Neuroblastoma (NBL)Phase 1GD2CART-BEVNCT07897968
GD2IL18CART Combined With Bevacizumab for Relapsed and Refractory GD2-positive Solid Tumors
A Phase 1 study testing Chimeric Antigen Receptor (CAR) Therapy Infusion and Bevacizumab (Avastin) in people with Neuroblastoma (NBL) and Ewing Sarcoma, run by Universität Münster at 1 site in Germany.
Trial summary
This study will test a chimeric antigen receptor (CAR) T-cell treatment combined with bevacizumab in children and young adults with relapsed or refractory neuroblastoma, Ewing sarcoma, or osteosarcoma. The CAR T-cell treatment, called GD2IL18CART, is made from a patient's own T cells. Read more about this study
- Who is it for?
- Ages 1 year to 25 years
- Conditions the study is for
- Neuroblastoma (NBL), Ewing Sarcoma, Osteosarcoma
- What is being tested?
- Chimeric Antigen Receptor (CAR) Therapy Infusion and Bevacizumab (Avastin)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteGermany
- Study dates
- 1 Oct 2027to 31 Dec 2032
- 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 1 year to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Participants must have relapsed and/or refractory neuroblastoma, osteosarcoma, or Ewing sarcoma judged to be incurable with conventional treatment and meet the following disease-specific requirements:
- Neuroblastoma: Patients with locoregional recurrence must have received surgery and/or radiotherapy followed by relapse chemotherapy. Patients with metastatic recurrence after initial classification as intermediate risk must have received high-risk therapy. Patients with recurrence after initial classification as high risk must have received relapse chemotherapy alone or combined with immunotherapy.
- Osteosarcoma: Patients must have received frontline therapy and at least one prior line of relapse systemic anticancer therapy for relapsed or refractory disease. Patients with an isolated relapse manifestation (lung metastasis or local relapse) must have unresectable disease.
- Ewing sarcoma: Patients must have received frontline therapy and at least one prior line of relapse chemotherapy according to standard regimens. Patients with an isolated lung relapse must have received pulmonary irradiation during frontline or relapse therapy.
- All participants must additionally meet the following criteria:
- GD2 expression on tumor cells in an archival biopsy assessed by the central reference laboratory. GD2-positive tumor is defined as GD2 at least 50% of tumor cells expressing GD2 at an intensity of 2+ or higher, using an immunofluorescence assay for specific detection of GD2 expression in formalin-fixed, paraffin-embedded or frozen tumor tissue with semiquantitative evaluation.
Show all 12Show fewer
- Evaluable disease based on Response Evaluation Criteria in Solid Tumors for all disease entities or, in cases of diffuse bone/bone marrow metastases, by whole-body nuclear medicine imaging (e.g. metaiodobenzylguanidine (MIBG)) scan for neuroblastoma or positron emission tomography (PET) based imaging.
- Age ≥1 year and ≤25 years.
- Absolute cluster of differentiation 3 (CD3)-positive T-cell count ≥200/µL.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2 for participants >16 years of age or Lansky performance score ≥60 for participants ≤16 years of age at screening.
- No childbearing potential, or negative pregnancy test at screening and before chemotherapy in participants with childbearing potential.
- Signed and dated informed consent/assent by participants and/or their caregivers before any trial-specific procedure.
Who cannot join
- Active solid central nervous system (CNS) metastases or metabolically active metastatic disease in the skull with direct contact to the dura.
- Current autoimmune disease or history of autoimmune disease with potential CNS involvement.
- Active clinically significant CNS dysfunction, including but not limited to uncontrolled seizure disorders, cerebrovascular ischemia or hemorrhage, dementia, or paralysis.
- History of an additional malignancy other than non-melanoma skin cancer or carcinoma in situ unless disease-free for ≥3 years.
- Pre-existing severe lung disease, oxygen requirement of >28% inspired oxygen (O2) supplementation, or active pulmonary infiltrates on X-ray.
