Naxitamab-gqgk, a recombinant humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against glycolipid disialoganglioside (GD2), is an antineoplastic agent.1
Naxitamab-gqgk is used, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), for the treatment of pediatric patients ≥1 year of age and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have experienced a partial response, a minor response, or stable disease with prior therapy.1 The accelerated approval of naxitamab-gqgk is based on overall response rate (ORR) and duration of response.1, 2 Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory studies.1 Naxitamab-gqgk has been designated an orphan drug by FDA for use in this condition.3
Efficacy of naxitamab-gqgk for relapsed or refractory high-risk neuroblastoma is based principally on the results of 2 open-label, single-arm trials (Study 201 and Study 12-230).1 Both trials evaluated the efficacy of naxitamab in combination with GM-CSF in a subpopulation of patients with refractory or relapsed high-risk neuroblastoma in the bone or bone marrow.1 The primary measure of efficacy was ORR based on the revised International Neuroblastoma Response Criteria as assessed by independent pathology and imaging review, along with confirmation in at least 1 subsequent assessment.1 Duration of response was additionally evaluated.1 All patients had received ≥1 prior systemic therapy to treat disease outside of the bone or bone marrow that resulted in a partial response, minor response, or stable disease; those with progressive disease were excluded.1 Naxitamab was administered at a dosage of 3 mg/kg by IV infusion on days 1, 3, and 5 of each cycle.1 Subcutaneous GM-CSF was administered at a dosage of 250 mcg/m2/day on days -4 to 0 and a dosage of 500 mcg/m2/day on days 1 to 5.1 Preplanned radiation was permitted in each study.1
In Study 201 (NCT03363373), 22 patients were included in the efficacy analysis.1 The median age of patients was 5 years (range: 3-10 years); 59% were male, 45% were white and 50% were Asian.1 At the time of diagnosis, 86% of patients had stage 4 disease according to the International Neuroblastoma Staging System (INSS); 64% had refractory disease and 36% had relapsed disease.1 The ORR, complete response rate, and partial response rates were 45, 36, and 9%, respectively, in patients receiving naxitamab with GM-CSF; the median duration of response was 6.2 months.1
In Study 12-230 (NCT01757626), 38 patients were included in the efficacy analysis.1 The median age of patients was 5 years (range: 2-23 years); 50% were male and 74% were White.1 At the time of diagnosis, 95% had stage 4 disease according to the INSS; 45% had refractory disease and 55% had relapsed disease.1 The ORR, complete response rate, and partial response rates were 34, 26, and 8%, respectively, in patients receiving naxitamab with GM-CSF; the proportion of responders with a duration of response ≥6 months was 23%.1
The prognosis for patients with recurrent high-risk neuroblastoma is generally poor even with intensive treatment.100 There is no standard treatment regimen; clinical trial participation and palliative care may be considered for these patients.100 Treatment options for recurrent or refractory high-risk neuroblastoma include chemotherapy combined with immunotherapy (e.g., temozolomide, irinotecan, and dinutuximab), iodine-131 meta-iodobenzylguanidine (alone, in combination with other treatments, or followed by stem cell transplant), anaplastic lymphoma kinase inhibitors (e.g., crizotinib), chemotherapy, and immunotherapy (e.g., naxitamab in combination with GM-CSF).100
Naxitamab-gqgk is administered by IV infusion after dilution.1 Do not administer by rapid IV injection, such as an IV push or bolus.1 Administer infusions on days 1, 3, and 5 of each treatment cycle; treatment cycles are repeated every 4 weeks until complete or partial response, followed by 5 additional cycles every 4 weeks.1 Subsequent cycles may be repeated every 8 weeks.1
Administer subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF) daily beginning 5 days prior to naxitamab infusion (day -4) through day 5. On days 1, 3, and 5, administer GM-CSF at least 1 hour prior to naxitamab infusion.
If a dose of naxitamab is missed, administer the dose the following week by day 10. Administer GM-CSF 500 mcg/m2/day on the first day of the naxitamab infusion and on the day before and the day of the second and third infusion in the treatment cycle (i.e., total of 5 days receiving 500 mcg/m2/day).
