High-risk GD2 Positive Ewing SarkomaPhase 1NCT06839703
International Phase I Trial of Dinutuximab Beta With VDC/IE in GD2-Positive Ewing Sarkoma
A Phase 1 study testing Dinutuximab beta in people with High-risk GD2 Positive Ewing Sarkoma, run by Prof. Dr. Dr. Birgit Burkhardt at 5 sites in Germany.
Trial summary
The goal of the study is to investigate the feasibility, toxicity, and biological activity of the treatment with dinutuximab beta in combination with standard chemotherapy in EWS to give high-risk patients with a GD2 positiv pumor a benefit in treatment. Read more about this study
- Who is it for?
- Ages 12 months and older
- Conditions the study is for
- High-risk GD2 Positive Ewing Sarkoma
- What is being tested?
- Dinutuximab beta
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 5 sitesGermany
- Study dates
- 16 May 2025to 1 Mar 2027
- Phase
- Phase 1
- 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 12 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Histologically confirmed, newly diagnosed Ewing Sarcoma (m/f/d) or so-called Ewing-like sarcoma (i.e. translocation-positive small blue round cell sarcoma other than Rhabdomyosarcoma) of bone and / or soft tissue with evidence of EWS translocation by fluorescence in situ hybridization (FISH), real-time polymerase chain reaction (RT-PCR), or next-generation sequencing (NGS) assay
- High risk stratification (metastatic disease)
- Centrally confirmed GD2-positive tumor (biopsy of original and/or residual tumor or liquid biopsy in peripheral blood)
- Availability of fresh frozen tumor tissue for central GD2-detection
- Age ≥12 months
- Start of first line treatment according to standard induction treatment (Cycle 1-4: VDC - IE - VDC - IE)
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- Wash-out phase with a minimum of 14 days after the last the dose of the last chemotherapy
- Lansky (<16 years) Performance Score ≥70% or ECOG (≥16 years) ≤ 2
- Adequate bone marrow function as evidenced by meeting all the following requirements:
- White blood cell count > 2000/μl
- ANC ≥1000 cells/μL (G-CSF allowed)
- Platelet count 75,000 cells/μL without the use of platelet transfusion within the last 2 days
- Hemoglobin ≥9 g/dL without the use of red blood cell transfusion within the last 2 days
- Adequate hepatic function as evidenced by meeting all the following requirements:
- Serum total bilirubin ≤1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 x ULN
- Adequate cardiac function: confirmed by echocardiography with a left ventricular ejection fraction (LVEF) of ≥ 50%
- Adequate renal function: creatinine clearance or glomerular filtration rate (GFR) > 60 mL/min/1.73 m2
- No known active HIV, HBV, or HCV infection
- No severe neurological impairment, particularly no motor or sensory deficits, except for neurological deficits caused by Ewing sarcoma
- Female patients of childbearing potential must present with a negative serum pregnancy test and agree to employ adequate birth control measures for the duration of the study and until 3 months after the end of treatment. Female patients who are lactating must agree to stop breast-feeding from the start of study treatment until 1 month after the end of treatment.
- Patient or their legal representative is willing and able to comply with the requirements of the study protocol
Who cannot join
- Relapsed or refractory Disease state
- Patients with hypersensitivity against at least 1 component of the investigational medicinal product
- Significant illnesses and/or any of the following:
- significant psychiatric disabilities or uncontrolled seizure disorders
- active uncontrolled peptic ulcer disease
- clinically significant neurologic deficit or objective peripheral neuropathy
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- clinically significant, symptomatic fluid in a third space
- Active and uncontrolled CNS metastases (indicated by clinical symptoms, cerebral edema, corticosteroid and/or anticonvulsant requirement, or progressive disease); for controlled CNS metastases, patient should have been off corticosteroids for at least 28 days without overt evidence of significant neurological deficits prior to enrollment
- Significant cardiac conduction abnormalities, including known familial prolonged QT syndrome, or screening QTc >480 msec
- Active, uncontrolled infection or an unexplained fever >38.5°C which in the Investigator's opinion might compromise the patient's participation in the study or affect the study outcome
- Chronic Grade ≥2 diarrhea
- Diagnosis of any malignancy other than the disease under study
- Any other medical or social condition deemed by the Investigator to be likely to interfere with a patient's ability to cooperate and participate in the study or interfere with the interpretation of the results.