- Cardiac function: Pediatric patients (˂18 yrs): fractional shortening <28% or left ventricular ejection fraction <50% by echocardiography, young adult patients (18-25 yrs): left ventricular ejection fraction <50% by echocardiography.
Show all 39Show fewer
- Renal function: GFR ≤29 mL/min/1.73 m22 by CKD-EPI for patients ≥18 yrs or creatinine clearance ≤29 mL/min/1.73 m2 by Schwartz formula for patients <18 yrs of age.
- Liver function: serum bilirubin >3 times the upper limit of normal (ULN) or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5 times ULN, unless attributable to liver infiltration by the underlying malignant disease.
- Hematological function: absolute neutrophil count (ANC) <500/µL or platelet count <50 × 10³/µL.
- Presence of any active infection.
- Bevacizumab-specific exclusion criteria:
- uncontrolled arterial hypertension, history of hypertensive crisis or hypertensive encephalopathy,
- clinically significant proteinuria.
- history of gastrointestinal perforation or clinically significant fistula, or current condition considered to confer a clinically relevant increased risk of gastrointestinal perforation,
- clinically significant bleeding or coagulopathy, including recent clinically significant hemoptysis or pulmonary hemorrhage,
- any history of clinically significant arterial thromboembolic event, including myocardial infarction, cerebrovascular accident, transient ischemic attack, or arterial thrombosis/embolism,
- clinically significant venous thromboembolism within 6 months before the first dose of bevacizumab,
- history of posterior reversible encephalopathy syndrome (PRES),
- clinically significant cardiovascular disease beyond inadequate left ventricular ejection fraction, e.g., uncontrolled arrhythmia, congestive heart failure, unstable angina.
- Rapidly progressive disease that in the estimation of the Investigator would compromise ability to complete study therapy.
- Pregnant or breast-feeding females.
- Concurrent or recent prior therapies:
- High-dose chemotherapy with autologous stem cell transplantation or requiring autologous stem cell rescue or anticancer biologicals (e.g. mifamurtide) or radiation therapy or major surgery within 30 days prior to leukapheresis.
- CAR T cells within 3 months before leukapheresis.
- Checkpoint inhibitors within less than 2 half lives prior to apheresis.
- Neuroblastoma patients who have relapsed after allogeneic or haploidentical stem cell transplantation must be at least 100 days posttransplant, with no evidence of GVHD and not taking immunosuppressive agents for at least 30 days prior to leukapheresis.
- I-131 MIBG therapy (neuroblastoma) or other targeted radionuclide therapy must be completed at least 3 months prior to apheresis.
- GD2-specific antibody therapy with dinutuximab beta or naxitamab within 40 days (5 half-lives) before apheresis.
- Antiproliferative chemotherapy, epigenetic agents, antibody-drug conjugates, or antibodies targeting antigens other than GD2 within 3 weeks prior apheresis.
- Immunosuppressive agents other than steroids within 2 weeks before apheresis.
- Short-acting molecularly targeted agents (kinase inhibitors) within 7 days before apheresis.
- Systemic corticosteroids, except physiologic replacement dosing, within 7 days before apheresis.
- Live vaccines within 30 days before apheresis.
- Hypersensitivity against any drug or its ingredients/impurities that is scheduled or likely to be given during trial participation, e.g. as part of the mandatory preparative chemotherapy, pre-medication for infusion, rescue medication/salvage therapies for treatment related toxicities.
- Contraindication to trial related procedures as judged by the Investigator, e.g., tumor biopsy.
- Female patients of child-bearing potential not willing to practice a highly effective form of birth control from the time of signing the informed consent form and for 12 months after dosing the IMP.
- Male patients of fathering potential not willing to practice a highly effective form of birth control from the time of signing the informed consent form and for 12 months after dosing the IMP.
- Concurrent participation in another interventional trial that could interact with this trial, e.g. CAR T trials.
