Naxitamab for High-Risk Neuroblastoma Patients With Primary Refractory Disease or Incomplete Response to Salvage Treatment in Bone and/or Bone Marrow

A Pivotal Phase 2 Trial of Antibody Naxitamab (hu3F8) and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in High-Risk Neuroblastoma Patients With Primary Refractory Disease or Incomplete Response to Salvage Treatment in Bone and/or Bone Marrow

Children and adults diagnosed with high-risk neuroblastoma patients with primary refractory disease or incomplete response to salvage treatment in bone and/or bone marrow will be treated for up to 101 weeks with naxitamab and granulocyte-macrophage colony stimulating factor (GM-CSF). Patients will be followed for up to five years after first dose.

Naxitamab, also known as hu3F8 is a humanised monoclonal antibody targeting GD2

Study Overview

• Status: Recruiting
• Conditions: Neuroblastoma
• Intervention / Treatment: Biological: GM-CSF + Naxitamab

Detailed Description

Each patient will receive treatment for up to 101 weeks following the first Naxitamab administration. After the end of trial visit, each patient will enter a long-term follow-up where they will be monitored for up to 5 years after first treatment cycle.

Each investigational cycle is started with 5 days, days -4 to 0, of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) administered at 250 µg/m2/day in advance of the start of Naxitamab administration. GM-CSF is thereafter administered at 500 µg/m2/day on days 1 to 5. As standard treatment, Naxitamab is administered at 3 mg/kg/day on days 1, 3, and 5, totalling 9 mg/kg per cycle.

Treatment cycles are repeated every 4 weeks (±1 week) until complete response or partial response followed by 5 additional cycles every 4 weeks (±1 week). Subsequent cycles are repeated every 8 weeks (±2 weeks) through 101 weeks from first infusion at the discretion of the investigator. End of treatment will take place around 8 weeks after the last cycle and thereafter long-term follow-up will continue.

• Study Type: Interventional
• Enrollment (Estimated): 122
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rhiannon Wright; Phone Number: +447969051167; Email: clinicaltrials@ymabs.com

Study Locations

• Canada
  • Toronto, Canada, M5G 1X8
    • Recruiting
    • The Hospital for Sick Children
• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Rigshospitalet
• France
  • Marseille
    • Marseille, Marseille, France, 13005
      • Withdrawn
      • Hopital pour enfants de la Timone
• Germany
  • Hamburg, Germany
    • Recruiting
    • University Medical Center Hamburg-Eppendorf
  • Mainz, Germany
    • Recruiting
    • Johannes Gutenberg-Universität
  • Regensburg, Germany
    • Recruiting
    • University Hospital Regensburg
• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Hong Kong Children's Hospital
  • Hong Kong, Hong Kong
    • Active, not recruiting
    • Queen Mary Hospital
• India
  • Mumbai, India, 400012
    • Recruiting
    • Tata Memorial Centre
• Italy
  • Rome, Italy
    • Recruiting
    • Ospedale Pediatrico Bambino Gesu
  • Genoa
    • Genoa, Genoa, Italy, 16147
      • Recruiting
      • Giannina Gaslini Hospital
  • Milan
    • Milan, Milan, Italy, 20133
      • Recruiting
      • Fondazione IRCCS Istituto Nazionale dei Tumori
• Spain
  • Barcelona, Spain, 08950
    • Recruiting
    • Hospital Sant Joan de Déu
  • Madrid, Spain, 28009
    • Recruiting
    • Hospital Infantil Universitario Nino Jesus
  • Seville, Spain
    • Recruiting
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46026
    • Recruiting
    • Hospital Universitario y Politécnico La Fe
• United Kingdom
  • Glasgow, United Kingdom, G51 4TF
    • Recruiting
    • The Royal Glasgow Children's Hospital
  • Leeds, United Kingdom, LS1 3EX
    • Recruiting
    • Leeds General Infirmary
  • London, United Kingdom, SW3 6JJ
    • Withdrawn
    • The Royal Marsden
  • Southampton, United Kingdom, so16 6yd
    • Recruiting
    • University Hospital Southampton
• United States
  • Florida
    • Gainesville, Florida, United States, 32611
      • Withdrawn
      • University of Florida
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Withdrawn
      • University of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Active, not recruiting
      • Riley Hospital for Children
  • New York
    • New York, New York, United States, 10065
      • Active, not recruiting
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Withdrawn
      • Nationwide Children's Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Withdrawn
      • M.D. Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of neuroblastoma as defined per International Neuroblastoma Response Criteria
• High-risk neuroblastoma patients with either primary refractory disease or incomplete response to salvage treatment (in both cases including stable disease, minor response and partial response) evaluable in bone and/or bone marrow.
• Life expectancy ≥ 6 months

Exclusion Criteria:

• Any systemic anti-cancer therapy, including chemotherapy or immunotherapy, within 3 weeks before 1st dose of GM-CSF
• Evaluable neuroblastoma outside bone and bone marrow
• Existing major organ dysfunction > Grade 2, with the exception of hearing loss, hematological status, kidney and liver function
• Active life-threatening infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: GM-CSF + Naxitamab; Each investigational cycle is started with 5 days of GM-CSF administered at 250 µg/m2/day in advance of the start of Naxitamab administration. GM-CSF is thereafter administered at 500 µg/m2/day on days 1 to 5. As standard treatment, Naxitamab is administered at 3 mg/kg/day on days 1, 3, and 5 totalling 9 mg/kg per cycle. Treatment cycles are repeated every 4 weeks until CR or PR followed by 5 additional cycles every 4 weeks (±1 week). Subsequent cycles are repeated every 8 weeks (±2 weeks) through 101 weeks from first infusion at the discretion of the investigator. After end of treatment patients will enter a long-term follow up for up to 3 years after end of treatment visit.

