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FDA Grants Accelerated Approval to Naxitamab for High-Risk Neuroblastoma in Bone or Bone Marrow


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On November 25, the U.S. Food and Drug Administration (FDA) granted accelerated approval to naxitamab (Danyelza) in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) for pediatric patients aged 1 year and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow demonstrating a partial response, minor response, or stable disease to prior therapy.

Naxitamab is a humanized anti-GD2 monoclonal antibody with high receptor affinity.

Study 201 and Study 12-230

Efficacy was evaluated in patients with relapsed or refractory neuroblastoma in the bone or bone marrow enrolled in two single-arm, open-label trials: Study 201 and Study 12-230. Patients with progressive disease following their most recent therapy were excluded. Patients received 3 mg/kg of naxitamab administered as an intravenous infusion on days 1, 3, and 5 of each 4-week cycle in combination with GM-CSF subcutaneously at 250 µg/m2/d on days −4 to 0 and at 500 µg/m2/d on days 1 to 5. At the investigator’s discretion, patients were permitted to receive preplanned radiation to the primary disease site in Study 201, and radiation therapy to nontarget bony lesions or soft-tissue disease in Study 12-230.

The main efficacy outcome measures were confirmed overall response rate per the revised International Neuroblastoma Response Criteria, as well as duration of response.

Among 22 patients treated in the multicenter Study 201, the overall response rate was 45% (95% confidence interval [CI] = 24%–68%), and 30% of responders had a duration of response of 6 months or longer. Among 38 patients treated in the single-center Study 12-230, the overall response rate was 34% (95% CI = 20%–51%), with 23% of patients having a duration of response of 6 months or longer. For both trials, responses were observed in either the bone, bone marrow, or both.

The prescribing information contains a Boxed Warning stating that naxitamab can cause serious infusion-related reactions and neurotoxicity, including severe neuropathic pain, transverse myelitis, and reversible posterior leukoencephalopathy syndrome. To mitigate these risks, patients should receive premedication prior to each naxitamab infusion and be closely monitored during and for at least 2 hours following completion of each infusion.

The most common adverse reactions (incidence ≥ 25% in either trial) in patients receiving naxitamab were infusion-related reactions, pain, tachycardia, vomiting, cough, nausea, diarrhea, decreased appetite, hypertension, fatigue, erythema multiforme, peripheral neuropathy, urticaria, pyrexia, headache, injection site reaction, edema, anxiety, localized edema, and irritability. The most common grade 3 or 4 laboratory abnormalities (≥ 5% in either trial) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased platelet count, decreased potassium, increased alanine aminotransferase, decreased glucose, decreased calcium, decreased albumin, decreased sodium, and decreased phosphate.

The recommended naxitamab dose is 3 mg/kg/d (up to 150 mg/d) on days 1, 3, and 5 of each treatment cycle, administered after dilution as an intravenous infusion in combination with GM-CSF, subcutaneously at 250 µg/m2/d on days −4 to 0 and at 500 µg/m2/d on days 1 to 5. Treatment cycles are repeated every 4 to 8 weeks.


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