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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

GPOH gGmbH

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

24 Apr 2025 → ongoing

Decision date (initial)

2025-02-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

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.

Secondary objectives 3

1. To assess the Progression-Free Survival (PFS) of patients treated with the combination of dinutuximab beta, vincristine, doxorubicin, and cyclophosphamide, as well as ifosfamide and etoposide.
2. To evaluate Event-Free Survival (EFS) in patients receiving the study treatment.
3. To determine the Duration of Response (DOR) in patients who achieve a partial or complete response to the study treatment.

Conditions and MedDRA coding

Ewing Sarcoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. 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
2. 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
3. Adequate cardiac function: confirmed by echocardiography with a left ventricular ejection fraction (LVEF) of ≥ 50%
4. No known active HIV, HBV, or HCV infection
5. No severe neurological impairment, particularly no motor or sensory deficits, except for neurological deficits caused by Ewing sarcoma
6. 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
7. Patient or their legal representative is willing and able to comply with the requirements of the study protocol
8. High risk stratification (metastatic disease)
9. Centrally confirmed GD2-positive tumor (biopsy of original and/or residual tumor or liquid biopsy in peripheral blood)
10. Availability of fresh frozen tumor tissue for central GD2-detection
11. Age ≥12 months
12. Start of first line treatment according to standard induction treatment (Cycle 1-4: VDC – IE – VDC – IE)
13. Wash-out phase with a minimum of 14 days after the last dose of the last chemotherapy
14. Lansky (<16 years) Performance Score ≥70% or ECOG (≥16 years) ≤ 2
15. 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
16. Adequate renal function: creatinine clearance or glomerular filtration rate (GFR) > 60 mL/min/1.73 m2

Exclusion criteria 9

1. Relapsed or refractory disease state
2. Patients with hypersensitivity against at least one component of the investigational medicinal product
3. 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
4. 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
5. Chronic Grade ≥2 diarrhea
6. Diagnosis of any malignancy other than the disease under study
7. 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
8. Significant cardiac conduction abnormalities, including known familial prolonged QT syndrome, or screening QTc >480 msec
9. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the identification of the recommended phase II dose (RP2D) of dinutuximab beta in combination with vincristine, doxorubicin, and cyclophosphamide, as well as ifosfamide and etoposide, based on the evaluation of dose-limiting toxicities (DLTs), overall safety, and tolerability within the study population.

Secondary endpoints 3

1. Progression-Free Survival (PFS): The time from the start of treatment until the first documented evidence of disease progression or death from any cause, whichever occurs first.
2. Event-Free Survival (EFS): The time from the initiation of treatment to the occurrence of any treatment-related event, including disease progression, relapse, occurrence of a second malignancy, or death from any cause.
3. Duration of Response (DOR): The time from the first documentation of a complete or partial response to the treatment until the first occurrence of disease progression or relapse.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

GPOH gGmbH

Sponsor organisation

GPOH gGmbH

Address

Holsterhauser Platz 2, Holsterhausen Holsterhausen

City

Essen

Postcode

45147

Country

Germany

Scientific contact point

Organisation

GPOH gGmbH

Contact name

Prof. Dr. med. Uta Dirksen

Public contact point

Organisation

GPOH gGmbH

Contact name

Prof. Dr. med. Dirk Reinhardt

Third parties 2

Locations

4 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

5 submissions — initial application plus substantial / non-substantial modifications