Store unopened vials of naxitamab-gqgk at 2-8°C in the original outer carton packaging to protect from light.
Each vial of naxitamab-gqgk solution for injection contains 40 mg/10 mL. Inspect each vial visually prior to use; discard if solution is discolored, cloudy, or contains particulates.
Add appropriate quantities of 5% albumin (human) and 0.9% sodium chloride injection based on the calculated naxitamab dosage (volume) to an empty, sterile IV bag as directed in the manufacturer's labeling.
Allow passive mixing for 5-10 minutes.1 Withdraw the required volume of naxitamab and add to infusion bag containing the 5% albumin/0.9% sodium chloride solution.1 Discard any partially used vials; each vial is intended for single use only.1
If immediate administration is not possible, may store the diluted solution at room temperature (15-25°C) for up to 8 hours or at 2-8°C for up to 24 hours.1 Once removed from refrigeration, start the infusion within 8 hours.1
IV infusions of naxitamab should be administered over 60 minutes for the first infusion (Cycle 1 Day 1) and over 30-60 minutes as tolerated for subsequent infusions.
The recommended dosage of naxitamab-gqgk in pediatric patients ≥1 year of age is 3 mg/kg/day (up to a maximum dose of 150 mg/day) by IV infusion on days 1, 3, and 5 of each treatment cycle.1
Naxitamab is given in combination with subcutaneous GM-CSF at a dosage of 250 mcg/m2/day on days -4 to 0 and a dosage of 500 mcg/m2/day on days 1 to 5.1 Refer to the GM-CSF prescribing information for additional dosing information.
Repeat treatment cycles every 4 weeks until a complete or partial response is achieved, followed by 5 additional 4-week cycles.1 Subsequent treatment cycles may be repeated every 8 weeks.1 Continue treatment until disease progression or unacceptable toxicity.1
The recommended dosage of naxitamab-gqgk is 3 mg/kg/day (up to a maximum dose of 150 mg/day) by IV infusion on days 1, 3, and 5 of each treatment cycle.1
Naxitamab is given in combination with subcutaneous GM-CSF at a dosage of 250 mcg/m2/day on days -4 to 0 and a dosage of 500 mcg/m2/day on days 1 to 5.1 Refer to the GM-CSF prescribing information for additional dosing information.
Treatment cycles are repeated every 4 weeks until a complete or partial response is achieved, followed by 5 additional 4-week cycles.1 Subsequent treatment cycles may be repeated every 8 weeks.1 Continue treatment until disease progression or unacceptable toxicity.1
Therapy Modification for Toxicity
If adverse effects occur, reduction in the infusion rate, temporary interruption of the infusion, or discontinuance of naxitamab may be necessary.1
If a grade 2 infusion-related reaction occurs (i.e., infusion interruption is indicated, but patient responds promptly to symptomatic treatment; prophylactic medications indicated for ≤24 hours), reduce naxitamab infusion rate by 50%.1 Monitor patient closely until recovery to grade ≤1; infusion rate may be gradually increased to the previous rate as tolerated.1
If a grade 3 infusion-related reaction occurs (i.e., prolonged reaction [not immediately responsive to symptomatic treatment and/or brief infusion interruption]; recurrence after initial improvement; or hospitalization indicated), immediately interrupt the infusion and monitor patient closely until recovery to grade ≤2.1 Subsequently, resume naxitamab infusion rate at 50% of the previous rate; infusion rate may be gradually increased to the previous rate as tolerated.1 In cases where the infusion-related reaction does not respond to medical intervention, permanently discontinue naxitamab.1
If a grade 4 infusion-related reaction occurs (i.e., urgent intervention indicated [potentially life-threatening]; or grade 3 or 4 anaphylaxis), permanently discontinue naxitamab.1
If grade 3 pain that is unresponsive to maximum supportive measures occurs, permanently discontinue naxitamab.1
If RPLS of any grade occurs, permanently discontinue naxitamab.1
If transverse myelitis of any grade occurs, permanently discontinue naxitamab.1
If grade 2 or higher peripheral motor neuropathy or grade 3 or 4 peripheral sensory neuropathy occurs, permanently discontinue naxitamab.1
