Clinical Analysis of Naxitamab (hu3F8) in the Treatment of Pediatric High Risk or Refractory/ Relapsed Neuroblastoma

Study Overview
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Brief Summary
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This is an prospective study to evaluate the safety and efficacy of naxitamab monotherapy or combined with chemotherapy or combined with chemotherapy and checkpoint inhibitor in the treatment of pediatric high-risk and refractory/relapsed neuroblastoma in Sun Yat-sen University Cancer Center.

Detailed Description
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Patients with high risk neuroblastoma who obtain CR after chemotherapy combined with surgery, radiotherapy and/or hematopoietic stem cell transplantation received axitamab and GM-CSF. Patients with high-risk neuroblastoma treated by chemotherapy combined with surgery, radiotherapy and or hematopoietic stem cell transplantation patients with tumor residual or progression during treatment (refractory) received naxitamab and GM-CSF in combination with irinotecan and temozolomide or naxitamab and GM-CSF in combination with irinotecan and temozolomide and PD-1 antibody.

Official Title
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Clinical Analysis of Naxitamab (hu3F8) in the Treatment of Pediatric High Risk or Refractory/ Relapsed Neuroblastoma

Conditions
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Neuroblastoma

Intervention / Treatment
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* Drug: Naxitamab monotherapy
* Drug: GM-CSF
* Drug: Irinotecan
* Drug: Temozolomide
* Drug: Naxitamab in combination therapy
* Drug: GM-CSF with combination regimen
* Drug: Sintilimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1)Confirmed diagnosis of high-risk NB 2)1 year of age or above 3)Patient or parent/guardian must provide written informed consent to participate 4)If patient is sexually active, the patient agrees to use effective contraception 5)Confirmed negative urine pregnancy test for sexually active female of child-bearing potential (post-menarche) Exclusion Criteria: Significant organ toxicity Known or suspected allergy or hypersensitivity to anti-GD2 antibodies or to GM-CSF or its s components. Patient is pregnant, planning to become pregnant (while being treated with naxitamab) or is currently breastfeeding Patient will undergo treatment with another investigational drug, whilst being treated with naxitamab or has received another investigational drug within the 4 weeks prior to commencing treatment with naxitamab Patient is either eligible and able to participate in or is currently participating in an active interventional Y-mAbs sponsored clinical trial with naxitamab within the indication applied for Patient is unable to comply with the naxitamab treatment or has a medical condition that would potentially increase the severity of the toxicities experienced from naxitamab treatment at the discretion of the treating physician Left ventricular ejection fraction of <50% by echocardiography OR other clinically relevant cardiac disorders at the discretion of the investigator 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 Applicable for treatment with naxitamab in combination with GM-CSF only: Patient has active progression of the NB disease Patient has active NB disease at primary site or soft-tissue metastasis Patient has known CNS metastases when initiating naxitamab treatment

Ages Eligible for Study
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Minimum Age: 12 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: naxitamab and GM-CSF only<br>Suitable for patients with high risk neuroblastoma who obtain CR after chemotherapy combined with surgery, radiotherapy and/or hematopoietic stem cell transplantation. The treatment cycle is repeated every 4 weeks for a total of 5 courses, and discontinuation of nasetuzumab and GM-CSF should be considered if disease progression or unacceptable toxicity occurs. | Drug: Naxitamab monotherapy<br>* Naxitamab is administered on days 1, 3, and 5<br>* Other names: hu3F8;Drug: GM-CSF<br>* Each treatment cycle is 28 days and is started with five days (days -4 to 0) of GM-CSF administered at 250 mcg/m2/day in advance of the start of naxitamab infusion. GM-CSF is thereafter administered at 500 mcg/m2/day on days 1 to 5.<br>* Other names: Recombinant Human Granulocyte/Macrophage Colony-stimulating Factor;|
| Other: naxitamab and GM-CSF in combination with irinotecan and temozolomide<br>Suitable for high-risk group neuroblastoma treated by chemotherapy combined with surgery, radiotherapy and or hematopoietic stem cell transplantation patients with tumor residual or progression during treatment (refractory); Patients who relapse after initial treatment. Repeat every 3 weeks until tumor progression, patient withdrawal, or toxicity becomes intolerable, up to 8 procedures. | Drug: Irinotecan<br>* Each HITS treatment cycle is 21 days. Irinotecan intravenously (IV) at 50 mg/m2/day will be administered from Day 1-5 concurrently with temozolomide orally at 150 mg/m2/day or 100 mg/m2/day.<br>* Other names: DNA topoisomerase I inhibitor;Drug: Temozolomide<br>* Each HITS treatment cycle is 21 days. Irinotecan intravenously (IV) at 50 mg/m2/day will be administered from Day 1-5 concurrently with temozolomide orally at 150 mg/m2/day or 100 mg/m2/day.<br>* Other names: Temozolomide for Injection;Drug: Naxitamab in combination therapy<br>* Naxitamab 2.25mg/kg IV will be administered on Days 2, 4, 8 and 10.<br>* Other names: hu3F8;Drug: GM-CSF with combination regimen<br>* GM-CSF 250 mcg/m2/day will be administered subcutaneously on Days 6-10.<br>* Other names: Recombinant Human Granulocyte/Macrophage Colony-stimulating Factor;|
| Other: naxitamab and GM-CSF in combination with irinotecan and temozolomide and PD-1 antibody<br>Suitable for high-risk group neuroblastoma treated by chemotherapy combined with surgery, radiotherapy and or hematopoietic stem cell transplantation patients with tumor residual or progression during treatment (refractory); Patients who relapse after initial treatment. Repeat every 3 weeks until tumor progression, patient withdrawal, or toxicity becomes intolerable, up to 8 procedures. | Drug: Irinotecan<br>* Each HITS treatment cycle is 21 days. Irinotecan intravenously (IV) at 50 mg/m2/day will be administered from Day 1-5 concurrently with temozolomide orally at 150 mg/m2/day or 100 mg/m2/day.<br>* Other names: DNA topoisomerase I inhibitor;Drug: Temozolomide<br>* Each HITS treatment cycle is 21 days. Irinotecan intravenously (IV) at 50 mg/m2/day will be administered from Day 1-5 concurrently with temozolomide orally at 150 mg/m2/day or 100 mg/m2/day.<br>* Other names: Temozolomide for Injection;Drug: Naxitamab in combination therapy<br>* Naxitamab 2.25mg/kg IV will be administered on Days 2, 4, 8 and 10.<br>* Other names: hu3F8;Drug: GM-CSF with combination regimen<br>* GM-CSF 250 mcg/m2/day will be administered subcutaneously on Days 6-10.<br>* Other names: Recombinant Human Granulocyte/Macrophage Colony-stimulating Factor;Drug: Sintilimab<br>* Sintilimab was administerd with 3mg/kg (max 200mg) on day 11 every 3 weeks.<br>* Other names: PD-1 antibody;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | The proportion of patients who achieved CR or PR | from start of naxitamab treatment to 1.5 years after EOT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DCR | The proportion of patients who achieved CR or PR or SD | from start of naxitamab treatment to 1.5 years after EOT | 
| EFS | The time from from start of naxitamab treatment to disease progression, recurrence | from start of naxitamab treatment to 1.5 years after EOT | 
| OS | The time from from start of naxitamab treatment to death or loss of follow-up | from start of naxitamab treatment to 1.5 years after EOT |