A phase II trial of Naxitamab plus stepped-up dosing of GM-CSF for patients with high-risk neuroblastoma in first complete remission

Abstract Purpose: Naxitamab is a humanized form of the murine anti-GD2 monoclonal antibody (mAb) 3F8. In an international trial, naxitamab+GM-CSF was effective against chemo-resistant high-risk neuroblastoma (HR-NB), leading to approval by the Food and Drug Administration. We now report results with patients in 1st complete remission (CR). Patients and Methods: The primary objective of this phase II protocol 16-1643 (Clinicaltrials.gov NCT03033303) was to assess event-free survival (EFS) of HR-NB patients in 1st CR treated with naxitamab+GM-CSF plus isotretinoin. HR-NB was defined as MYCN-amplified disease (any age) or metastatic disease at age >18 months. Cycles of immunotherapy were administered monthly up to 5 cycles and comprised: 1) subcutaneously-administered priming doses of GM-CSF 250µg/m2/day on days -4-to-0 (Wednesday-Sunday), followed by a step-up to 500µg/m2/day on days +1-to-+5 (Monday-Friday), and 2) naxitamab infused intravenously (30-90”) on days +1, +3, and +5 (Monday-Wednesday-Friday, i.e., 3 doses/cycle). Naxitamab was 3mg/kg/infusion (9mg/kg/cycle, i.e., ~270mg/m2/cycle). Isotretinoin 160mg/m2/day started post-cycle 2, x14 days/course, x6 courses. Results: Fifty-nine HR-NB patients (53 stage 4, 6 stage 3) were enrolled 2/2017-7/2020. At 36 months, EFS/OS were 73%/93%, but 50/59 patients received post-protocol treatment (vaccine and/or DFMO). 6/18 relapses were isolated in the central nervous system (CNS). Longer time from diagnosis to enrollment was a significantly adverse prognostic factor (p=0.04). 21/59 patients took no isotretinoin. Treatment was tolerable allowing outpatient administration. Conclusions: Naxitamab+GM-CSF is a good option to consolidate 1st CR of HR-NB patients, including those who did not undergo ASCT. Efforts to prevent CNS relapse are warranted.