Biological: GM-CSF + Naxitamab; Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Humanized IgG1 monoclonal GD2 antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate during Naxitamab treatment	Overall objective response rate (ORR) during the Naxitamab treatment period that will be centrally assessed according to the International Neuroblastoma Response Criteria (INRC) modified with 123I-MIBG criteria and following the use of 18F FDG-PET for MIBG non-avid lesions.	101 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events and serious adverse events	Safety will be evaluated by the incidence of adverse events (AE) and serious adverse events (SAEs) graded according to CTCAE, version 4.0.	101 weeks
Duration of Response (DoR)	Length of time from patient response to disease progression.	101 weeks
Complete Response Rate	The complete response (CR) rate is defined as the fraction of patients experiencing a CR according to International Neuroblastoma Response Criteria (INRC) criteria during the treatment period.	101 weeks
Assessment of the maximum serum concentration (cmax) of naxitamab	Calculation of maximum serum concentration of naxitamab will be calculated and summarized with descriptive statistics.	Pre-naxitamab dose - 552 hours
Assessment of the minimum serum concentration (cmin) of naxitamab	Calculation of minimum serum concentration of naxitamab will be calculated and summarized with descriptive statistics.	Pre-naxitamab dose - 552 hours
Assessment of the clearance of naxitamab	Calculation of clearance of naxitamab will be calculated and summarized with descriptive statistics.	Pre-naxitamab dose - 552 hours
Assessment of the volume of distribution of naxitamab	Calculation of the volume of distribution of naxitamab will be calculated and summarized with descriptive statistics.	Pre-naxitamab dose - 552 hours
Assessment of the Area under the Curve (AUC) of naxitamab	Calculation of the AUC of naxitamab will be calculated and summarized with descriptive statistics.	Pre-naxitamab dose - 552 hours
Assessment of the terminal half-life (t½) of naxitamab	Calculation of the t½ of naxitamab will be calculated and summarized with descriptive statistics.	Pre-naxitamab dose - 552 hours
Assessment of anti-drug antibody (ADA) formation	ADA formation will be investigated following a multi-tiered approach: A screening confirmation-titration analysis plus a ligand binding assay to examine a potential neutralizing effect of anti-naxitamab antibodies.	Pre-naxitamab dose - 552 hours
Intravenous (IV) opioid use (cycle 1)	IV opioid use during cycle 1 defined as total dosage of IV morphine (or equivalent opioid) administered 2 hours before infusion until 4 hours after end of infusion of naxitamab	6 hours
Intravenous (IV) opioid use (all cycles)	IV opioid use for each cycle during the trial defined as total dosage of IV morphine (or equivalent opioid) administered 2 hours before infusion until 4 hours after end of infusion of naxitamab	101 weeks
Hospitalization days (cycle 1)	Number of hospitalization days related to naxitamab during cycle 1, defined as number of overnight stays. Hospitalizations required solely for protocol-specified assessments (e.g., PK sampling) or non-medical circumstances are excluded	4 weeks
Safety of patients with positive human anti-drug antibody (ADA)	In patients with positive ADA at trial inclusion, safety will be evaluated by the incidence of AEs and SAEs graded according to CTCAE, version 4.0	101 weeks
Number of infusions done in an outpatient setting	Number of infusions done in an outpatient setting	101 weeks
Percentage of infusions done in an outpatient setting	Percentage of infusions done in an outpatient setting	101 weeks
Incidence of adverse events and serious adverse events in ADA positive patients	Safety will be evaluated by the incidence of adverse events (AE) and serious adverse events (SAEs) graded according to CTCAE, version 4.0 in ADA positive patients.	101 weeks
Progression Free Survival (PFS)	PFS, defined as the time from the first 1st infusion of naxitamab until progressive disease or death, whichever comes first	5 years
Overall Survival	The interval from the date of first dose of Naxitamab until the date of death due to any cause.	5 years
Happiness and activity levels	Happiness and activity levels will be measured over time and assessed by caretaker	39 days

Collaborators and Investigators

• Sponsor: Y-mAbs Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2018
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: November 6, 2017
• First Submitted That Met QC Criteria: December 5, 2017
• First Posted (Actual): December 6, 2017

Study Record Updates

• Last Update Posted (Actual): February 19, 2026
• Last Update Submitted That Met QC Criteria: February 17, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Antibody, Neuroblastoma, Pediatric, Adult
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neuroblastoma; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Carbohydrates; Intercellular Signaling Peptides and Proteins; Glycoproteins; Glycoconjugates; Colony-Stimulating Factors; Hematopoietic Cell Growth Factors; Cytokines; Granulocyte-Macrophage Colony-Stimulating Factor; naxitamab
• Other Study ID Numbers: 201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No