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The Food and Drug Administration has granted accelerated approval for naxitamab (Danyelza) to treat certain patients with neuroblastoma, based on response rates in two small trials.
Naxitamab is a humanized monoclonal antibody that targets GD2, a disialoganglioside highly expressed on neuroblastomas.
The FDA approved naxitamab for use in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) in adults and children aged 1 year and older who have relapsed or refractory, high-risk neuroblastoma in the bone or bone marrow that demonstrated a partial response, minor response, or stable disease to prior therapy.
Naxitamab was originally developed at Memorial Sloan Kettering Cancer Center in New York, and licensed exclusively to Y-mAbs Therapeutics. As a result of the licensing arrangement, MSKCC has institutional financial interests in the product, the company noted.
Study results
The accelerated approval of naxitamab was based on the overall response rate (ORR) and duration of response in two single-arm, open-label trials: Study 201 (NCT03363373) in 22 patients and Study 12-230 (NCT01757626) in 38 patients.
In both studies, patients received naxitamab at 3 mg/kg administered as an intravenous infusion on days 1, 3, and 5 of each 4-week cycle in combination with GM-CSF subcutaneously at 250 mcg/m2/day on days -4 to 0 and at 500 mcg/m2/day on days 1-5.
Some patients also received radiotherapy. At the investigator’s discretion, patients were permitted to receive preplanned radiation to the primary disease site in Study 201 and radiation to nontarget bony lesions or soft tissue disease in Study 12-230.
The ORR was 45% in Study 201 and 34% in Study 12-230. Responses were observed in the bone and/or bone marrow, the FDA noted.
Less than a third of patients had a duration of response that lasted 6 months or more – 30% of responders in Study 201 and 23% of responders in Study 12-230.
The FDA noted that continued approval of naxitamab may be contingent upon verification and description of clinical benefit in confirmatory trials.
The agency also noted that naxitamab was granted priority review, breakthrough therapy, and orphan drug designation. In addition, a priority review voucher was issued for the rare pediatric disease product application.
Boxed warning and adverse events
Naxitamab has a boxed warning about serious infusion-related reactions and neurotoxicity.
The product information notes that, in clinical studies, naxitamab has been shown to cause serious infusion reactions, including anaphylaxis, cardiac arrest, bronchospasm, stridor, and hypotension. Infusion reactions generally occurred within 24 hours of completing an infusion, most often within 30 minutes of initiation. Infusion reactions were most frequent during the first infusion in each cycle.
To mitigate these risks, Y-mAbs Therapeutics recommends premedication with an antihistamine, acetaminophen, an H2 antagonist, and corticosteroid, as well as close monitoring of patients during and for at least 2 hours after each infusion in a setting where cardiopulmonary resuscitation medication and equipment are available.
Based on its mechanism of action, naxitamab can cause severe pain, according to Y-mAbs Therapeutics. The company recommends premedication with gabapentin and, for example, oral oxycodone, and recommends treating break-through pain with intravenous hydromorphone or an equivalent intervention.
In addition, naxitamab may cause severe hypertension. The onset of hypertension may be delayed, so blood pressure should be monitored both during and after infusion.
The product insert also notes that one case of transverse myelitis (grade 3) and two cases of posterior reversible encephalopathy syndrome have been reported.
The most common adverse reactions (incidence ≥ 25% in either trial) 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.
A version of this article appeared on Medscape.com.
The Food and Drug Administration has granted accelerated approval for naxitamab (Danyelza) to treat certain patients with neuroblastoma, based on response rates in two small trials.
Naxitamab is a humanized monoclonal antibody that targets GD2, a disialoganglioside highly expressed on neuroblastomas.
The FDA approved naxitamab for use in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) in adults and children aged 1 year and older who have relapsed or refractory, high-risk neuroblastoma in the bone or bone marrow that demonstrated a partial response, minor response, or stable disease to prior therapy.
Naxitamab was originally developed at Memorial Sloan Kettering Cancer Center in New York, and licensed exclusively to Y-mAbs Therapeutics. As a result of the licensing arrangement, MSKCC has institutional financial interests in the product, the company noted.
Study results
The accelerated approval of naxitamab was based on the overall response rate (ORR) and duration of response in two single-arm, open-label trials: Study 201 (NCT03363373) in 22 patients and Study 12-230 (NCT01757626) in 38 patients.
In both studies, patients received naxitamab at 3 mg/kg administered as an intravenous infusion on days 1, 3, and 5 of each 4-week cycle in combination with GM-CSF subcutaneously at 250 mcg/m2/day on days -4 to 0 and at 500 mcg/m2/day on days 1-5.
Some patients also received radiotherapy. At the investigator’s discretion, patients were permitted to receive preplanned radiation to the primary disease site in Study 201 and radiation to nontarget bony lesions or soft tissue disease in Study 12-230.
The ORR was 45% in Study 201 and 34% in Study 12-230. Responses were observed in the bone and/or bone marrow, the FDA noted.
Less than a third of patients had a duration of response that lasted 6 months or more – 30% of responders in Study 201 and 23% of responders in Study 12-230.
