Study to find out whether adding the medicine Naxitamab to standard treatment could help children and teenagers who have just been diagnosed with high-risk neuroblastoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacio Sant Joan De Deu

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-05-19

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Beat Childhood Cancer Foundation

External identifiers

EU CT number

2025-524140-35-00

ClinicalTrials.gov

NCT05489887

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the Complete Response (CR) rate at end-of-induction (EOI) per the 1993 International Neuroblastoma Response Criteria (INRC) in newly diagnosed subjects with high-risk neuroblastoma treated with naxitamab + Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) + standard induction therapy, compared against a historical control rate.

Secondary objectives 6

1. 1993 INRC CR/VGPR & ORR: Evaluate the combined CR + Very Good Partial Response (VGPR) rate and objective response rate (ORR; CR + VGPR + PR) at EOI per 1993 INRC, compared against historical controls and external controls.
2. 2017 INRC CR & ORR: Evaluate CR rate and ORR (CR + PR) at EOI per the 2017 INRC, compared against external controls.
3. Survival: Compare event-free survival (EFS), progression-free survival (PFS), and overall survival (OS) to external controls.
4. Other Metrics: Assess metastatic CR, changes in soft-tissue lesions and bone marrow infiltration, Curie Score, and minimal residual disease (MRD) status at predefined time points during induction and at EOI, and compare to external controls.
5. Safety/Tolerability: Characterise the incidence and severity of adverse events with naxitamab + GM-CSF + standard induction therapy.
6. PK/Immunogenicity: Describe the pharmacokinetic profile of naxitamab and assess immunogenicity in combination with GM-CSF and chemotherapy.

Conditions and MedDRA coding

Neuroblastoma or ganglioneuroblastoma (nodular or intermixed)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Diagnosis: Subjects must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular or intermixed) verified by histology or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites. Subjects with the following disease stages at diagnosis are eligible, if they meet the other specified criteria[1]:Subjects with newly diagnosed neuroblastoma with INRGSS Stage M disease with either of the following features: a) MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features; OR b) 365 days to ≤ 547 days of age without MYCN amplification, but unfavorable biologic features such as unfavorable histology (INPC) or diploid tumor (DNA index=1) or the presence of any segmental chromosome aberration (SCA) (somatic copy number loss at 1p, 3p, 4p, or 11q or somatic copy number gain at 1q, 2p, or 17q); OR c) Age > 547 days of age regardless of biologic features Subjects with newly diagnosed neuroblastoma with INRGSS Stage MS disease with either of the following: a) MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals); OR b) 365 days to ≤ 547 days (18 months) of age without MYCN amplification, but unfavorable biologic features such as unfavorable histology (INPC) or diploid tumor (DNA index=1) or SCA as above Subjects with newly diagnosed neuroblastoma INRGSS Stage L2 disease with either of the following: a) MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals); OR b) 18 months to <5 years of age without MYCN amplification, but with unfavorable histology (INPC); OR c) ≥5 years of age without MYCN amplification, but with undifferentiated or poorly differentiated INPC Subjects with newly diagnosed neuroblastoma INRGSS Stage L1 disease that is incompletely resected with MYCN amplification. Subjects > 547 days of age initially diagnosed with INRGSS Stage L1, L2 or MS disease who progressed to Stage M without prior chemotherapy may enroll within 4 weeks of progression to Stage M. Subjects ≥ 365 days of age initially diagnosed with MYCN amplified INRGSS Stage L1 disease who progress to Stage M without systemic therapy may enroll within 4 weeks of progression to Stage M.
2. Subjects must be age ≤ 21 years at initial diagnosis.
3. Subjects must be >12 months of age at enrolment.
4. Adequate cardiac function defined as: a. Shortening fraction of ≥ 27% by echocardiogram, or b. Ejection fraction of ≥ 50% by radionuclide evaluation or echocardiogram.
5. Adequate liver function must be demonstrated, defined as: a. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age AND b. ALT (SGPT) < 5 x upper limit of normal (ULN) for age
6. Subjects must have adequate renal function defined as:  For subjects < 17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Bedside Schwartz equation (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Bedside Schwartz equation is: [(0.413) X (Height in cm)] / SCr  For subjects ≥17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Cockcroft and Gault formula (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Cockcroft and Gault formula is: [(140- age) x (Wt in kg) x (0.85 if female)] / (72 x SCr).  OR a 24 hour urine Creatinine clearance ≥ 70 mL/min/1.73 m2
7. A negative serum pregnancy test is required for female participants of childbearing potential (≥13 years of age or after onset of menses).
8. Both male and female post-pubertal study subjects must be willing to use a highly effective contraceptive method (i.e., achieves a failure rate of <1% per year when used consistently and correctly) from the time of informed consent (and assent, as applicable) until 6 months after study treatment discontinuation. Such methods include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner, sexual abstinence.onset of menses).
9. Informed Consent: All subjects and/or legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines and applicable local regulations.