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
Germany5 sites, 5 recruiting
- Not yet recruiting
Helios Kliniken Berlin-Buch
Berlin, State of Berlin, 13125
Patrick Hundsdörfer
- Recruiting
Universitätsmedizin Essen
Essen, North Rhine-Westfalia, 45147
Uta Dirksen
- Recruiting
Universitätsmedizin Göttingen
Göttingen, Lower Saxony, 37075
Christof Kramm
- Not yet recruiting
Universitätsmedizin Greifswald
Greifswald, Mecklenburg-Vorpommern, 17475
- Recruiting
Universitätsmedizin der Johannes Gutenberg-Universität
Mainz, Rhineland-Palatinate, 55131
Arthur Wingerter
About this study
Official title: International Open-label Phase I Dose Escalation Study of Dinutuximab Beta in Combination With Vincristine/Doxorubicin/Cyclophosphamide and Ifosfamide/Etoposide in Pediatric, Adolescent, and Adult Patients With GD2-positive Ewing Sarcoma
The goal of the study is to investigate the feasibility, toxicity, and biological activity of the treatment with dinutuximab beta in combination with standard chemotherapy in EWS to give high-risk patients with a GD2 positiv pumor a benefit in treatment. Within the study is tested with three different dosages in a 3+3 design with three pre-defined dose levels.
Read the detailed description
Immunotherapeutic approaches have emerged as an effective therapeutic approach in cancer. We will investigate the cell-surface ganglioside GD2 as a target since it is expressed on the cell surface of Ewing Sarcoma cells and clinical trials support the safety and efficacy of anti-GD2 antibodies in pediatric solid cancers.
Dinutuximab beta is a chimeric antibody that targets the disialoganglioside GD2. GD2 is expressed on a number of solid malignancies and was clinically investigated in pediatric patients with neuroblastoma. Expression in normal tissues is restricted to cerebellar neurons, skin melanocytes and peripheral pain fibers. Due to this expression pattern, anti-GD2 antibodies have been studied as targeted immunotherapy for neuroblastoma. With the results of these clinical trials, combination therapies with dinutuximab beta became a standard component of high-risk neuroblastoma therapy. GD2 expression is found in several EWS samples with variable expression-levels, and it is expected that anti-GD2 treatment is best suited as biomarker-driven approach.
The administration of vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide (VDC/IE) has been shown to be an effective systemic therapy and is therefore currently part of the standard treatment in Ewing Sarcoma. The international newest standard induction chemotherapy in the standard- and high-risk group consists of alternating VDC/IE. High-risk patients with a GD2 positive tumor could benefit from an addition of dinutuximab beta to the standard chemotherapy with VDC/IE.
The rationale for this trial is to investigate the feasibility, toxicity, and biological activity of dinutuximab beta in combination with standard chemotherapy in EWS.
This is a multi-center, phase 1, open-label, dose escalation study enrolling high-risk Ewing sarcoma patients that have been tested with GD2-positivity in a classical 3+3 design.
The decision to initiate treatment with 50% of the approved dosage for neuroblastoma in this dose-escalation study is grounded in both scientific literature and safety considerations. Starting at a lower dosage allows for the careful monitoring of patient response and minimizes the risk of adverse effects, particularly in a dose-sensitive adult population.
A risk assessment further supports this approach, indicating that starting at 50% of the approved neuroblastoma dose provides a safe baseline from which to escalate. The assessment outlines that a stepwise increase to 75% and subsequently to 100% of the approved dose allows for the identification of any dose-limiting toxicities (DLTs) in a controlled manner, thus optimizing patient safety.
