Combining immune therapy with chemotherapy for advanced soft tissue sarcoma

Inclusion Criteria:

* Age 18 to 75 years, regardless of gender;
* Patients with histopathologically confirmed undifferentiated sarcoma (except small round cell undifferentiated sarcoma), synovial sarcoma, angiosarcoma, fibrosarcoma, smooth muscle sarcoma, liposarcoma (except well differentiated liposarcoma), pleomorphic rhabdomyosarcoma, malignant peripheral nerve sheath meningiomas, desmoplastic small round cell tumor, not other specified (NOS), SMARCA4-deficient sarcoma, malignant phyllodes tumor of the breast, intimal sarcoma.
* Patients with locally advanced disease that is not amenable to surgery/radiation therapy or with recurrent/metastatic disease;
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 to 1;
* Expected survival of more than 3 months;
* Within 7 days prior to screening (including day 7), laboratory test data requirements: neutrophil count ≥1.5×10⁹/L, platelet count ≥90×10⁹/L, hemoglobin ≥90g/L (no blood transfusion within 14 days), serum total bilirubin ≤1.5 times the upper limit of normal (ULN); ALT and AST ≤2.5× ULN (≤5× ULN for patients with liver metastases); serum creatinine ≤1.5× ULN or creatinine clearance rate ≥50ml/min;
* Presence of measurable lesions according to RECIST 1.1 criteria;
* The subject (or their legal representative/guardian) must sign an informed consent form, indicating that they understand the purpose of this study, are aware of the necessary procedures, and are willing to participate in this study.

Exclusion Criteria:

Any of the following conditions will result in exclusion from the study:

* Previous treatment for advanced soft tissue sarcoma, except for those who relapsed more than six months after adjuvant therapy with a cumulative dose of doxorubicin ≤300mg/m2;
* Received any experimental or anti - tumor drugs within 4 weeks prior to enrollment;
* Previously received any anti - PD - 1, anti - PD - L1, anti - PD - L2, anti - CD137, or anti - CTLA - 4 antibody treatment, or any other antibodies or drugs specifically targeting T - cell co - stimulation or checkpoint pathways;
* History of other tumors within the past five years, except for cured cervical cancer or skin basal cell carcinoma; for patients with post - radiation sarcoma, another primary tumor must have no recurrence or metastasis;
* Symptomatic brain or meningeal metastasis (unless the patient has been treated for more than 6 months, with negative imaging results within 4 weeks prior to enrollment, and stable tumor - related clinical symptoms at the time of enrollment);
* Clinically significant active bleeding;
* Pregnant or lactating women; women of childbearing potential who have not taken adequate contraceptive measures;
* Alcohol abuse or drug addiction;
* Patients with active autoimmune diseases or a history of such diseases that may recur (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulonephritis, etc.), or those at high risk (such as patients who have undergone organ transplantation and require immunosuppressive therapy). Autoimmune hypothyroidism requiring only hormone replacement therapy or skin diseases not requiring systemic treatment are excluded;
* Patients who need to receive systemic corticosteroids (equivalent to \>10mg prednisone/day) within 14 days prior to enrollment or during the study, or those who require other immunosuppressive drug treatment. The use of topical or inhaled corticosteroids, or short - term (≤7 days) use of corticosteroids for prevention or treatment of non - autoimmune, non - frequent allergic diseases is excluded;
* Failure of important organs or other severe diseases, including interstitial pneumonia, clinically significant coronary artery disease, cardiovascular disease, or myocardial infarction, congestive heart failure, unstable angina, symptomatic pericardial effusion, or unstable arrhythmia within 6 months prior to enrollment;
* History of human immunodeficiency virus infection, or other acquired or congenital immune deficiency diseases, or history of organ transplantation or stem cell transplantation;
* Patients with active chronic hepatitis B or active hepatitis C. HBV carriers, those with stable hepatitis B after drug treatment (DNA titer ≤10\^3 copies/ml), and those with cured hepatitis C (HCV RNA negative) are eligible for enrollment;
* Severe neurological or psychiatric history; severe infection; active disseminated intravascular coagulation, or other concomitant diseases that, in the opinion of the investigator, seriously endanger the safety of the patient or affect the patient's ability to complete the study.