- Cerebral dysfunction, legal incapacity of adult patients; Committal to an institution on judicial or official order.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Germany1 site
Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster
Münster, North Rhine-Westphalia, 48149
About this study
Official title: A Phase Ib Safety, Dose Finding and Feasibility Trial of GD2IL18CART Combined With Bevacizumab in Patients With Relapsed or Refractory GD2 Positive Solid Cancers
This study will test a chimeric antigen receptor (CAR) T-cell treatment combined with bevacizumab in children and young adults with relapsed or refractory neuroblastoma, Ewing sarcoma, or osteosarcoma.
The CAR T-cell treatment, called GD2IL18CART, is made from a patient's own T cells. The T cells are genetically modified to recognize GD2, a molecule found on the surface of these cancers, and to release the immune-stimulating protein interleukin-18 (IL-18) when they encounter tumor cells. Bevacizumab is an antibody that blocks vascular endothelial growth factor (VEGF), a protein that affects tumor blood vessels and may make it difficult for immune cells to enter tumors. Combining bevacizumab with GD2IL18CART may therefore help more CAR T cells reach the tumor and improve their antitumor activity.
The main goals of this study are to determine whether the combination can be given safely, identify a recommended dose of GD2IL18CART for use with bevacizumab, and look for early evidence of antitumor activity. The study will also examine blood and tumor samples to better understand how the treatment affects CAR T cells and the tumor environment.
Read the detailed description
This is an international, prospective, multicenter, open-label, non-randomized phase Ib dose-escalation and dose-expansion study evaluating GD2IL18CART in combination with bevacizumab in children, adolescents, and young adults with relapsed or refractory GD2-positive neuroblastoma, Ewing sarcoma, or osteosarcoma.
GD2IL18CART is an autologous chimeric antigen receptor (CAR) T-cell product directed against the tumor-associated antigen GD2 and engineered for antigen-inducible secretion of interleukin-18 (IL-18). Clinical investigation of GD2IL18CART as a single agent demonstrated robust CAR T-cell expansion and established doses that could be administered with a manageable safety profile. However, clinical activity remained limited, particularly at non-osseous tumor sites and in Ewing sarcoma and osteosarcoma.
The combination with bevacizumab is intended to address tumor microenvironmental barriers that may limit CAR T-cell access and activity. Bevacizumab is a monoclonal antibody that neutralizes vascular endothelial growth factor A (VEGF-A). Persistent VEGF signaling contributes to abnormal tumor vasculature that can restrict immune-cell trafficking and promote local immunosuppression. In preclinical models of Ewing sarcoma and neuroblastoma, vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR) pathway inhibition increased intratumoral accumulation and antitumor activity of GD2-directed CAR T cells. Bevacizumab also enhanced the antitumor activity of the clinical GD2IL18CART product. These findings provide the rationale for evaluating the combination clinically.
Following leukapheresis and manufacture of the autologous GD2IL18CART product, participants will receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide on days -6 to -4. Bevacizumab will be administered intravenously at 15 mg/kg on day -3, followed by a single intravenous infusion of GD2IL18CART on day 0. Additional bevacizumab doses will be administered every 3 weeks for up to five doses in total, unless treatment is discontinued earlier according to protocol-defined criteria. The timing of bevacizumab is intended to initiate VEGF inhibition before CAR T-cell infusion and maintain VEGF inhibition during the early period of CAR T-cell trafficking, expansion, and persistence.
GD2IL18CART dose escalation will follow a cohort-based single ascending dose design. The starting dose is lower than the doses established during previous clinical investigation of GD2IL18CART as a single agent because bevacizumab may increase tumor infiltration and biological activity of the CAR T cells. Cohorts of three participants will be treated sequentially, with predefined stopping rules and independent Data Monitoring Committee review guiding dose escalation. The objective of the dose-escalation phase is to characterize the safety of the combination and determine a recommended GD2IL18CART dose for use with bevacizumab.
After determination of the recommended combination dose, disease-specific expansion cohorts will enroll participants with neuroblastoma, Ewing sarcoma, and osteosarcoma, with up to six participants per disease entity treated at the recommended dose. The expansion phase will further characterize safety, feasibility, biological activity, and preliminary antitumor activity of the combination.