Exclusion criteria 9

1. Subjects who are less than 1 year of age
2. Subjects who are 12-18 months of age with INRGSS Stage M and all stage L2 subjects with favorable biologic features (i.e., nonamplified MYCN, favorable pathology, and DNA index > 1) are not eligible.
3. Subjects who have had prior systemic therapy except for localized emergency radiation to sites of life-threatening or function-threatening disease and/or no more than 1 cycle of chemotherapy.
4. Treatment with immunosuppressive treatment (topical, inhaled and short-term emergency steroids excluded) within 4 weeks prior to enrolment.
5. Inadequate pulmonary function defined as evidence of dyspnea at rest, exercise intolerance, and/or chronic oxygen requirement. In addition, room air pulse oximetry < 94% and/or abnormal pulmonary function tests if these assessments are clinically indicated.
6. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study.)
7. Subjects receiving any investigational drug concurrently.
8. Subjects with any other medical condition, including but not limited to malabsorption syndromes, mental illness or substance abuse, deemed by the Investigator to be likely to interfere with the interpretation of the results or which would interfere with a subject’s ability to sign or the legal guardian’s ability to sign the informed consent, and subject’s ability to cooperate and participate in the study.
9. Subjects with a significant intercurrent illness (any ongoing serious medical problem unrelated to cancer or its treatment) that is not covered by the detailed exclusion criteria and that is expected to interfere with the action of investigational medicinal products (IMPs) or to significantly increase the severity of the toxicities experienced from trial treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Rate of complete response (CR) at end-of-induction (EOI) per 1993 INRC as assessed by a Blinded Independent Central Review (BICR).

Secondary endpoints 24

1. Rate of combined CR + VGPR at EOI per 1993 INRC as assessed by BICR Committee.
2. Objective Response Rate (ORR; CR + VGPR + PR) at EOI per 1993 INRC by BICR Committee.
3. Rate of CR at EOI per the 2017 INRC by BICR Committee.
4. ORR (CR + PR) at EOI per 2017 INRC by BICR Committee.
5. Event-free survival (EFS), defined as time from first study treatment to first event (relapse, progression, secondary malignancy, or death) or last contact.
6. Progression-free survival (PFS), defined as time from first study treatment to documented progression or death, or censored at last contact.
7. Overall survival (OS), defined as time from first study treatment to death, or censored at last contact.
8. Metastatic CR rate (bone, soft tissue, and/or bone marrow) per 2017 INRC by BICR Committee at the following stages: (i) After cycle 2, (ii) After cycle 4, (iii) at EOI.
9. Overall response category (CR, PR, MR, SD, or PD) per 2017 INRC by BICR at the following stages: (i) After cycle 2, (ii) After cycle 4, (iii) at EOI.
10. Achievement of CR at EOI and confirmation at end of consolidation per 2017 INRC by BICR Committee.
11. Percent change in sum of diameters of soft-tissue lesions from baseline to EOI per 2017 INRC by BICR Committee.
12. Percent change in primary tumor volume from baseline to each induction assessment and EOI per 2017 by BICR Committee.
13. Change in bone-marrow infiltration category from baseline to each induction assessment and EOI per 2017 INRC by BICR Committee.
14. Change in Curie Score—overall and bone-only—from baseline to each induction assessment and EOI, and maximum change to EOI per 2017 INRC by BICR Committee.
15. Conversion from detectable disease to MRD-negative in bone marrow at end of treatment by RT-qPCR (i.e. depth of response).
16. Investigator-assessed versions of all of the above.
17. Proportion of samples for independent review needing adjudication due to discrepancy in review outcome.
18. Incidence, severity, and relationship of adverse events (AEs) and serious adverse events (SAEs).
19. Incidence and duration of grade ≥3 AEs related to naxitamab.
20. Proportion of patients with infusion-related pain by Wong-Baker and FLACC scales.
21. AEs leading to dose delay, dose reduction, or discontinuation of naxitamab.
22. Naxitamab related AEs preventing/delaying patients in moving on to consolidation.
23. Naxitamab PK parameters (C_max, AUC, clearance, volume of distribution, half-life).
24. Incidence and titers of anti-drug antibodies.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacio Sant Joan De Deu

Sponsor organisation

Fundacio Sant Joan De Deu

Address

Calle Santa Rosa 39-57 3a Planta

City

Esplugues De Llobregat

Postcode

08950

Country

Spain

Scientific contact point

Organisation

Fundacio Sant Joan De Deu

Contact name

Jaume Mora Graupera

Public contact point

Organisation

Fundacio Sant Joan De Deu

Contact name

Clinical Trial Unit

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

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