Phase 2/3 Study of hu14.18K322A Combined with Irinotecan and Temozolomide in Children with Relapsed or Refractory High‑Risk Neuroblastoma
- Trial ID
- 2025-524397-42-00
- Protocol
- EPG-HU1418-201
- Sponsor
- Renaissance Pharma Limited
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to determine the efficacy of hu14.18K322A administered intravenously in combination with standard chemotherapy in children and adolescents with high-risk neuroblastoma, including cohorts with disease relapse or refractory disease, to establish therapeutic benefit in this poor‑prognosis population. Secondary objectives are to assess the safety and tolerability of the regimen, to evaluate patient‑reported and observer‑reported outcome measures, to characterize the immunogenicity profile of hu14.18K322A, to explore the predictive value of selected biomarkers obtained from treatment‑related samples, and to define the pharmacokinetic parameters of the antibody when given with chemotherapy.
Participants
The trial enrolled 92 participants diagnosed with high‑risk neuroblastoma (HRNB) who were either relapsed after prior therapy or refractory to treatment. Eligible individuals were between 18 months and <18 years of age at enrollment, encompassing both males and females, and all were classified as vulnerable minors requiring parental consent. Inclusion required histologically confirmed metastatic HRNB, measurable disease per INRC criteria, and a Lansky or Karnofsky performance status of ≥50 %. Participants had to demonstrate adequate hematologic, renal, hepatic, cardiac, pulmonary, and central‑nervous‑system function according to predefined laboratory thresholds, and must have recovered from recent surgery or chemotherapy toxicity. Additional criteria specified a minimum interval since prior anti‑GD2 therapy, autologous stem‑cell transplant, or major surgical procedures, and mandated contraception use where applicable. The study population was selected on the basis of these clinical and laboratory parameters to ensure suitability for the combined hu14.18K322A and chemotherapy regimen.
Plans and Procedures
The study is an integrated Phase II/III therapeutic trial evaluating the efficacy, safety, and tolerability of hu14.18K322A administered in combination with temozolomide, irinotecan, and the anti‑GD2 monoclonal antibody Daretabart in participants with high-risk neuroblastoma. Participants are enrolled after a screening visit that confirms eligibility criteria, including age 18 months to <18 years, measurable disease per INRC, and adequate organ function. Following eligibility confirmation, participants receive the investigational regimen according to the protocol‑defined schedule, with subsequent study visits scheduled at regular intervals to assess treatment administration, clinical response, laboratory parameters, and adverse events. The visit schedule includes: • Screening visit (baseline assessments) • Treatment visits (infusions of Daretabart, irinotecan, and temozolomide) • Follow‑up visits (clinical and imaging evaluations) • End‑of‑study visit (final safety and efficacy assessments). The trial duration for each participant extends from the screening visit through the end‑of‑study visit, encompassing the entire treatment course and post‑treatment follow‑up. The primary efficacy assessment differs by sub‑protocol: Sub‑Protocol A uses the objective response rate (ORR) (proportion achieving complete or partial response per INRC), while Sub‑Protocol B employs the minimal complete response rate (mCRR) (proportion achieving overall minimal complete response). Secondary endpoints are detailed in the protocol. The overall study recruitment period is planned from July 2026 to July 2029.
Treatment
Temodal 5 mg hard capsules contain the active substance temozolomide. The pharmaceutical form is a hard capsule intended for preparation as a solution for infusion. The administered dose is 100 mg/m². The route of administration is infusion, and dosing follows the study‑specified schedule for each treatment cycle. Compliance is monitored by recording the administered dose and confirming capsule count at each visit.
Daretabart is a humanised IgG1 (K322A) monoclonal antibody directed against disialoganglioside GD2, designated hu14.18K322A. It is supplied as a solution for intravenous infusion. The dose is 60 mg/m² per infusion. Administration occurs according to the protocol‑defined infusion schedule, typically once per cycle. Infusion duration, pre‑medication, and vital sign monitoring are documented to ensure adherence.
IRINOTECAN is provided as a solution for infusion. The dose is 50 mg/m². Administration is by infusion according to the protocol‑defined timing within each chemotherapy cycle. Dose calculations, infusion start and stop times, and any dose modifications are recorded to support participant compliance monitoring.
Efficacy
Efficacy will be evaluated by determining the proportion of participants who achieve a complete response (CR) or partial response (PR) according to the International Neuroblastoma Response Criteria (INRC) in Sub‑Protocol A, expressed as the overall response rate (ORR). In Sub‑Protocol B, efficacy will be assessed by the proportion of participants attaining an overall metastatic complete response (mCR) (mCRR). These response assessments will be performed using standard imaging and clinical evaluation procedures defined in the protocol.
Additional secondary efficacy measures, as detailed in the protocol sections M.2, A2 and B2, will be analyzed in a comparable manner.
