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

Plain English Summary

Efficacy and Safety of Envafolimab Plus Doxorubicin and Ifosfamide for Advanced Soft Tissue Sarcoma is a Phase 2 clinical trial sponsored by Second Affiliated Hospital, School of Medicine, Zhejiang University studying Soft Tissue Sarcoma. This trial tests a new combination of drugs, envafolimab with doxorubicin and ifosfamide, to treat advanced soft tissue sarcoma. It is for patients with advanced soft tissue sarcoma who have not received prior systemic treatment. Participation involves receiving the study drugs intravenously and regular check-ups. Standard chemotherapy (doxorubicin and ifosfamide) is the current alternative, but this trial explores adding a new immunotherapy drug. The trial aims to enroll 15 participants.

Official Summary

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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients with a confirmed diagnosis of advanced soft tissue sarcoma and at least one measurable tumor can join. Individuals who have not had any previous systemic treatment for their advanced sarcoma are eligible. Participants must be 18 years or older, have a good performance status (ECOG 0 or 1), and adequate organ function. Patients with certain specific types of sarcoma (like chondrosarcoma, osteosarcoma, Ewing's sarcoma, DFSP, GIST) or those with active autoimmune diseases or severe heart conditions cannot participate. This trial is studying Soft Tissue Sarcoma, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

Progression-free survival measures how long patients live without their cancer getting worse, indicating how well the new treatment controls the disease. The specific primary outcome measures are: Efficcy-Progression-free survival (From enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses the limited efficacy of current first-line treatments for advanced soft tissue sarcoma by investigating a novel combination of chemotherapy and immunotherapy. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Soft Tissue Sarcoma, where improved treatment options are needed.

Investor Insight

This trial targets a rare cancer with limited treatment options, potentially offering a new therapeutic avenue and representing an investment in novel immunotherapy combinations for challenging malign Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific risks and benefits of envafolimab, doxorubicin, and ifosfamide. Understand the schedule of infusions and follow-up appointments. Be prepared for regular blood tests and imaging scans to monitor your response and any side effects. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 15 participants

Interventions

• DRUG: Envafolimab combined with an AI regimen (doxorubicin and ifosfamide) — Envafolimab combined with an AI regimen: liposomal doxorubicin 35 mg/m² on day 1; IFO 2.5 mg/m² on days 1-3, intravenous infusion, every 3 weeks.

Primary Outcomes

• Efficcy-Progression-free survival (From enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months)

Secondary Outcomes

• Efficcy-Objective response rate (From enrollment to the end of treatment at 8 weeks)
• Efficcy-Disease control rate (From enrollment to the end of treatment at 8 weeks)
• Efficcy-overall survival (From enrollment until the date of death from any cause, assessed up to 60 months)
• adverse events-safety (From enrollment to the end of treatment at 8 weeks)

Full 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; ECOG score: 0 or 1; 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.

Trial Locations

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

Frequently Asked Questions

Related Conditions

• Soft Tissue Sarcoma
• Sarcoma
• Cancer
• Malignancy
• Oncology
• Chemotherapy
• Immunotherapy
• Advanced Cancer
• Rare Cancers
• Gastrointestinal Stromal Tumor (GIST)

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