If a grade 2 to 4 neurological disorder of the eye occurs (i.e., decreases visual acuity or limits activities of daily living), temporarily interrupt therapy until resolution.1 If resolved, naxitamab may be resumed at 50% of the previous dose; if tolerated without recurrence of symptoms, gradually increase back to dose administered prior to the onset of symptoms.1 Permanently discontinue naxitamab if symptoms do not resolve within 2 weeks or if the adverse reaction recurs.1
If subtotal or total vision loss occurs, permanently discontinue naxitamab.1
If prolonged urinary retention continues following discontinuation of opioid analgesics, permanently discontinue naxitamab.1
If grade 3 hypertension occurs, temporarily withhold, or interrupt the infusion and monitor patient closely until recovery to grade ≤2.1 Subsequently, resume naxitamab infusion rate at 50% of the previous rate; infusion rate may be gradually increased to the previous rate as tolerated.1 In cases where hypertension does not respond to medical intervention, permanently discontinue naxitamab.1
If grade 4 hypertension occurs, permanently discontinue naxitamab.1
If any other grade 3 adverse effects occur, temporarily withhold until recovery to grade ≤2.1 Subsequently, resume naxitamab infusion at the previous infusion rate.1 Permanently discontinue naxitamab if symptoms do not resolve to grade ≤2 within 2 weeks.1
If any other grade 4 adverse reaction occurs, permanently discontinue naxitamab.1
The manufacturer makes no specific dosage recommendations for patients with hepatic impairment.1
The manufacturer makes no specific dosage recommendations for patients with renal impairment.1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
Serious Infusion-related Reactions
A boxed warning about the risk of serious infusion-related reactions is included in the prescribing information for naxitamab-gqgk.1 Naxitamab can cause serious infusion reactions resulting in the need for urgent intervention such as fluid resuscitation, use of bronchodilators and corticosteroids, temporary interruption of the infusion or a reduction in the infusion rate, or admission to the intensive care unit.1 Symptoms observed in clinical trials included hypotension, bronchospasm, hypoxia, and stridor.1
During clinical trials, 4% of patients in Study 201 and 18% of patients in Study 12-230 experienced a serious infusion-related reaction with naxitamab-gqgk.1 Grade 3 or 4 infusion reactions occurred in 68 and 32% of patients in Studies 201 and 12-230, respectively.1 In Study 201, anaphylaxis was reported in 12% of patients, resulting in permanent discontinuation of naxitamab-gqgk in 2 patients (8%).1 In Study 12-230, 1 patient (1.4%) experienced a grade 4 cardiac arrest 1.5 hours after completion of naxitamab-gqgk infusion.1
Infusion-related reactions of any grade occurred in 100 and 94% of patients in Studies 201 and 12-230, respectively.1 Hypotension of any grade occurred in 100 and 89% of patients in Studies 201 and 12-230, respectively.1
Infusion reactions generally occur within 24 hours of the completion of naxitamab infusion; most occur within 30 minutes after the start of the infusion.1 Infusion reactions were more common during the first infusion of naxitamab within each treatment cycle.1 In Study 201, 80% of patients required a reduction in the infusion rate and 80% required temporary interruption of the infusion due to ≥1 infusion-related reaction.1
To mitigate the risks of infusion-related reactions, premedicate with an antihistamine, acetaminophen, an H2 antagonist, and corticosteroid.1 Monitor for infusion-related reactions during and for ≥2 hours after the completion of each naxitamab infusion; cardiopulmonary resuscitation medication and equipment should be available.1
If an infusion-related reaction occurs, institute appropriate medical management and reduce the infusion rate, interrupt the infusion, or permanently discontinue naxitamab based on the severity of the reaction.1
A boxed warning about the risk of neurotoxicity is included in the prescribing information for naxitamab.1 Naxitamab can cause severe neurotoxicity, including severe neuropathic pain, transverse myelitis, and reversible posterior leukoencephalopathy syndrome (RPLS).1