Tumor response will be assessed at weeks 6 and 12 and at months 6 and 12. Participants will be followed within this study through month 12. Long-term follow-up after genetically modified cell therapy will continue for up to 15 years in a separate long-term follow-up study.
An integrated translational research program will investigate the biological effects of the combination. Longitudinal analysis of blood samples will assess CAR T-cell expansion, persistence, phenotype, and immune responses. Mandatory on-treatment tumor biopsies obtained on day 14 will be analyzed using molecular and spatial approaches to investigate CAR T-cell trafficking and function within the tumor microenvironment and to identify potential biological determinants of response and resistance.
- Conditions
- Neuroblastoma (NBL), Ewing Sarcoma, Osteosarcoma
- Being tested
- Chimeric Antigen Receptor (CAR) Therapy Infusion, Bevacizumab (Avastin)
- Keywords
- CAR T-cell therapy, GD2, GD2IL18CART, IL-18, VEGF, VEGF inhibition, pediatric solid tumors, neuroblastoma, osteosarcoma, Ewing sarcoma, bevacizumab
- Medical subject headings
- Neuroblastoma, Sarcoma, Ewing, Osteosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chimeric Antigen Receptor (CAR) Therapy InfusionGenetic
Also called GD2IL18CART
Combination of GD2IL1CART (IMP1, EU CT 2022-501725-21-00) with a monoclonal antibody against vascular endothelial growth factor, bevacizumab (IMP2) to promote effective CAR T-cell accumulation and function within the immunosuppressive tumor microenvironment (TME).
Bevacizumab (Avastin)Drug
In combination with GD2IL18CART (IMP1, EU CT 2022-501725-21-00)
| Study group | Role | What they receive |
|---|---|---|
| GD2IL18CART + bevacizumab | Experimental | Participants receive a single intravenous infusion of freshly prepared autologous GD2IL18CART cells in combination with intravenous bevacizumab administered every 3 weeks for up to 5 doses. Receives: Genetic: Chimeric Antigen Receptor (CAR) Therapy Infusion; Drug: Bevacizumab (Avastin) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of adverse events
Incidence and severity of adverse events (AEs), graded according to CTCAE version 6.0
Measured: Through 12 months after GD2IL18CART infusion
Dose-limiting toxicities and recommended dose - dose-finding part
Incidence of protocol-defined dose-limiting toxicities (DLTs) and determination of the recommended dose (RD) of GD2IL18CART in combination with bevacizumab using a rule-based small-cohort design
Measured: 28 days after IMP infusion
Recommended dose of GD2IL18CART in combination with bevacizumab
Determination of the recommended dose (RD) of GD2IL18CART in combination with bevacizumab using a rule-based small-cohort dose-escalation design, based on observed dose-limiting toxicities (DLTs) and protocol-defined dose-escalation and stopping rules.
Measured: Through completion of the protocol-defined DLT assessment period of 28 days for the final dose-finding cohort
Overall response rate at week 6 - dose-extension part
Proportion of participants achieving a complete response (CR) or partial response (PR) at week 6
Measured: Week 6
Secondary outcomes (2)
Intratumoral infiltration of GD2IL18CART
Presence and extent of GD2IL18CART-cell infiltration in on-treatment tumor biopsies
Measured: Day 14
Expansion and persistence of GD2IL18CART
Longitudinal assessment of GD2IL18CART-cell expansion, persistence and phenotype in peripheral blood
Measured: From GD2IL18CART infusion through 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2026
- Study start1 Oct 2027 (estimated)
- Primary completion30 Sep 2031 (estimated)
- Study completion31 Dec 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neuroblastoma (NBL)Studies 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
- Sequential
- Model description
- Sequential single ascending dose (SAD) design with subsequent dose expansion. Cohorts of 3 participants will be evaluated sequentially for dose-limiting toxicities, with prospectively defined stopping rules and independent Data Monitoring Committee review guiding dose escalation. After determination of the recommended combination dose, disease-specific expansion cohorts will be enrolled.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universität Münster
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital Erlangen, Princess Maxima Center for Pediatric Oncology, St. Anna Children's Hospital, Vienna, University Hospital Tuebingen, Oslo University Hospital
- Responsible party
- Sponsor
- Investigators
- Claudia Rossig, MD, Principal investigator, University Children´s Hospital Münster
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07897968
- Sponsor's protocol ID
- UniMS26_026
- Acronym
- GD2CART-BEV
- Status last verified
- Oct 2026
- First submitted
- 20 Oct 2026
- Last updated
- 3 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data underlying the published results may be made available to qualified researchers upon reasonable request following publication, subject to applicable informed consent, ethical and data-protection requirements, and execution of an appropriate data-use agreement.