Inclusion and Exclusion Criteria
Inclusion Criteria
- ≥18 months to <18 years 2. Initially diagnosed with histologically proven HRNB with metastatic disease 3. Have evaluable or measurable disease per INRC, (Park, 2017) 4. Have a Lansky performance status of ≥50 or Karnofsky performance status ≥50% 5. Have recovered from the toxic effects of prior chemotherapies as per institutional guidelines 6. Are at least 2 weeks beyond any major tumor surgery and fully recovered from any post-surgical complications 7. Meet the following organ function criteria, as measured within 1 week prior to IMP dosing: a. BM function: i. Platelets ≥50 × 109/L ii. Absolute neutrophil count (ANC) ≥0.50 × 109/L b. Renal function: i. Age-adjusted serum creatinine ≤1.5 × ULN for age ii. eGFR at least 60 mL/min using the Schwartz formula c. Liver function: AST or ALT ≤3 × ULN and total bilirubin ≤1.5 × ULN. In case of liver metastases, AST or ALT ≤5 × ULN and total bilirubin ≤1.5 × ULN d. Cardiac function: i. Shortening fraction ≥27% or ejection fraction of ≥50% on echocardiogram ii. QTc on ECG using QTcF ≤ 450 msec e. Lung function: i. Pulse oximetry considered normal in room air, per Investigator judgment. No evidence of dyspnea at rest. f. CNS function: i. No clinical or radiological evidence of active CNS disease at the time of study enrollment ii. Participants with seizure disorders may be enrolled if seizures are well controlled on anti-seizure medications iii. No active CNS toxicity 8. Consent to pregnancy testing and use of an acceptable contraception method if applicable 9. If a fertile and sexually active male, agree to use condoms 10. Are willing and able to provide voluntary written informed assent 11. Parent or legal guardian is willing and able to provide and has provided voluntary written informed consent Sub Protocol A: a. Patients experiencing their first or second relapse having achieved disease stabilization or an initial response (SD, MR, PR or CR) to previous therapy b. If received prior anti-GD2 therapy, last dose administered at least 14 days previously and no ongoing toxicities c. If applicable, at least 6 weeks from AHCT following myeloablative therapy Sub Protocol B: a. HRNB participants who are first line refractory following a minimum of 4 cycles of induction chemotherapy with no history of PD, where refractory is defined as SD, MR or PR with at least one metastatic lesion remaining b. Identification of primary tumor documented c. Measurable disease by cross sectional imaging INRC, (Park, 2017).
Exclusion Criteria
- Any active uncontrolled infection at the time of enrollment. Any known history of infection with HIV, or active or chronic infection with HCV/HBV 2. Any contraindications to any of the study treatments. 3. Patients with >Grade 2 diarrhea. 4. Patients with disease of any major organ system. 5. Patients who have undergone a prior allogeneic stem cell transplant < 6 months ago or have undergone a solid organ transplant. 6. Patients who are on hemodialysis. 7. Patients who require or are likely to require pharmacologic doses of systemic corticosteroids. 8. Patients on any other immunosuppressive medications 9. Patients who have received enzyme-inducing anticonvulsants for at least 7 days prior to study enrollment. 10. Patients who have been diagnosed with any malignancy other than neuroblastoma. 11. Patients with symptoms of congestive heart failure. 12. Patients with a history of Grade 4 allergic reactions to anti-GD2 antibodies or reactions that required permanent discontinuation of the anti-GD2 therapy. 13. Patients involved in another blinded study or an IMP study within 14 days or 5 half-lives before Screening or during the study. 14. Females who are breastfeeding, pregnant or planning pregnancy. 15. Failure to meet the required washout periods before the first dose of hu14.18K322A 16. Ongoing need for any medication known or suspected to interfere with study treatment. 17. Any underlying condition that would jeopardise the safety of the participant Sub Protocol A: a. Patients with refractory only disease. b. Patients who progress during induction. c. Patients who failed to stabilize or respond to prior anti-GD2 mAb in combination with chemotherapy treatment. Sub Protocol B: a. Evidence of PD in the primary tumor, in metastatic soft tissue and skeletal site b. Initiation of consolidation or maintenance treatment. c. Prior anti-GD2 mAb therapy.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Denmark | Not Yet Recruiting | 01 Jul 2026 | 4 |
 France | Not Yet Recruiting | 01 Jul 2026 | 20 |
 Germany | Not Yet Recruiting | 01 Jul 2026 | 23 |
 Ireland | Not Yet Recruiting | 01 Jul 2026 | 9 |
 Spain | Not Yet Recruiting | 01 Jul 2026 | 55 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Temodal 5 mg hard capsules | Test | HARD CAPSULES | SOLUTION FOR INFUSION | 100 | 9 | PRD2864118 |
Daretabart | Test | SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | 60 | 9 | PRD13551251 |
IRINOTECAN | Test | — | SOLUTION FOR INFUSION | 50 | 9 | SUB08295MIG |