ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The following clinically significant adverse reactions are also described elsewhere in the labeling:Serious Infusion-Related Reactions [see Warnings and Precautions (5.1) ]Neurotoxicity [see Warnings and Precautions (5.2)] Myocarditis [see Warnings and Precautions (5.3)] Hypertension [see Warnings and Precautions (5.4)] Orthostatic Hypotension [see Warnings and Precautions (5.5)] Serious Infusion-Related Reactions [see Warnings and Precautions (5.1) ]. Neurotoxicity [see Warnings and Precautions (5.2)] Myocarditis [see Warnings and Precautions (5.3)] Hypertension [see Warnings and Precautions (5.4)] Orthostatic Hypotension [see Warnings and Precautions (5.5)] The most common adverse reactions (>=25%) 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 (6.1). The most common Grade or laboratory abnormalities (>=5%) 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 (6.1). To report SUSPECTED ADVERSE REACTIONS, contact Y-mAbs Therapeutics, Inc, at 1-833-339-6227 (1-833-33YMABS), or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.. The most common adverse reactions (>=25%) 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 (6.1). The most common Grade or laboratory abnormalities (>=5%) 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 (6.1). 6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.The safety of DANYELZA in combination with GM-CSF was evaluated in patients with refractory or relapsed high-risk neuroblastoma in bone or bone marrow who had demonstrated partial response, minor response, or stable disease following initial or subsequent therapy, and in patients who were in second complete remission, from two open-label, single arm studies, Study 201 (n=25) and Study 12-230 (n=72). Patients received DANYELZA mg/kg/cycle administered as three separate intravenous infusions of mg/kg (Day 1, and 5) in the first week of each cycle. Patients also received GM-CSF 250 ug/m2/day subcutaneously on Days -4 to and GM-CSF 500 ug/m2/day subcutaneously on Days to [see Clinical Studies (14)]. The most common adverse reactions in Studies 201 and 12-230 (>=25% in either study) were 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. The most common Grade or laboratory abnormalities (>=5% in either study) 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. Study 201In Study 201, among 25 patients who received DANYELZA in combination with GM-CSF, 12% were exposed for months or longer and none were exposed for greater than one year. Serious adverse reactions occurred in 32% of patients who received DANYELZA in combination with GM-CSF. Serious adverse reactions in more than one patient included anaphylactic reaction (12%) and pain (8%). Permanent discontinuation of DANYELZA due to an adverse reaction occurred in 12% of patients. Adverse reactions resulting in permanent discontinuation of DANYELZA included anaphylactic reaction (8%) and respiratory depression (4%).Dosage interruptions of DANYELZA due to an adverse reaction occurred in 84% of patients. Adverse reactions requiring dosage interruption in 10% of patients included hypotension and bronchospasm.Table summarizes adverse reactions in Study 201.Table 4. Adverse Reactions (>10%) in Patients with Refractory or Relapsed High-Risk Neuroblastoma in Bone or Bone Marrow Who Received DANYELZA with GM-CSF in Study 201DANYELZA with GM-CSFAdverse reactions were graded using CTCAE version 4.0. (n=25)Adverse ReactionAll Grades (%)Grade or (%)Body systemGeneral disorders and administration site conditions PainPain includes pain, abdominal pain, pain in extremity, bone pain, neck pain, back pain, and musculoskeletal pain. 10072 Infusion-related reactionInfusion-related reaction includes hypotension, bronchospasm, flushing, wheezing, stridor, urticaria, dyspnea, pyrexia, infusion-related reaction, face edema, edema mouth, tongue edema, lip edema, respiratory tract edema, chills, hypoxia, pruritis and rash occurring on the day of infusion or the day following an infusion. 10068 Edema280 FatigueFatigue includes fatigue, asthenia. 