Efficacy and Safety of Envafolimab Combined With Doxorubicin and Ifosfamide as First-line Treatment for Advanced Soft Tissue Sarcoma
Soft tissue sarcoma (STS) is a rare, highly heterogeneous malignancy with a poor prognosis. The standard first-line treatment for advanced patients is anthracyclines (doxorubicin, A) combined with ifosfamide (I, AI regimen), but the efficacy is limited, and some subtypes do not respond well. Immune checkpoint inhibitors (ICI) have shown potential in specific STS subtypes. Anthracyclines can induce immunogenic cell death and upregulate PD-L1, providing a theoretical basis for combined immunotherapy. Previous studies have shown that ICI combined with chemotherapy (such as pembrolizumab + doxorubicin) is more effective than chemotherapy alone. Envolizumab is the world's first subcutaneously injected PD-L1 single-domain antibody-Fc fusion protein, with significant advantages: (1) small molecular weight (\ 80kDa) and strong tissue penetration; (2) high stability and can be stored at room temperature; (3) convenient subcutaneous injection and good tolerability (Phase II study of MSI-H/dMMR solid tumors ORR 42.7%, grade 3-4 TEAE 15.5%). In 2022, the FDA granted orphan drug designation for the treatment of STS. This study aims to evaluate the efficacy (ORR, PFS, OS, etc.) and safety of Envolizumab combined with an AI regimen (doxorubicin + ifosfamide) as a first-line treatment for advanced STS.
⁃ Pathologically confirmed advanced soft tissue sarcoma with at least one measurable lesion.
⁃ No previous systemic treatment.
⁃ ≥18 years old; ECOG score: 0 or 1; expected survival time more than 3 months;
⁃ Major organ function within 7 days before treatment, meeting the following criteria:
‣ (1) Routine blood test criteria (without blood transfusion within 14 days):
• Hemoglobin (HB) ≥90g/L; ② Absolute neutrophil count (ANC) ≥1.5×109/L; ③ Platelet count (PLT) ≥80×109/L. (2) Biochemical examinations must meet the following criteria: ① Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN); ② Alanine aminotransferase (ALT) and aspartate aminotransferase AST ≤ 2.5 ULN. If liver metastasis is present, ALT and AST ≤ 5 ULN; ③ Serum creatinine (Cr) ≤ 1.5 ULN or creatinine clearance (CCr) ≥ 60ml/min; (3) Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ lower limit of normal (50%). 5. Women of childbearing age must agree to use contraceptive measures (such as intrauterine devices, birth control pills or condoms) during the study and within 6 months after the study; serum or urine pregnancy tests must be negative within 7 days before study enrollment, and the patients must not be breastfeeding; men must agree to use contraceptive measures during the study and within 6 months after the study.