Envafolimab with doxorubicin and ifosfamide for advanced soft tissue sarcoma

Efficacy and Safety of Envafolimab Combined With Doxorubicin and Ifosfamide as First-line Treatment for Advanced Soft Tissue Sarcoma

This trial will test whether adding envafolimab to doxorubicin and ifosfamide helps people with advanced soft tissue sarcoma respond better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University (Academic / other)
• Drugs / interventions: prednisone, pembrolizumab, Envolizumab, chemotherapy, immunotherapy, doxorubicin
• Locations: 1 site (Hanzhong, Zhejiang)
• Trial ID: NCT07243626 on ClinicalTrials.gov

What this trial studies

This is a Phase 2 interventional trial testing subcutaneous envafolimab combined with standard doxorubicin-plus-ifosfamide chemotherapy in adults with previously untreated advanced soft tissue sarcoma and at least one measurable lesion. Participants receive scheduled cycles of the AI chemotherapy alongside regular envafolimab injections, with safety, lab tests, and radiographic tumor response monitored throughout treatment. The combination is based on the idea that anthracyclines can cause immunogenic cell death and increase PD-L1 expression, potentially enhancing the effect of PD-L1 blockade. The single-center study is conducted at the Second Affiliated Hospital, Zhejiang University School of Medicine and tracks objective responses and treatment-related adverse events.

Who should consider this trial

Good fit: Adults (≥18) with pathologically confirmed advanced soft tissue sarcoma, at least one measurable lesion, no prior systemic treatment, expected survival >3 months, and adequate blood, liver, kidney, and cardiac function are eligible.

Not a fit: Patients with STS subtypes that typically do not respond to immunotherapy, those who have received prior systemic therapy, or those with poor organ function or very limited life expectancy are unlikely to benefit.

Why it matters

Potential benefit: If successful, this combination could increase tumor response rates and extend progression-free and overall survival for some patients with advanced soft tissue sarcoma.

How similar studies have performed: Other studies combining PD-1/PD-L1 inhibitors with chemotherapy (for example pembrolizumab plus doxorubicin) have shown improved responses in some STS subtypes, but using envafolimab as a subcutaneous PD-L1 agent is a relatively new approach.

Eligibility criteria

Inclusion Criteria:

1. Pathologically confirmed advanced soft tissue sarcoma with at least one measurable lesion.
2. No previous systemic treatment.
3. ≥18 years old; expected survival time more than 3 months;
4. 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.

Exclusion Criteria:

1. Chondrosarcoma (CS), osteosarcoma (OS), Ewing's sarcoma, dermatofibrosarcoma protuberans (DFSP), and gastrointestinal stromal sarcoma (GIST) are excluded;
2. Pregnant or lactating women, or women of childbearing potential who are not using contraceptive measures;
3. Current severe, uncontrolled acute infection; or purulent or chronic infection with a persistent wound;
4. Presence of a second primary tumor (excluding basal cell carcinoma of the skin);
5. Participation in other drug clinical trials within 4 weeks;
6. Presence of severe heart disease, including congestive heart failure, uncontrolled high-risk arrhythmias, unstable angina, myocardial infarction, severe valvular heart disease, and refractory hypertension;
7. Suffering from uncontrolled neurological, psychiatric, or mental disorders, poor compliance, and inability to match the medication. Patients with uncontrolled primary brain tumors or central nervous system metastases and significant intracranial hypertension or neuropsychiatric symptoms are excluded.
8. Evidence of a hereditary bleeding diathesis or coagulopathy.
9. A history of severe allergic/anaphylactic reactions to humanized antibodies.
10. Diagnosed with immunodeficiency or receiving systemic glucocorticoids or any other form of immunosuppressive therapy within 14 days prior to the first dose of the study drug. Physiological doses of glucocorticoids (≤10 mg/day of prednisone or equivalent) are permitted.
11. Subjects with active, known, or suspected autoimmune diseases (e.g., interstitial pneumonitis, colitis, hepatitis, hypophysitis, vasculitis, nephritis, including but not limited to these diseases or syndromes) are excluded.

Where this trial is running

Hanzhong, Zhejiang

• Department of Medical Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China — Hanzhong, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Ying Dong

Conditions Soft Tissue Sarcoma