280 PyrexiaPyrexia not occurring on the day of infusion or the day following an infusion 280Respiratory, thoracic and mediastinal disorders Cough600 Rhinorrhea240Vascular disorders Hypertension444Gastrointestinal disorders Vomiting604 Diarrhea568 Nausea560Skin and subcutaneous tissue disorders UrticariaUrticaria, not occurring on the day of infusion or the day following an infusion 324Cardiac disorders TachycardiaTachycardia includes sinus tachycardia and tachycardia 844Nervous system disorders Peripheral neuropathyPeripheral neuropathy includes peripheral sensory neuropathy, paresthesia, neuralgia. 320 Headache288 Depressed level of consciousness2416Eye disorders Neurological disorders of the eyeNeurological disorders of the eye includes unequal pupils, blurred vision, and mydriasis. 240Immune system disorders Anaphylactic reaction1212Metabolism and nutrition disorders Decreased appetite160Infections and infestations Influenza120 Rhinovirus infection120 Upper respiratory tract infection120Investigations Weight decreased120Psychiatric disorders Anxiety120Clinically relevant adverse reactions occurring in <=10% of patients who received DANYELZA with GM-CSF included peripheral edema (8%). Table summarizes the laboratory abnormalities in Study 201.Table 5. Selected Laboratory Abnormalities (>20%) Worsening from Baseline in Patients with Refractory or Relapsed High-Risk Neuroblastoma in Bone or Bone Marrow Who Received DANYELZA with GM-CSF in Study 201Laboratory AbnormalityDANYELZA with GM-CSFThe table presents laboratory parameters with available grading according to CTCAE version 4.0. Baseline evaluation was the last non-missing value prior to first DANYELZA dosing. Each test incidence is based on the number of patients who had both baseline value and at least one on-study laboratory measurement (range: 23 to 24 patients). n=25All Grades (%)Grade or (%)ChemistryDecreased potassium638Decreased albumin500Increased alanine aminotransferase428Decreased sodium290HematologyDecreased lymphocytes7430Decreased platelet count6517Decreased neutrophils6139Decreased hemoglobin484. Study 12-230In Study 12-230, among 72 patients who received DANYELZA in combination with GM-CSF, 32% were exposed for months or longer and 8% were exposed for greater than one year. Serious adverse reactions occurred in 40% of patients who received DANYELZA in combination with GM-CSF. Serious adverse reactions in 5% of patients included hypertension (14%), hypotension (11%), and pyrexia (8%). Permanent discontinuation of DANYELZA due to an adverse reaction occurred in 8% of patients. Four (6%) patients permanently discontinued DANYELZA due to hypertension and one (1.4%) patient discontinued due to RPLS. Table summarizes adverse reactions in Study 12-230.Table 6. Adverse Reactions (>10%) in Patients with Refractory or Relapsed High-Risk Neuroblastoma in Bone or Bone Marrow Who Received DANYELZA with GM-CSF in Study 12-230DANYELZA with GM-CSFIn Study 12-230, all adverse reactions occurring in Cycle and 2, and adverse reactions of >= Grade severity occurring in subsequent cycles were reported. In the dose finding phase, Grade unexpected adverse reactions were also reported for Cycles and later. Adverse reactions were graded using CTCAE version 4.0. (n=72)Adverse ReactionAll Grades (%)Grade or (%)Body systemGeneral disorders and administration site conditions Infusion-related reactionInfusion-related reaction includes hypotension, bronchospasm, flushing, wheezing, stridor, urticaria, dyspnea, pyrexia, face edema, periorbital edema, lip swelling, swollen tongue, chills, hypoxia, pruritis, rash maculopapular and rash erythematous occurring on the day of infusion or the day following an infusion. 9432 PainPain includes pain, abdominal pain, pain in extremity, bone pain, neck pain, back pain, non-cardiac chest pain, flank pain, and musculoskeletal pain. 942.8 FatigueFatigue includes fatigue, asthenia. 440 Injection site reaction280 Localized edema250 PyrexiaPyrexia not occurring on the day of infusion or the day following an infusion. 110Vascular disorders Hypertension287Gastrointestinal disorders Vomiting632.8 Nausea571.4 Diarrhea504.2 Constipation150Skin and subcutaneous tissue disorders Erythema multiforme330 Hyperhidrosis170 Erythema110Respiratory, thoracic and mediastinal disorders Cough570 Oropharyngeal pain150 Rhinorrhea150Nervous system disorders Peripheral neuropathyPeripheral neuropathy includes peripheral sensory neuropathy, peripheral motor neuropathy, paresthesia, neuralgia. 