Soft Tissue SarcomaPhase 2NCT07243626
Efficacy and Safety of Envafolimab Plus Doxorubicin and Ifosfamide for Advanced Soft Tissue Sarcoma
A Phase 2 study testing Envafolimab combined with an AI regimen (doxorubicin and ifosfamide) in people with Soft Tissue Sarcoma, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Soft Tissue Sarcoma
- What is being tested?
- Envafolimab combined with an AI regimen (doxorubicin and ifosfamide)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteChina
- Study dates
- 30 Sep 2024to 1 Jun 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically confirmed advanced soft tissue sarcoma with at least one measurable lesion.
- No previous systemic treatment.
- ≥18 years old; expected survival time more than 3 months;
- Major organ function within 7 days before treatment, meeting the following criteria:
- 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.
Who cannot join
- Chondrosarcoma (CS), osteosarcoma (OS), Ewing's sarcoma, dermatofibrosarcoma protuberans (DFSP), and gastrointestinal stromal sarcoma (GIST) are excluded;
- Pregnant or lactating women, or women of childbearing potential who are not using contraceptive measures;
- Current severe, uncontrolled acute infection; or purulent or chronic infection with a persistent wound;
- Presence of a second primary tumor (excluding basal cell carcinoma of the skin);
- Participation in other drug clinical trials within 4 weeks;
- Presence of severe heart disease, including congestive heart failure, uncontrolled high-risk arrhythmias, unstable angina, myocardial infarction, severe valvular heart disease, and refractory hypertension;
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- 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.
- Evidence of a hereditary bleeding diathesis or coagulopathy.
- A history of severe allergic/anaphylactic reactions to humanized antibodies.
- 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.
- 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 and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Department of Medical Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
Hanzhong, Zhejiang, 310009
Ying Dong, （0571）87783730, dongying74@zju.edu.cn
About this study
Official title: 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.
Read the detailed description
Soft tissue sarcoma (STS) encompasses a diverse group of rare, high-grade malignancies originating from mesenchymal tissues, exhibiting significant heterogeneity in histology, molecular characteristics, and clinical behavior. The prognosis for advanced or metastatic STS remains generally poor, underscoring the urgent need for more effective therapeutic strategies. Currently, the standard first-line treatment for advanced STS involves chemotherapy regimens comprising anthracyclines, primarily doxorubicin, often combined with ifosfamide (the AI regimen). While these regimens can induce tumor responses, their overall efficacy is limited, with modest response rates and survival benefits. Moreover, certain STS subtypes demonstrate resistance to conventional chemotherapy, highlighting the necessity for novel and combination treatment approaches.
Recent advances in immunotherapy, particularly immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 pathways, have opened new avenues for treating specific STS subtypes. Evidence suggests that anthracyclines, such as doxorubicin, can induce immunogenic cell death, enhance tumor antigen presentation, and upregulate PD-L1 expression, creating a compelling rationale for combining chemotherapy with immunotherapy. Indeed, clinical studies have demonstrated that combining ICIs like pembrolizumab with chemotherapy regimens can improve objective response rates (ORR), progression-free survival (PFS), and overall survival (OS) compared to chemotherapy alone in certain patient populations.
Envolizumab represents a groundbreaking development in the realm of immunotherapeutics. As the world's first subcutaneously injectable PD-L1 single-domain antibody-Fc fusion protein, it boasts several distinct advantages: a small molecular weight (~80 kDa) that ensures superior tissue penetration, high stability with room temperature storage capability, and a convenient subcutaneous administration route that enhances patient tolerability and adherence. Phase II clinical data have demonstrated promising anti-tumor activity in MSI-H/dMMR solid tumors, with an ORR of 42.7%, and an acceptable safety profile, with grade 3-4 treatment-emergent adverse events (TEAEs) in only 15.5% of patients. Notably, in 2022, the FDA granted orphan drug designation to Envolizumab for the treatment of STS, highlighting its potential as a novel therapeutic option.