Publications
Fischer-Riepe L, Kailayangiri S, Zimmermann K, Pfeifer R, Aigner M, Altvater B, Kretschmann S, Volkl S, Hartley J, Dreger C, Petry K, Bosio A, von Dollen A, Hartmann W, Lode H, Gorlich D, Mackensen A, Jungblut M, Schambach A, Abken H, Rossig C. Preclinical Development of CAR T Cells with Antigen-Inducible IL18 Enforcement to Treat GD2-Positive Solid Cancers. Clin Cancer Res. 2024 Aug 15;30(16):3564-3577. doi: 10.1158/1078-0432.CCR-23-3157.
PubMed 38593230
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Safety, Dose Finding and Feasibility Trial of GD2IL18CART Combined With Bevacizumab in Patients With Relapsed or Refractory GD2 Positive Solid Cancers
- ClinicalTrials.gov ID
- NCT07897968
- Acronym / sponsor ID
- GD2CART-BEV / UniMS26_026
- Conditions
- Neuroblastoma (NBL), Ewing Sarcoma, Osteosarcoma
- Keywords
- CAR T-cell therapy, GD2, GD2IL18CART, IL-18, VEGF, VEGF inhibition, pediatric solid tumors, neuroblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Universität MünsterUniversity, hospital or other
- Collaborators
- University Hospital Erlangen, Princess Maxima Center for Pediatric Oncology, St. Anna Children's Hospital, Vienna, University Hospital Tuebingen, Oslo University Hospital
- Study start
- 1 Oct 2027 (estimated)
- Primary completion
- 30 Sep 2031 (estimated)
- Study completion
- 31 Dec 2032 (estimated)
- First posted
- 27 Oct 2026 (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.
This study will test a chimeric antigen receptor (CAR) T-cell treatment combined with bevacizumab in children and young adults with relapsed or refractory neuroblastoma, Ewing sarcoma, or osteosarcoma.
The CAR T-cell treatment, called GD2IL18CART, is made from a patient's own T cells. The T cells are genetically modified to recognize GD2, a molecule found on the surface of these cancers, and to release the immune-stimulating protein interleukin-18 (IL-18) when they encounter tumor cells. Bevacizumab is an antibody that blocks vascular endothelial growth factor (VEGF), a protein that affects tumor blood vessels and may make it difficult for immune cells to enter tumors. Combining bevacizumab with GD2IL18CART may therefore help more CAR T cells reach the tumor and improve their antitumor activity.
The main goals of this study are to determine whether the combination can be given safely, identify a recommended dose of GD2IL18CART for use with bevacizumab, and look for early evidence of antitumor activity. The study will also examine blood and tumor samples to better understand how the treatment affects CAR T cells and the tumor environment.
Detailed description
This is an international, prospective, multicenter, open-label, non-randomized phase Ib dose-escalation and dose-expansion study evaluating GD2IL18CART in combination with bevacizumab in children, adolescents, and young adults with relapsed or refractory GD2-positive neuroblastoma, Ewing sarcoma, or osteosarcoma.
GD2IL18CART is an autologous chimeric antigen receptor (CAR) T-cell product directed against the tumor-associated antigen GD2 and engineered for antigen-inducible secretion of interleukin-18 (IL-18). Clinical investigation of GD2IL18CART as a single agent demonstrated robust CAR T-cell expansion and established doses that could be administered with a manageable safety profile. However, clinical activity remained limited, particularly at non-osseous tumor sites and in Ewing sarcoma and osteosarcoma.
