Naxitamab plus stepped-up dosing of granulocyte–macrophage colony-stimulating factor for primary refractory high-risk neuroblastoma: results of a phase I/II trial

Background With high-risk neuroblastoma, post-induction metastases in bone marrow (BM)/bones confers a poor prognosis but can respond to anti-G D2 antibody, such as naxitamab. We report results of a phase I/II trial. Methods Cycles included GM-CSF and naxitamab infused (30-to-90 min) on days + 1, + 3, + 5. Naxitamab was dose-escalated in the trial’s phase I portion and administered at 9 mg/kg/cycle (i.e., ~ 270 mg/m 2 /cycle)—the recommended phase II dosage (RP2D)—in the phase II expansion. Cycles were monthly × 5 after a major response, i.e., complete (CR) or partial response. Results Among 32 subjects, CR was noted in 24 (75%), including 12 by international criteria and 12 based on MIBG-avid sites with negative PET scans. BM CR was achieved in 22/23 with BM metastases. Of 29 patients with abnormal 123 I-MIBG scans, major responses occurred in 14/20 with Curie scores (CS) 10–25 and in 7/9 with CS 1–9. Of 9 patients previously treated with other anti-G D2 antibodies, 5 became event-free survivors. Post-protocol, 18 patients received anti-neuroblastoma vaccine. Five-year progression-free/overall survival rates were 38%/64%. Baseline CS, prior 2nd-line therapy, and prior anti-G D2 antibody did not significantly impact survival. Conclusions Naxitamb + GM-CSF is an attractive option for primary refractory osteomedullary disease, including in patients with a high disease burden. Clinical trials registration Clinicaltrials.gov NCT01757626.