The choice of 100 mg/m2 as the maximum dosage per cycle, equivalent to the dosage used in standard neuroblastoma treatment, is justified by its established efficacy and safety profile in this specific indication. The literature supports that doses up to 100 mg/m2 per cycle are well-tolerated in the majority of patients, with the therapeutic benefits outweighing the risks when administered within a carefully monitored clinical framework.
- Conditions
- High-risk GD2 Positive Ewing Sarkoma
- Being tested
- Dinutuximab beta
- Keywords
- Biomarker, GD2 expression, targeted therapy, high-risk Ewing Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dinutuximab betaDrug
Dinutuximab beta is added in different dosages to the standard chemotherapy
| Study group | Role | What they receive |
|---|---|---|
| dinutuximab beta added to standard chemotherapy | Experimental | Dinutuximab beta is added in different dosages to the standard chemotherapy Receives: Drug: Dinutuximab beta |
What is being measured
The primary outcome is the main question the study is designed to answer.
GD2 Positivity
local assessment for GD2 positivity
Measured: after initial diagnosis and before study enrolment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2025
- Study start16 May 2025
- Primary completion1 Mar 2027 (estimated)
- Study completion1 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for High-risk GD2 Positive Ewing SarkomaStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a multi-center, phase 1, open-label, dose escalation study enrolling high-risk Ewing sarcoma patients that have been tested with GD2-positivity in a classical 3+3 design.
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Prof. Dr. Dr. Birgit Burkhardt
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Prof. Dr. Dr. Birgit Burkhardt, German Society for Pediatric Oncology and Hematology GPOH gGmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06839703
- Sponsor's protocol ID
- CESS-GD2
- Status last verified
- Oct 2026
- First submitted
- 17 Feb 2025
- Last updated
- 2 Nov 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- International Open-label Phase I Dose Escalation Study of Dinutuximab Beta in Combination With Vincristine/Doxorubicin/Cyclophosphamide and Ifosfamide/Etoposide in Pediatric, Adolescent, and Adult Patients With GD2-positive Ewing Sarcoma
- ClinicalTrials.gov ID
- NCT06839703
- Acronym / sponsor ID
- CESS-GD2
- Conditions
- High-risk GD2 Positive Ewing Sarkoma
- Keywords
- Biomarker, GD2 expression, targeted therapy, high-risk Ewing Sarcoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Prof. Dr. Dr. Birgit BurkhardtUniversity, hospital or other
- Study start
- 16 May 2025 (actual)
- Primary completion
- 1 Mar 2027 (estimated)
- Study completion
- 1 Mar 2027 (estimated)
- First posted
- 21 Feb 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.
The goal of the study is to investigate the feasibility, toxicity, and biological activity of the treatment with dinutuximab beta in combination with standard chemotherapy in EWS to give high-risk patients with a GD2 positiv pumor a benefit in treatment. Within the study is tested with three different dosages in a 3+3 design with three pre-defined dose levels.
Detailed description
Immunotherapeutic approaches have emerged as an effective therapeutic approach in cancer. We will investigate the cell-surface ganglioside GD2 as a target since it is expressed on the cell surface of Ewing Sarcoma cells and clinical trials support the safety and efficacy of anti-GD2 antibodies in pediatric solid cancers.
Dinutuximab beta is a chimeric antibody that targets the disialoganglioside GD2. GD2 is expressed on a number of solid malignancies and was clinically investigated in pediatric patients with neuroblastoma. Expression in normal tissues is restricted to cerebellar neurons, skin melanocytes and peripheral pain fibers. Due to this expression pattern, anti-GD2 antibodies have been studied as targeted immunotherapy for neuroblastoma. With the results of these clinical trials, combination therapies with dinutuximab beta became a standard component of high-risk neuroblastoma therapy. GD2 expression is found in several EWS samples with variable expression-levels, and it is expected that anti-GD2 treatment is best suited as biomarker-driven approach.