This study aims to systematically evaluate the efficacy and safety of combining Envolizumab with the AI chemotherapy regimen as a first-line treatment for patients with advanced STS. The primary endpoint will focus on the overall response rate (ORR), with secondary endpoints including disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety profile assessments. The study hypothesizes that this combination could synergistically enhance anti-tumor immune responses, improve clinical outcomes, and offer a more tolerable treatment option for patients with advanced STS. The findings could potentially establish a new standard of care and provide critical insights into the integration of immunotherapy and chemotherapy in the management of this challenging malignancy.
- Conditions
- Soft Tissue Sarcoma
- Being tested
- Envafolimab combined with an AI regimen (doxorubicin and ifosfamide)
- Medical subject headings
- Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Envafolimab combined with an AI regimen (doxorubicin and ifosfamide)Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| intervention | Experimental | Eligible patients with soft tissue sarcoma were enrolled and treated with Envafolimab 300 mg/dose subcutaneously every 3 weeks on day 1. The AI regimen consisted of liposomal doxorubicin 35 mg/m² on day 1 and intravenous infusion of IFO 2.5 mg/m² on days 1-3, every 3 weeks. Efficacy and safety were assessed approximately every 6 weeks (42 ± 7 days). Patients with disease control (CR+PR+SD) and tolerable adverse reactions could choose continue treatment until disease progression, unacceptable toxicity, or discontinuation at the investigator's discretion. Receives: Drug: Envafolimab combined with an AI regimen (doxorubicin and ifosfamide) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficcy-Progression-free survival
PFS
Measured: 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 (5)
Efficcy-Objective response rate
Objective response rate(ORR) =CR+PR
Measured: From enrollment to the end of treatment at 8 weeks
Efficcy-Disease control rate
DCR=CR+PR+SD
Measured: From enrollment to the end of treatment at 8 weeks
Efficcy-overall survival
OS
Measured: From enrollment until the date of death from any cause, assessed up to 60 months
adverse events-safety
adverse events
Measured: From enrollment to the end of treatment at 8 weeks
Efficacy: 1-year os rate
the estimated percentage of patients who remain alive
Measured: From enrollment to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2025
- Study start30 Sep 2024
- Primary completion30 Dec 2026 (estimated)
- Study completion1 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Soft Tissue SarcomaStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital, Zhejiang University, School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07243626
- Sponsor's protocol ID
- IR2023375
- Status last verified
- Sep 2025
- First submitted
- 24 Sep 2025
- Last updated
- 24 Apr 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: only IPD used in the results publication
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Envafolimab Combined With Doxorubicin and Ifosfamide as First-line Treatment for Advanced Soft Tissue Sarcoma
- ClinicalTrials.gov ID
- NCT07243626
- Acronym / sponsor ID
- IR2023375
- Conditions
- Soft Tissue Sarcoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Study start
- 30 Sep 2024 (actual)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 1 Jun 2027 (estimated)
- First posted
- 24 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Soft tissue sarcoma (STS) encompasses a diverse group of rare, high-grade malignancies originating from mesenchymal tissues, exhibiting significant heterogeneity in histology, molecular characteristics, and clinical behavior. The prognosis for advanced or metastatic STS remains generally poor, underscoring the urgent need for more effective therapeutic strategies. Currently, the standard first-line treatment for advanced STS involves chemotherapy regimens comprising anthracyclines, primarily doxorubicin, often combined with ifosfamide (the AI regimen). While these regimens can induce tumor responses, their overall efficacy is limited, with modest response rates and survival benefits. Moreover, certain STS subtypes demonstrate resistance to conventional chemotherapy, highlighting the necessity for novel and combination treatment approaches.
Recent advances in immunotherapy, particularly immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 pathways, have opened new avenues for treating specific STS subtypes. Evidence suggests that anthracyclines, such as doxorubicin, can induce immunogenic cell death, enhance tumor antigen presentation, and upregulate PD-L1 expression, creating a compelling rationale for combining chemotherapy with immunotherapy. Indeed, clinical studies have demonstrated that combining ICIs like pembrolizumab with chemotherapy regimens can improve objective response rates (ORR), progression-free survival (PFS), and overall survival (OS) compared to chemotherapy alone in certain patient populations.