The combination with bevacizumab is intended to address tumor microenvironmental barriers that may limit CAR T-cell access and activity. Bevacizumab is a monoclonal antibody that neutralizes vascular endothelial growth factor A (VEGF-A). Persistent VEGF signaling contributes to abnormal tumor vasculature that can restrict immune-cell trafficking and promote local immunosuppression. In preclinical models of Ewing sarcoma and neuroblastoma, vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR) pathway inhibition increased intratumoral accumulation and antitumor activity of GD2-directed CAR T cells. Bevacizumab also enhanced the antitumor activity of the clinical GD2IL18CART product. These findings provide the rationale for evaluating the combination clinically.
Following leukapheresis and manufacture of the autologous GD2IL18CART product, participants will receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide on days -6 to -4. Bevacizumab will be administered intravenously at 15 mg/kg on day -3, followed by a single intravenous infusion of GD2IL18CART on day 0. Additional bevacizumab doses will be administered every 3 weeks for up to five doses in total, unless treatment is discontinued earlier according to protocol-defined criteria. The timing of bevacizumab is intended to initiate VEGF inhibition before CAR T-cell infusion and maintain VEGF inhibition during the early period of CAR T-cell trafficking, expansion, and persistence.
GD2IL18CART dose escalation will follow a cohort-based single ascending dose design. The starting dose is lower than the doses established during previous clinical investigation of GD2IL18CART as a single agent because bevacizumab may increase tumor infiltration and biological activity of the CAR T cells. Cohorts of three participants will be treated sequentially, with predefined stopping rules and independent Data Monitoring Committee review guiding dose escalation. The objective of the dose-escalation phase is to characterize the safety of the combination and determine a recommended GD2IL18CART dose for use with bevacizumab.
After determination of the recommended combination dose, disease-specific expansion cohorts will enroll participants with neuroblastoma, Ewing sarcoma, and osteosarcoma, with up to six participants per disease entity treated at the recommended dose. The expansion phase will further characterize safety, feasibility, biological activity, and preliminary antitumor activity of the combination.
Tumor response will be assessed at weeks 6 and 12 and at months 6 and 12. Participants will be followed within this study through month 12. Long-term follow-up after genetically modified cell therapy will continue for up to 15 years in a separate long-term follow-up study.
An integrated translational research program will investigate the biological effects of the combination. Longitudinal analysis of blood samples will assess CAR T-cell expansion, persistence, phenotype, and immune responses. Mandatory on-treatment tumor biopsies obtained on day 14 will be analyzed using molecular and spatial approaches to investigate CAR T-cell trafficking and function within the tumor microenvironment and to identify potential biological determinants of response and resistance.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Sequential single ascending dose (SAD) design with subsequent dose expansion. Cohorts of 3 participants will be evaluated sequentially for dose-limiting toxicities, with prospectively defined stopping rules and independent Data Monitoring Committee review guiding dose escalation. After determination of the recommended combination dose, disease-specific expansion cohorts will be enrolled.
| Arm | Type | Receives |
|---|---|---|
| GD2IL18CART + bevacizumab | Experimental | Genetic: Chimeric Antigen Receptor (CAR) Therapy Infusion, Drug: Bevacizumab (Avastin)Participants receive a single intravenous infusion of freshly prepared autologous GD2IL18CART cells in combination with intravenous bevacizumab administered every 3 weeks for up to 5 doses. |
Who may qualify
- Ages
- 1 year to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (12 listed)
- Participants must have relapsed and/or refractory neuroblastoma, osteosarcoma, or Ewing sarcoma judged to be incurable with conventional treatment and meet the following disease-specific requirements:
- All participants must additionally meet the following criteria:
Key exclusion criteria (39 listed)
- Active solid central nervous system (CNS) metastases or metabolically active metastatic disease in the skull with direct contact to the dura.
- Current autoimmune disease or history of autoimmune disease with potential CNS involvement.
- Active clinically significant CNS dysfunction, including but not limited to uncontrolled seizure disorders, cerebrovascular ischemia or hemorrhage, dementia, or paralysis.