Pain with naxitamab-gqgk was reported in 100 and 94% of patients in Studies 201 and 12-230, respectively; types of pain included abdominal pain, bone pain, neck pain, and extremity pain.1 In Study 201, 72% of patients experienced grade 3 pain and one patient (4%) required temporary interruption of the infusion due to pain; pain most commonly occurred during the infusion and the median duration of pain was <1 day (range <1-62 days).1
To reduce pain associated with naxitamab, premedicate with a prophylactic medication for neuropathic pain (e.g., gabapentin) and oral opioids.1 Administer IV opioids as needed for breakthrough pain during the infusion.1 If grade 3 pain that is unresponsive to maximum supportive measures occurs, permanently discontinue naxitamab.1
Transverse myelitis has been reported with naxitamab-gqgk; permanently discontinue the drug if this occurs.1
Two patients (2.8%) experienced RPLS (also referred to as posterior reversible encephalopathy syndrome or PRES) during Study 12-230.1 The events occurred 2 and 7 days following completion of the first cycle of naxitamab.1 Monitor blood pressure and assess for neurologic symptoms during and following naxitamab infusion.1 If symptomatic RPLS occurs, permanently discontinue naxitamab.1
Peripheral neuropathy with naxitamab-gqgk was reported in 32 and 25% of patients in Studies 201 and 12-230, respectively; peripheral sensory neuropathy, peripheral motor neuropathy, paresthesia, and neuralgia were reported.1 Neuropathy most commonly began on the day of the infusion and lasted a median of 5.5 days (range 0-22 days) in Study 201 and 0 days (range 0-22 days) in Study 12-230.1 Permanent discontinuation of naxitamab may be warranted based on the type and severity of the neuropathy.1
Neurological disorders of the eye with naxitamab-gqgk were reported in 24 and 19% of patients in Studies 201 and 12-230, respectively; symptoms included unequal pupils, blurred vision, accommodation disorder, mydriasis, visual impairment, and photophobia.1 The median duration of neurological disorders of the eye was 17 days (range 0-84 days) and 1 day (range <1-21 days) in Studies 201 and 12-230, respectively.1 Two patients (8%) in Study 201 had not recovered from the adverse event at the time of data collection.1 Permanent discontinuation of naxitamab may be warranted based on the type and severity of the neurological disorders of the eye.1
Urinary retention with naxitamab-gqgk was reported in 4% of patients in both Study 201 and Study 12-230.1 All events occurred on the day of the infusion and lasted between 0-24 days.1 If prolonged urinary retention continues following discontinuation of opioid analgesics, permanently discontinue naxitamab.1
Other Warnings and Precautions
Hypertension with naxitamab-gqgk was reported in 44 and 28% of patients in Studies 201 and 12-230, respectively.1 Grade 3 or 4 hypertension occurred in 4 and 7% of patients in Studies 201 and 12-230, respectively.1 In Study 12-230, hypertension led to permanent discontinuation of naxitamab-gqgk in 4 patients (6%).1 Hypertension most commonly occurred on the day of the infusion, with events reported up to 9 days following the infusion.1
Do not administer naxitamab to patients with uncontrolled hypertension.1 Monitor blood pressure during each naxitamab infusion and at least daily on days 1 to 8 of each treatment cycle; monitor for complications of hypertension such as RPLS.1 Temporary interruption of the infusion, reduction in the infusion rate, or permanent discontinuation of naxitamab may be warranted based on the severity of the adverse effect.1
Fetal/Neonatal Morbidity and Mortality
Naxitamab may cause fetal harm when administered to pregnant females based on its mechanism of action.1 Advise females of reproductive potential to use effective contraceptive methods while receiving naxitamab and for 2 months after the last dose.1 Apprise patients of the potential hazard to the fetus if naxitamab is used during pregnancy.1
Naxitamab may cause fetal harm when administered to pregnant females based on its mechanism of action.1 There are no data available on outcomes if naxitamab is used during pregnancy.1 Apprise patients of the potential hazard to the fetus if naxitamab is used during pregnancy.1
The manufacturer states that pregnancy status should be verified prior to initiation of naxitamab therapy in females of reproductive potential and states that such females should be advised to use effective contraceptive methods while receiving naxitamab and for 2 months after the last dose.1
