Active Ingredient: Naxitamab
Naxitamab is indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), for the treatment of pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy.
This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
For this indication, competent medicine agencies globally authorize below treatments:
For:
Intravenous, 3 milligrams naxitamab per kilogram of body weight, once every 2 days, 3 doses in total, over the duration of 4 weeks.
The recommended dosage of naxitamab is 3 mg/kg/day (up to 150 mg/day) on Days 1, 3, and 5 of each treatment cycle, administered as an intravenous infusion after dilution in combination with GM-CSF subcutaneously as shown in Table 1. Refer to the GM-CSF Prescribing Information for recommended dosing information.
Treatment cycles are repeated every 4 weeks until complete response or partial response, followed by 5 additional cycles every 4 weeks. Subsequent cycles may be repeated every 8 weeks. Discontinue naxitamab and GM-CSF for disease progression or unacceptable toxicity.
Administer pre-infusion medications and supportive treatment, as appropriate, during infusion.
The recommended dosage regimen for each treatment cycle is described below and in Table 1:
Table 1. Dose and Schedule of GM-CSF and Naxitamab Within One Treatment Cycle:
| Day | -4 | -3 | -2 | -1 | 0 | 1 | 2 | 3 | 4 | 5 |
|---|---|---|---|---|---|---|---|---|---|---|
| Subcutaneous GM-CSF | 250 µg/m²/day | 500 µg/m²/day | ||||||||
| Intravenous naxitamab | 3 mg/kg/day | 3 mg/kg/day | 3 mg/kg/day | |||||||
If a naxitamab dose is missed, administer the missed dose the following week by Day 10. Administer GM-CSF 500 µg /m²/day on the first day of the naxitamab infusion, and on the day before and on the day of the second and third infusion, respectively (i.e. a total of 5 days with 500 µg /m²/day).
Pain management prior to and during infusion:
Premedication: Reduce risk of infusion-related reactions and nausea/vomiting:
The recommended dosage modifications for naxitamab for adverse reactions are presented in Table 2.
Table 2. Recommended naxitamab dosage modifications for adverse reactions:
| Adverse Reaction | Severity* | Dosage Modifications |
|---|---|---|
| Infusion-related reactions | Grade 2 Defined as: Therapy or infusion interruption indicated but responds promptly to symptomatic treatment (e.g., antihistamines, NSAIDS, narcotics, IV fluids); prophylactic medications indicated for ≤24 hours | • Reduce naxitamab infusion rate to 50% of previous rate and monitor closely until recovery to Grade ≤ 1 • Increase infusion rate gradually to rate prior to the event as tolerated |
| Grade 3 Defined as: Prolonged (e.g., not rapidly responsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae | • Immediately interrupt naxitamab infusion and monitor closely until recovery to Grade ≤ 2 • Resume infusion at 50% of the rate prior to the event and increase infusion rate gradually to infusion rate prior to the event as tolerated. • Permanently discontinue naxitamab in patients not responding to medical intervention. | |
| Grade 4 infusion-related reactions Defined as: Life-threatening consequences: urgent intervention indicated or Grade 3 or 4 anaphylaxis | • Permanently discontinue naxitamab | |
| Pain | Grade 3 unresponsive to maximum supportive measures | • Permanently discontinue naxitamab |
| Reversible posterior leukoencephalopathy syndrome (RPLS) | All Grades | • Permanently discontinue naxitamab |
| Transverse myelitis | All Grades | • Permanently discontinue naxitamab |
| Peripheral neuropathy | Motor neuropathy: Grade 2 or greater or Sensory neuropathy: Grade 3 or 4 | • Permanently discontinue naxitamab |
| Neurological disorders of the eye | Grade 2 to 4 resulting in decreased visual acuity or limiting activities of daily living | • Withhold naxitamab until resolution • If resolved resume naxitamab at 50% of the prior dose; if tolerated without recurrence of symptoms, gradually increase naxitamab to dose prior to onset of symptoms • Permanently discontinue naxitamab if not resolved within 2 weeks or upon recurrence |
| Subtotal or total vision loss | • Permanently discontinue naxitamab | |
| Prolonged urinary retention | Persisting following discontinuation of opioids | • Permanently discontinue naxitamab |
| Hypertension | Grade 3 | • Withhold naxitamab or pause infusion until recovery to ≤ Grade 2 • Resume infusion at 50% of prior rate; if tolerated without recurrence of symptoms, gradually increase naxitamab to rate prior to onset of symptoms • Permanently discontinue naxitamab in patients not responding to medical intervention |
| Grade 4 | • Permanently discontinue naxitamab | |
| Other Adverse Reactions | Grade 3 | • Withhold naxitamab until recovery to Grade ≤ 2 • If resolved to Grade ≤ 2 resume naxitamab at same rate • Permanently discontinue naxitamab if not resolved to Grade ≤2 within 2 weeks |
| Grade 4 | • Permanently discontinue naxitamab |
* Based on Common Terminology Criteria for Adverse Events (CTCAE) v 5.0
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