypertensive crisis or hypertensive encephalopathy occurred within 6 months before the first administration ; the current presence of hypertension and oral antihypertensive drug treatment after systolic blood pressure >= 160mmHg or diastolic blood pressure 100mmHg ; 14.To study the history of live attenuated vaccine vaccination within 28 days before the first study or to predict the need for live attenuated vaccine vaccination during the study period ; 15.Active hepatitis B ( defined as hepatitis B virus surface antigen [ HBsAg ] test results were positive and HBV-DNA detection value >= 500IU / ml ); 16.Hepatitis C ( defined as positive HCV-RNA test results ) ; 17.A history of tuberculosis infection or treatment within 1 year before signing informed consent ; 18.Within 28 days before the first administration, patients received major surgeries other than invasive diagnostic procedures, peripherally inserted central catheter ( PICC ) placement, intra
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pathological Complete Response Rate (pCR, ypT0/is ypN0); | — |
Secondary
| Measure | Time frame |
|---|---|
| Event-Free Survival (EFS);Disease-Free Survival (DFS);Distant Disease-Free Survival (DDFS);Objective Response Rate (ORR); | — |
Countries
China
Contacts
Public ContactShao Zhimin
Fudan University Shanghai Cancer Center
Outcome results
None listed