- History of an additional malignancy other than non-melanoma skin cancer or carcinoma in situ unless disease-free for ≥3 years.
- Pre-existing severe lung disease, oxygen requirement of >28% inspired oxygen (O2) supplementation, or active pulmonary infiltrates on X-ray.
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 |
|---|---|---|
| Chimeric Antigen Receptor (CAR) Therapy InfusionAlso: GD2IL18CARTCombination of GD2IL1CART (IMP1, EU CT 2022-501725-21-00) with a monoclonal antibody against vascular endothelial growth factor, bevacizumab (IMP2) to promote effective CAR T-cell accumulation and function within the immunosuppressive tumor microenvironment (TME). | Genetic | GD2IL18CART + bevacizumab |
| Bevacizumab (Avastin)In combination with GD2IL18CART (IMP1, EU CT 2022-501725-21-00) | Drug | GD2IL18CART + bevacizumab |
Primary outcome
Incidence and severity of adverse events
Time frame: Through 12 months after GD2IL18CART infusion
Incidence and severity of adverse events (AEs), graded according to CTCAE version 6.0
Dose-limiting toxicities and recommended dose - dose-finding part
Time frame: 28 days after IMP infusion
Incidence of protocol-defined dose-limiting toxicities (DLTs) and determination of the recommended dose (RD) of GD2IL18CART in combination with bevacizumab using a rule-based small-cohort design
Recommended dose of GD2IL18CART in combination with bevacizumab
Time frame: Through completion of the protocol-defined DLT assessment period of 28 days for the final dose-finding cohort
Determination of the recommended dose (RD) of GD2IL18CART in combination with bevacizumab using a rule-based small-cohort dose-escalation design, based on observed dose-limiting toxicities (DLTs) and protocol-defined dose-escalation and stopping rules.
Overall response rate at week 6 - dose-extension part
Time frame: Week 6
Proportion of participants achieving a complete response (CR) or partial response (PR) at week 6
2 secondary outcomes
Intratumoral infiltration of GD2IL18CART
Time frame: Day 14
Expansion and persistence of GD2IL18CART
Time frame: From GD2IL18CART infusion through 12 months
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 3 Nov 2026.
- Background: PubMed 38593230Fischer-Riepe L, Kailayangiri S, Zimmermann K, Pfeifer R, Aigner M, Altvater B, Kretschmann S, Volkl S, Hartley J, Dreger C, Petry K, Bosio A, von Dollen A, Hartmann W, Lode H, Gorlich D, Mackensen A, Jungblut M, Schambach A, Abken H, Rossig C. Preclinical Development of CAR T Cells with Antigen-Inducible IL18 Enforcement to Treat GD2-Positive Solid Cancers. Clin Cancer Res. 2024 Aug 15;30(16):3564-3577. doi: 10.1158/1078-0432.CCR-23-3157.
- Individual participant dataSharing planned: Yes. De-identified individual participant data underlying the published results may be made available to qualified researchers upon reasonable request following publication, subject to applicable informed consent, ethical and data-protection requirements, and execution of an appropriate data-use agreement.
Related trials for Neuroblastoma (NBL)
RecruitingPhase 1/2
SPEARHEAD-3 Pediatric Study
Synovial Sarcoma, Malignant Peripheral Nerve Sheath Tumor (MPNST)
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.
Claudia Rossig, MD principal investigator
University Children´s Hospital Münster
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Chimeric Antigen Receptor (CAR) Therapy Infusion and Bevacizumab (Avastin) in people with Neuroblastoma (NBL) and Ewing Sarcoma, run by Universität Münster at 1 site 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 12 inclusion and 39 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: opening soon, as of the sponsor's last update on 3 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 1 site 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 Claudia Rossig, MD (00492518347742, rossig@ukmuenster.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and severity of adverse events (time frame: Through 12 months after GD2IL18CART infusion). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07897968, which also lists 1 linked publication.
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 3 Nov 2026; AzTrials last refreshed its copy on 8 Nov 2026.