Envolizumab represents a groundbreaking development in the realm of immunotherapeutics. As the world's first subcutaneously injectable PD-L1 single-domain antibody-Fc fusion protein, it boasts several distinct advantages: a small molecular weight (~80 kDa) that ensures superior tissue penetration, high stability with room temperature storage capability, and a convenient subcutaneous administration route that enhances patient tolerability and adherence. Phase II clinical data have demonstrated promising anti-tumor activity in MSI-H/dMMR solid tumors, with an ORR of 42.7%, and an acceptable safety profile, with grade 3-4 treatment-emergent adverse events (TEAEs) in only 15.5% of patients. Notably, in 2022, the FDA granted orphan drug designation to Envolizumab for the treatment of STS, highlighting its potential as a novel therapeutic option.
This study aims to systematically evaluate the efficacy and safety of combining Envolizumab with the AI chemotherapy regimen as a first-line treatment for patients with advanced STS. The primary endpoint will focus on the overall response rate (ORR), with secondary endpoints including disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety profile assessments. The study hypothesizes that this combination could synergistically enhance anti-tumor immune responses, improve clinical outcomes, and offer a more tolerable treatment option for patients with advanced STS. The findings could potentially establish a new standard of care and provide critical insights into the integration of immunotherapy and chemotherapy in the management of this challenging malignancy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| intervention | Experimental | Drug: Envafolimab combined with an AI regimen (doxorubicin and ifosfamide)Eligible patients with soft tissue sarcoma were enrolled and treated with Envafolimab 300 mg/dose subcutaneously every 3 weeks on day 1. The AI regimen consisted of liposomal doxorubicin 35 mg/m² on day 1 and intravenous infusion of IFO 2.5 mg/m² on days 1-3, every 3 weeks. Efficacy and safety were assessed approximately every 6 weeks (42 ± 7 days). Patients with disease control (CR+PR+SD) and tolerable adverse reactions could choose continue treatment until disease progression, unacceptable toxicity, or discontinuation at the investigator's discretion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Pathologically confirmed advanced soft tissue sarcoma with at least one measurable lesion.
- No previous systemic treatment.
- ≥18 years old; expected survival time more than 3 months;
- Major organ function within 7 days before treatment, meeting the following criteria:
- Routine blood test criteria (without blood transfusion within 14 days):
Key exclusion criteria (11 listed)
- Chondrosarcoma (CS), osteosarcoma (OS), Ewing's sarcoma, dermatofibrosarcoma protuberans (DFSP), and gastrointestinal stromal sarcoma (GIST) are excluded;
- Pregnant or lactating women, or women of childbearing potential who are not using contraceptive measures;
- Current severe, uncontrolled acute infection; or purulent or chronic infection with a persistent wound;
- Presence of a second primary tumor (excluding basal cell carcinoma of the skin);
- Participation in other drug clinical trials within 4 weeks;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | intervention |
Primary outcome
Efficcy-Progression-free survival
Time frame: From enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
PFS
5 secondary outcomes
Efficcy-Objective response rate
Time frame: From enrollment to the end of treatment at 8 weeks
Efficcy-Disease control rate
Time frame: From enrollment to the end of treatment at 8 weeks
Efficcy-overall survival
Time frame: From enrollment until the date of death from any cause, assessed up to 60 months
adverse events-safety
Time frame: From enrollment to the end of treatment at 8 weeks
Efficacy: 1-year os rate
Time frame: From enrollment to 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2026.
- Individual participant dataSharing planned: Yes. only IPD used in the results publication
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Envafolimab combined with an AI regimen (doxorubicin and ifosfamide) in people with Soft Tissue Sarcoma, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ying Dong (+8113666669105, dongying74@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficcy-Progression-free survival (time frame: From enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2026.