The administration of vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide (VDC/IE) has been shown to be an effective systemic therapy and is therefore currently part of the standard treatment in Ewing Sarcoma. The international newest standard induction chemotherapy in the standard- and high-risk group consists of alternating VDC/IE. High-risk patients with a GD2 positive tumor could benefit from an addition of dinutuximab beta to the standard chemotherapy with VDC/IE.
The rationale for this trial is to investigate the feasibility, toxicity, and biological activity of dinutuximab beta in combination with standard chemotherapy in EWS.
This is a multi-center, phase 1, open-label, dose escalation study enrolling high-risk Ewing sarcoma patients that have been tested with GD2-positivity in a classical 3+3 design.
The decision to initiate treatment with 50% of the approved dosage for neuroblastoma in this dose-escalation study is grounded in both scientific literature and safety considerations. Starting at a lower dosage allows for the careful monitoring of patient response and minimizes the risk of adverse effects, particularly in a dose-sensitive adult population.
A risk assessment further supports this approach, indicating that starting at 50% of the approved neuroblastoma dose provides a safe baseline from which to escalate. The assessment outlines that a stepwise increase to 75% and subsequently to 100% of the approved dose allows for the identification of any dose-limiting toxicities (DLTs) in a controlled manner, thus optimizing patient safety.
The choice of 100 mg/m2 as the maximum dosage per cycle, equivalent to the dosage used in standard neuroblastoma treatment, is justified by its established efficacy and safety profile in this specific indication. The literature supports that doses up to 100 mg/m2 per cycle are well-tolerated in the majority of patients, with the therapeutic benefits outweighing the risks when administered within a carefully monitored clinical framework.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a multi-center, phase 1, open-label, dose escalation study enrolling high-risk Ewing sarcoma patients that have been tested with GD2-positivity in a classical 3+3 design.
| Arm | Type | Receives |
|---|---|---|
| dinutuximab beta added to standard chemotherapy | Experimental | Drug: Dinutuximab betaDinutuximab beta is added in different dosages to the standard chemotherapy |
Who may qualify
- Ages
- 12 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (22 listed)
- Histologically confirmed, newly diagnosed Ewing Sarcoma (m/f/d) or so-called Ewing-like sarcoma (i.e. translocation-positive small blue round cell sarcoma other than Rhabdomyosarcoma) of bone and / or soft tissue with evidence of EWS translocation by fluorescence in situ hybridization (FISH), real-time polymerase chain reaction (RT-PCR), or next-generation sequencing (NGS) assay
- High risk stratification (metastatic disease)
- Centrally confirmed GD2-positive tumor (biopsy of original and/or residual tumor or liquid biopsy in peripheral blood)
- Availability of fresh frozen tumor tissue for central GD2-detection
- Age ≥12 months
Key exclusion criteria (13 listed)
- Relapsed or refractory Disease state
- Patients with hypersensitivity against at least 1 component of the investigational medicinal product
- Significant illnesses and/or any of the following:
- Active and uncontrolled CNS metastases (indicated by clinical symptoms, cerebral edema, corticosteroid and/or anticonvulsant requirement, or progressive disease); for controlled CNS metastases, patient should have been off corticosteroids for at least 28 days without overt evidence of significant neurological deficits prior to enrollment
- Significant cardiac conduction abnormalities, including known familial prolonged QT syndrome, or screening QTc >480 msec
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 |
|---|---|---|
| Dinutuximab betaDinutuximab beta is added in different dosages to the standard chemotherapy | Drug | dinutuximab beta added to standard chemotherapy |
Primary outcome
GD2 Positivity
Time frame: after initial diagnosis and before study enrolment
local assessment for GD2 positivity
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 2 Nov 2026.
- Individual participant dataSharing planned: No
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.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dinutuximab beta in people with High-risk GD2 Positive Ewing Sarkoma, run by Prof. Dr. Dr. Birgit Burkhardt at 5 sites in Germany.
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 22 inclusion and 13 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 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Germany. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 Helena Kerp, PhD (+49 201 74 94 96 0, cess-gd2@gpoh-trials.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
GD2 Positivity (time frame: after initial diagnosis and before study enrolment). 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 2 Nov 2026.