A phase II trial of naxitamab plus stepped-up dosing of GM-CSF for patients with high-risk neuroblastoma in first complete remission Journal Article
| Authors: | Kushner, B. H.; Modak, S.; Mauguen, A.; Basu, E. M.; Kramer, K.; Roberts, S. S.; Cheung, I. Y.; Cheung, N. K. V. |
| Article Title: | 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 mAb 3F8. In an international trial, naxitamab + GM-CSF was effective against chemoresistant high-risk neuroblastoma (HR-NB), leading to approval by the FDA. We now report results with patients in first 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 of patients with HR-NB in first 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 five cycles and comprised (i) subcutaneously administered priming doses of GM-CSF 250 μg/m2/day on days –4 to –0 (Wednesday–Sunday), followed by a step-up to 500 μg/m2/day on days +1 to +5 (Monday–Friday) and (ii) naxitamab infused intravenously (30–90”) on days +1, +3, and +5 (Monday–Wednesday–Friday, i.e., three doses/cycle). The dosage of naxitamab was 3 mg/kg/infusion (9 mg/kg/cycle, i.e., ∼270 mg/m2/cycle). The dosage of isotretinoin was 160 mg/m2/day started after cycle 2, ×14 days/course, and ×6 courses. Results: Fifty-nine patients with HR-NB (53 stage 4, 6 stage 3) were enrolled from February 2017 to July 2020. At 36 months, event-free/overall survival rates were 73%/93%, but 50 of 59 patients received after protocol treatment (vaccine and/or difluoromethylornithine). Six of 18 relapses were isolated in the central nervous system. Longer time from diagnosis to enrollment was a significantly adverse prognostic factor (P = 0.04). Twenty-one of 59 patients took no isotretinoin. Treatment was tolerable allowing outpatient administration. Conclusions: Naxitamab + GM-CSF is a good option to consolidate first CR of patients with HR-NB, including those who did not undergo autologous stem-cell transplantation. Efforts to prevent central nervous system relapse are warranted. ©2025 American Association for Cancer Research. |
| Keywords: | adolescent; adult; child; preschool child; child, preschool; genetics; clinical trial; mortality; antineoplastic agent; phase 2 clinical trial; antineoplastic combined chemotherapy protocols; granulocyte macrophage colony stimulating factor; pathology; monoclonal antibody; immunoglobulin g; infant; neuroblastoma; multicenter study; remission; remission induction; isotretinoin; drug therapy; 3f8 antibody; granulocyte-macrophage colony-stimulating factor; antibodies, monoclonal, murine-derived; antibodies, monoclonal, humanized; humans; human; male; female |
| Journal Title: | Clinical Cancer Research |
| Volume: | 31 |
| Issue: | 10 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2025-05-15 |
| Start Page: | 1877 |
| End Page: | 1884 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-24-3427 |
| PUBMED: | 40067131 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Brian H. Kushner -- Source: Scopus |
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