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

Trial details

Who runs it

GPOH gGmbH

Trial code

EU 2024-515245-42-00

Record updated

2026. július 8.

Original description

The primary objective of this trial is to determine the recommended phase II dose (RP2D) of dinutuximab beta when administered in combination with vincristine, doxorubicin, and cyclophosphamide, as well as ifosfamide and etoposide, in patients with HR Ewing sarcoma. The trial will focus on dose-finding to identify the RP2D that maximizes therapeutic efficacy considering DLT.Read full original descriptionShow less

The primary objective of this trial is to determine the recommended phase II dose (RP2D) of dinutuximab beta when administered in combination with vincristine, doxorubicin, and cyclophosphamide, as well as ifosfamide and etoposide, in patients with HR Ewing sarcoma. The trial will focus on dose-finding to identify the RP2D that maximizes therapeutic efficacy considering DLT.

Inclusion: 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; 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); Wash-out phase with a minimum of 14 days after the last 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 renal function: creatinine clearance or glomerular filtration rate (GFR) > 60 mL/min/1.73 m2; 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%; 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; High risk stratification (metastatic disease); Centrally confirmed GD2-positive tumor (biopsy of original and/or residual tumor or liquid biopsy in peripheral blood).

Exclusion: 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; Relapsed or refractory disease state; Patients with hypersensitivity against at least one 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; clinically significant, symptomatic fluid in a third space; 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; 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; Significant cardiac conduction abnormalities, including known familial prolonged QT syndrome, or screening QTc >480 msec; Chronic Grade ≥2 diarrhea.

EU CTIS 2024-515245-42-00