It is not known whether naxitamab is distributed into human milk.1 The effects of the drug on breast-fed infants or on the production of milk are also unknown.1 Because of the potential for adverse effects to naxitamab in breast-fed infants, advise women not to breast-feed while receiving the drug and for 2 months after the last dose.1
The safety and effectiveness of naxitamab-gqgk for its FDA-labeled neuroblastoma indication have been established in pediatric patients ≥1 year of age.1 The median age (range) of patients included in Studies 201 and 12-230 was 5 years (3-10 years) and 5 years (2-23 years), respectively.1
The safety and effectiveness of naxitamab-gqgk have not been established in pediatric patients <1 year of age.1
Patients ≥65 years of age were not included in clinical trials of naxitamab-gqgk as neuroblastoma primarily affects pediatric and young adult patients.1
The pharmacokinetics of naxitamab-gqgk have not been studied in patients with hepatic impairment; naxitamab is not expected to be metabolized by hepatic enzymes.2, 1
The pharmacokinetics of naxitamab-gqgk have not been studied in patients with renal impairment; naxitamab is not expected to be eliminated renally.1, 2
The most common adverse effects (≥25%) in patients receiving naxitamab-gqgk in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) are infusion-related reaction, 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.1
The most common grade 3 or 4 laboratory abnormalities (≥5%) in patients receiving naxitamab-gqgk in combination with GM-CSF are 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.1
Formal interaction studies have not been performed with naxitamab-gqgk.1, 2 Naxitamab is not known to be metabolized by the cytochrome P-450 (CYP) system or other drug-metabolizing enzymes.1, 2
Naxitamab is a humanized anti-glycolipid disialoganglioside (anti-GD2) monoclonal IgG1 antibody.1, 4 Naxitamab binds GD2, a glycolipid expressed on cells of neuroectodermal origin, including neuroblasts and CNS and peripheral nerves.1, 5 Following binding of naxitamab to GD2, cell lysis occurs through complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC).4, 5 Administration of subcutaneous granulocyte-macrophage colony-stimulating factor with naxitamab enhances granulocyte-mediated ADCC of neuroblastoma cells.6 As compared to dinutuximab, a chimeric human-murine anti-GD2 monoclonal antibody that is FDA-labeled for the treatment of pediatric patients with high-risk neuroblastoma, naxitamab has a 10-times higher affinity for GD2 in neuroblastoma xenograph models.6, 8
Exposure to naxitamab increases proportionally with increasing doses.6 Naxitamab is expected to be metabolized in the same way as endogenous IgG1, through degradation into small peptides via catabolic pathways.1 The mean terminal half-life of the drug is 8.2 days.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Naxitamab-gqgk is obtained through participating specialty distributors.7
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection concentrate, for IV infusion | 4 mg/mL | Danyelza® | Y-mAbs Therapeutics |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions July 24, 2023. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. Y-mAbs Therapeutics, Inc. DANYELZA® (naxitamab-gqgk) intravenous prescribing information. 2020 Nov.
2. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 761171Orig1s000: Multidisciplinary Review. [Web]
3. US Food and Drug Administration. Search orphan drug designations and approvals. [Web]
4. Markham A. Naxitamab: first approval. Drugs. 2021;81(2):291-296.
5. Furman WL. Monoclonal antibody therapies for high risk neuroblastoma. Biologics. 2021;15:205-219.
6. Kushner BH, Cheung IY, Modak S, et al. Humanized 3F8 anti-GD2 monoclonal antibody dosing with granulocyte-macrophage colony-stimulating factor in patients with resistant neuroblastoma: a phase 1 clinical trial. JAMA Oncol. 2018;4(12):1729-1735.
7. Y-mAbs Therapeutics, Inc. How to order DANYELZA. From Y-mAbs website. Accessed 2022 Jan 10. [Web]
8. United Therapeutics Corporation. UNITUXIN (dinutuximab) intravenous prescribing information. 2020 Sept. [Web]
100. National Cancer Institute. Neuroblastoma Treatment (PDQ®)-Health Professional Version. From NIH website. [Web]