The FDA noted that continued approval of naxitamab may be contingent upon verification and description of clinical benefit in confirmatory trials.
The agency also noted that naxitamab was granted priority review, breakthrough therapy, and orphan drug designation. In addition, a priority review voucher was issued for the rare pediatric disease product application.
Boxed warning and adverse events
Naxitamab has a boxed warning about serious infusion-related reactions and neurotoxicity.
The product information notes that, in clinical studies, naxitamab has been shown to cause serious infusion reactions, including anaphylaxis, cardiac arrest, bronchospasm, stridor, and hypotension. Infusion reactions generally occurred within 24 hours of completing an infusion, most often within 30 minutes of initiation. Infusion reactions were most frequent during the first infusion in each cycle.
To mitigate these risks, Y-mAbs Therapeutics recommends premedication with an antihistamine, acetaminophen, an H2 antagonist, and corticosteroid, as well as close monitoring of patients during and for at least 2 hours after each infusion in a setting where cardiopulmonary resuscitation medication and equipment are available.
Based on its mechanism of action, naxitamab can cause severe pain, according to Y-mAbs Therapeutics. The company recommends premedication with gabapentin and, for example, oral oxycodone, and recommends treating break-through pain with intravenous hydromorphone or an equivalent intervention.
In addition, naxitamab may cause severe hypertension. The onset of hypertension may be delayed, so blood pressure should be monitored both during and after infusion.
The product insert also notes that one case of transverse myelitis (grade 3) and two cases of posterior reversible encephalopathy syndrome have been reported.
The most common adverse reactions (incidence ≥ 25% in either trial) 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.
A version of this article appeared on Medscape.com.
The Food and Drug Administration has granted accelerated approval for naxitamab (Danyelza) to treat certain patients with neuroblastoma, based on response rates in two small trials.
Naxitamab is a humanized monoclonal antibody that targets GD2, a disialoganglioside highly expressed on neuroblastomas.
The FDA approved naxitamab for use in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) in adults and children aged 1 year and older who have relapsed or refractory, high-risk neuroblastoma in the bone or bone marrow that demonstrated a partial response, minor response, or stable disease to prior therapy.
Naxitamab was originally developed at Memorial Sloan Kettering Cancer Center in New York, and licensed exclusively to Y-mAbs Therapeutics. As a result of the licensing arrangement, MSKCC has institutional financial interests in the product, the company noted.
Study results
The accelerated approval of naxitamab was based on the overall response rate (ORR) and duration of response in two single-arm, open-label trials: Study 201 (NCT03363373) in 22 patients and Study 12-230 (NCT01757626) in 38 patients.
In both studies, patients received naxitamab at 3 mg/kg administered as an intravenous infusion on days 1, 3, and 5 of each 4-week cycle in combination with GM-CSF subcutaneously at 250 mcg/m2/day on days -4 to 0 and at 500 mcg/m2/day on days 1-5.
Some patients also received radiotherapy. At the investigator’s discretion, patients were permitted to receive preplanned radiation to the primary disease site in Study 201 and radiation to nontarget bony lesions or soft tissue disease in Study 12-230.
The ORR was 45% in Study 201 and 34% in Study 12-230. Responses were observed in the bone and/or bone marrow, the FDA noted.
Less than a third of patients had a duration of response that lasted 6 months or more – 30% of responders in Study 201 and 23% of responders in Study 12-230.
The FDA noted that continued approval of naxitamab may be contingent upon verification and description of clinical benefit in confirmatory trials.
The agency also noted that naxitamab was granted priority review, breakthrough therapy, and orphan drug designation. In addition, a priority review voucher was issued for the rare pediatric disease product application.
Boxed warning and adverse events
Naxitamab has a boxed warning about serious infusion-related reactions and neurotoxicity.
The product information notes that, in clinical studies, naxitamab has been shown to cause serious infusion reactions, including anaphylaxis, cardiac arrest, bronchospasm, stridor, and hypotension. Infusion reactions generally occurred within 24 hours of completing an infusion, most often within 30 minutes of initiation. Infusion reactions were most frequent during the first infusion in each cycle.
To mitigate these risks, Y-mAbs Therapeutics recommends premedication with an antihistamine, acetaminophen, an H2 antagonist, and corticosteroid, as well as close monitoring of patients during and for at least 2 hours after each infusion in a setting where cardiopulmonary resuscitation medication and equipment are available.
Based on its mechanism of action, naxitamab can cause severe pain, according to Y-mAbs Therapeutics. The company recommends premedication with gabapentin and, for example, oral oxycodone, and recommends treating break-through pain with intravenous hydromorphone or an equivalent intervention.
In addition, naxitamab may cause severe hypertension. The onset of hypertension may be delayed, so blood pressure should be monitored both during and after infusion.
The product insert also notes that one case of transverse myelitis (grade 3) and two cases of posterior reversible encephalopathy syndrome have been reported.
The most common adverse reactions (incidence ≥ 25% in either trial) 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.
A version of this article appeared on Medscape.com.