Naxitamab Added to Induction for Newly Diagnosed High-Risk Neuroblastoma

Summary

Objectives

This is a prospective, multicenter clinical trial in subjects with newly diagnosed
high-risk neuroblastoma to evaluate the efficacy and safety of administering naxitamab
with standard induction therapy.

All subjects will be followed for disease response, event free survival, overall survival
and toxicity. Extent of disease will be measured and assessed for changes throughout the
course of the study. All efficacy analyses will be performed on the evaluable population
which will consist of all enrolled subjects (subjects who initiate treatment with
naxitamab in combination with GM-CSF plus standard induction therapy) and who have
measurable disease at baseline.

The initial chemotherapy Induction regimen will utilize sequential administration of 5
cycles of multi-agent chemotherapy. Naxitamab will be added to all 5 Induction cycles.

Stem cell mobilization and collection will occur after the 2nd cycle of induction.

Surgical resection of the primary tumor will ideally occur after the 4th cycle of
Induction but may be delayed until after the 5th cycle of Induction if medically
necessary.

Disease status evaluations will occur at the following time points: (1) pre-treatment,
(2) post Cycle 2 Induction (3) Prior to surgical resection (if performed), (4) End of
Induction (which includes surgery and 5 cycles of chemotherapy), and (5) End of
Additional/Salvage Therapy as needed.

The current standard of care for high-risk neuroblastoma involves 5-7 cycles of induction
chemotherapy with surgical removal of the tumor after 4-5 cycles of chemotherapy,
followed by high-dose chemotherapy plus autologous stem cell transplant, then radiation
to the primary tumor bed, followed by anti-GD2 immunotherapy and cis retinoic acid. This
results in a less than 60% disease free survival for high-risk NB, a survival rate that
still greatly needs improvement. Two areas in which improvements can be made include: 1)
to improve response rate to induction chemotherapy and 2) to improve EFS by improving
maintenance therapy to prevent relapse.

We hypothesize that the addition of anti-GD2 therapy to induction chemotherapy will
result in improved end of induction responses and improved survival.