all trans retinoic acid combined with toripalimab+chemotherapy for locally advanced inoperable or metastatic triple negative breast cancer：a multi-center, multi-cohort phase ii trial

Conditions: Triple Negative Breast Cancer (TNBC)

Summary: all trans retinoic acid combined with toripalimab+chemotherapy for locally advanced inoperable or metastatic triple negative breast cancer：a multi-center, multi-cohort phase ii trial


Eligibility criteria:
inclusion criteria: 1. the subjects voluntarily participate and sign a written informed consent form; 2. age ≥ 18 years old; 3. for locally advanced inoperable or metastatic breast cancer confirmed by histology (according to ajcc 8th edition staging), the histology and pathology clearly showed that er, pr, her-2 were negative. if there was metastatic lesion pathology, the metastatic lesion histology and pathology should prevail. the definition of er and pr negativity is: ihc er\&lt;1%, ihc pr\&lt;1%. her-2 negativity is defined as: immunohistochemical detection of her-2 (-) or (1+), her-2 (2+) must undergo fish testing and the result is negative, her-2 (-) or (1+) can choose to undergo fish testing and the result is negative; 4. according to recist 1.1 criteria for solid tumor evaluation, there must be at least one measurable lesion; 5. cohort 1: for locally advanced non operable or metastatic tnbc that has not been previously treated, intravenous chemotherapy and anti-tumor therapy may be used during previous neoadjuvant and/or adjuvant therapy stages, provided that the interval between the end of neoadjuvant and/or adjuvant therapy and the occurrence of recurrence/metastasis is ≥ 12 months; cohort 2: local late stage inoperable or metastatic tnbc with previous treatment failures of at least one line or above; 6. all subjects should undergo tumor lesion biopsy during the screening period to obtain sufficient qualified tumor tissue specimens for retrospective biomarker analysis (including pd-l1 expression levels) in their cohort. if subjects are unable to undergo biopsy, they should provide tumor samples or unstained sections (3-5 μm) that have been fixed in formalin and embedded in paraffin (ffpe) closest to the start of the study treatment (up to 24 months) for corresponding biomarker analysis; 7. the main organ function is good, the relevant examination indicators within 14 days before treatment meet the following requirements: without blood transfusion, platelet count ≥ 100 × 10\^9/l, hemoglobin ≥ 90g/l, neutrophil count (anc) ≥ 1.5 × 10\^9/l ast and alt ≤ 2.5 x upper limit of normal (uln), ≤ 5 x uln if liver metastasis is present, total bilirubin ≤ 1.5 x uln, serum creatinine (cr) ≤ 1.5 uln, or creatinine clearance rate ≥ 60ml/min (cockcroft gault formula) 8. expected survival period ≥ 3 months; 9. ecog ps score: 0-1 points; 10. non surgical sterilization, male patients with women of childbearing age or partners of childbearing age, are required to use a medically approved contraceptive measure (such as intrauterine device, contraceptive pill, or condom) during the study treatment period and within 6 months after the end of the study treatment period; female patients of childbearing age who undergo non-surgical sterilization must have a negative serum hcg test within 72 hours prior to enrollment in the study. exclusion criteria: 1. individuals who have previously been treated with pd-1 or pd-l1 monoclonal antibodies; participants in cohort 1 who have previously used albumin paclitaxel; 2. individuals known to be allergic to any of the drugs in the study; 3. patients who have hypersensitivity reactions to other vitamin a drugs; 4. history of active autoimmune diseases requiring systemic treatment in the past 2 years (e.g. corticosteroids (dose ≤ 10mg/day, except for prednisone or other effective hormones) or immunosuppressive drugs); 5. diagnosed with immune deficiency or undergoing systemic steroid therapy (excluding doses ≤ 10mg/day of prednisone or other effective hormones) or any other form of immunosuppressive therapy within 7 days prior to enrollment; 6. there are other known malignant tumors that have progressed or require active treatment in the past 5 years. excluding malignant tumors that can be treated locally and have already been cured, such as skin basal cell carcinoma, skin squamous cell carcinoma, and cervical cancer in situ; 7. known to have active central nervous system (cns) metastases; 8. history of non infectious pneumonia requiring steroid hormone therapy; 9. active infections require systematic treatment; 10. there are serious uncontrolled hypertension, diabetes and hyperlipidemia; 11. history of ii-iv congestive heart failure or myocardial infarction within 6 months prior to enrollment; 12. individuals who tested positive for hiv during screening; 13. active hepatitis (hepatitis b reference: hbsag positive and hbv dna ≥ 500 iu/ml; hepatitis c reference: hcv antibody positive and hcv copy number\&gt;upper limit of normal value); 14. individuals with other serious acute or chronic physiological or mental problems; 15. accepting any medication that is prohibited from being used in combination with the investigational drug, unless the medication has been discontinued within 7 days prior to enrollment; 16. lactating women; 17. individuals who have participated in clinical trials of other anti-tumor drugs within the past four weeks; 18. inability to swallow, intestinal obstruction, or other factors that affect medication administration and absorption; 19. any situation that other researchers consider unsuitable for participation in this study.