IO Combined With AI as First-line Treatment for Patients With Soft Tissue Sarcoma(TAIS)

Tislelizumab Combined With Liposomal Doxorubicin and Ifosfamide as First-line Treatment for Patients With Specified Subtypes of Unresectable or Metastatic Soft Tissue Sarcoma: a Multi-center, Single-arm, Prospective Phase II Clinical Trial

This study will enroll patients with specific subtypes of unresectable or metastatic soft tissue sarcoma, and will combine tislelizumab with the standard chemotherapy of liposomal doxorubicin and ifosfamide to initially explore the efficacy and safety.

Soft tissue sarcoma is a type of malignant tumor originating from the mesenchymal tissue of soft tissues and visceral organs, and can occur in various parts of the human body. The incidence of soft tissue sarcoma accounts for about 1% of all adult malignant tumors and 15% of pediatric malignant tumors. Surgical resection is the cornerstone of soft tissue sarcoma treatment, but since soft tissue sarcomas often metastasize systemically, even early-stage cases can see lung metastasis. Except for solitary lung metastases, which still advocate surgical resection, the rest all require drug treatment, especially for the treatment of locally advanced or metastatic soft tissue sarcoma, systemic chemotherapy is the main means of clinical application.

Once soft tissue sarcoma metastasizes to a distant site, the prognosis is extremely poor, with a median survival time of less than 1 year. Clinical research results show that doxorubicin (ADM) is the basic and standard drug for the treatment of soft tissue sarcoma, and the combination of ADM and ifosfamide (IFO) (AI regimen) can increase the effective rate to 35%. The AI regimen is a commonly used first-line combination treatment for advanced soft tissue sarcoma.

Immune checkpoints have been approved by the FDA for the clinical treatment of various types of tumors. This study will enroll patients with specific subtypes of unresectable or metastatic soft tissue sarcoma, and will combine tislelizumab with the standard chemotherapy of liposomal doxorubicin and ifosfamide to initially explore the efficacy and safety.

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.