250 Headache180 Lethargy140Metabolism and nutrition disorders Decreased appetite534.2Cardiac disorders Sinus tachycardia441.4Psychiatric disorders Anxiety260 Irritability250Investigations Breath sounds abnormal150Injury and procedural complications Contusion150Infections and infestations Rhinovirus infection140 Enterovirus infection130Eye Disorders Neurological disorders of the eye Neurological disorders of the eye includes unequal pupils, blurred vision, accommodation disorder, visual impairment and photophobia. 190Clinically relevant adverse reactions in <=10% of patients who received DANYELZA with GM-CSF included apnea (4.2%), hypopnea (2.8%), generalized edema (2.8%), peripheral edema (8.3%), and device related infection (4.2%). Table summarizes the laboratory abnormalities in Study 12-230.Table 7. Selected Laboratory Abnormalities (>20%) Worsening from Baseline in Patients with Refractory or Relapsed High-Risk Neuroblastoma in Bone or Bone Marrow Who Received DANYELZA with GM-CSF in Study 12-230Laboratory AbnormalityDANYELZA with GM-CSFThe table presents laboratory parameters with available grading according to CTCAE version 4.0. Baseline evaluation was the last non-missing value prior to first DANYELZA dosing. Each test incidence is based on the number of patients who had both baseline value and at least one on-study laboratory measurement (range 19 to 72 patients). n=72All Grades (%)Grade or (%)Chemistry Increased glucose740 Decreased albumin687 Decreased calcium648 Increased alanine aminotransferase559 Decreased magnesium540 Increased aspartate aminotransferase494 Decreased phosphate475 Decreased potassium4732 Decreased sodium386 Decreased glucose298Hematology Decreased lymphocytes7956 Decreased hemoglobin7642 Decreased neutrophils7246 Decreased platelets7140. 6.2 Immunogenicity. As with all therapeutic proteins, there is potential for immunogenicity. The detection of anti-drug antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of anti-drug antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies or to other naxitamab products may be misleading.In Study 201, of 24 (8%) patients tested positive for anti-drug antibodies (ADA) after treatment with DANYELZA. In Study 12-230, 27 of 117 patients (23%) tested positive for ADA after treatment with DANYELZA by an assay that was not fully validated; therefore, the incidence of ADA may not be reliable.. 6.3 Postmarketing Experience/Spontaneous Reports. The following adverse reactions have been identified during expanded access and post-approval use of DANYELZA. Because these reactions are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.Neurological: Orthostatic hypotension, Transverse myelitisCardiac disorders: Myocarditis.

BOXED WARNING SECTION.

WARNING: SERIOUS INFUSION-RELATED REACTIONS and NEUROTOXICITY. WARNING: SERIOUS INFUSION-RELATED REACTIONS and NEUROTOXICITYSee full prescribing information for complete boxed warningSerious Infusion-Related Reactions: DANYELZA can cause serious infusion reactions, including cardiac arrest, anaphylaxis, hypotension, bronchospasm, and stridor. Premedicate prior to each DANYELZA infusion as recommended. Reduce the rate, interrupt infusion, or permanently discontinue DANYELZA based on severity 2.2, 2.3, 4, 5.1).Neurotoxicity: DANYELZA can cause severe neurotoxicity, including severe neuropathic pain, transverse myelitis, and reversible posterior leukoencephalopathy syndrome (RPLS). Premedicate to treat neuropathic pain as recommended. Permanently discontinue DANYELZA based on the adverse reaction and severity (2.2, 2.3, 5.2).. Serious Infusion-Related Reactions: DANYELZA can cause serious infusion reactions, including cardiac arrest, anaphylaxis, hypotension, bronchospasm, and stridor. Premedicate prior to each DANYELZA infusion as recommended. Reduce the rate, interrupt infusion, or permanently discontinue DANYELZA based on severity 2.2, 2.3, 4, 5.1).. Neurotoxicity: DANYELZA can cause severe neurotoxicity, including severe neuropathic pain, transverse myelitis, and reversible posterior leukoencephalopathy syndrome (RPLS). Premedicate to treat neuropathic pain as recommended. Permanently discontinue DANYELZA based on the adverse reaction and severity (2.2, 2.3, 5.2).. Serious Infusion-Related ReactionsDANYELZA can cause serious infusion reactions, including cardiac arrest, anaphylaxis, hypotension, bronchospasm, and stridor. Infusion reactions of any Grade occurred in 94-100% of patients. Severe infusion reactions occurred in 32-68% and serious infusion reactions occurred in - 18% of patients in DANYELZA clinical studies [see Warnings and Precautions (5.1)]. Premedicate prior to each DANYELZA infusion as recommended and monitor patients for at least hours following completion of each infusion. Reduce the rate, interrupt infusion, or permanently discontinue DANYELZA based on severity [see Dosage and Administration (2.2, 2.3), Contraindications (4), and Warnings and Precautions (5.1)]. DANYELZA can cause serious infusion reactions, including cardiac arrest, anaphylaxis, hypotension, bronchospasm, and stridor. Infusion reactions of any Grade occurred in 94-100% of patients. Severe infusion reactions occurred in 32-68% and serious infusion reactions occurred in - 18% of patients in DANYELZA clinical studies [see Warnings and Precautions (5.1)]. Premedicate prior to each DANYELZA infusion as recommended and monitor patients for at least hours following completion of each infusion. Reduce the rate, interrupt infusion, or permanently discontinue DANYELZA based on severity [see Dosage and Administration (2.2, 2.3), Contraindications (4), and Warnings and Precautions (5.1)]. NeurotoxicityDANYELZA can cause severe neurotoxicity, including severe neuropathic pain, transverse myelitis and reversible posterior leukoencephalopathy syndrome (RPLS). Pain of any Grade occurred in 94-100% of patients in DANYELZA clinical studies [see Warnings and Precautions (5.2)]. Premedicate to treat neuropathic pain as recommended. Permanently discontinue DANYELZA based on the adverse reaction and severity [see Dosage and Administration (2.2, 2.3) and Warnings and Precautions (5.2)]. DANYELZA can cause severe neurotoxicity, including severe neuropathic pain, transverse myelitis and reversible posterior leukoencephalopathy syndrome (RPLS). Pain of any Grade occurred in 94-100% of patients in DANYELZA clinical studies [see Warnings and Precautions (5.2)]. Premedicate to treat neuropathic pain as recommended. Permanently discontinue DANYELZA based on the adverse reaction and severity [see Dosage and Administration (2.2, 2.3) and Warnings and Precautions (5.2)].

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. The efficacy of DANYELZA in combination with GM-CSF was evaluated in two open-label, single arm trials in patients with high-risk neuroblastoma with refractory or relapsed disease in the bone or bone marrow, Study 201 and Study 12-230. Study 201The efficacy of DANYELZA in combination with GM-CSF was evaluated in Study 201 (NCT03363373), multicenter open-label, single arm trial, in subpopulation of patients who had refractory or relapsed high-risk neuroblastoma in the bone or bone marrow and demonstrated partial response, minor response, or stable disease to prior therapy. Patients with progressive disease were excluded. All patients received at least one systemic therapy to treat disease outside of the bone or bone marrow prior to enrollment. Patients received DANYELZA mg/kg/cycle administered as three separate intravenous infusions of mg/kg on Days 1, and of each cycle. Patients received GM-CSF subcutaneously at 250 ug/m2/day on Days -4 to and at 500 ug/m2/day on Days to 5. Preplanned radiation to the primary site was allowed.The major efficacy outcome measure was overall response rate (ORR) according to the revised International Neuroblastoma Response Criteria (INRC), as determined by independent pathology and imaging review and confirmed by at least one subsequent assessment. An additional efficacy outcome measure was duration of response (DOR). Of the 22 patients included in the efficacy analysis, 64% had refractory disease and 36% had relapsed disease; the median age was years (range to 10 years), 59% were male; 45% were White, 50% were Asian and 5% were Black. MYCN amplification was present in 14% of patients and 86% of patients were International Neuroblastoma Staging System (INSS) stage at time of diagnosis. Disease sites included 59% in the bone only, 9% in bone marrow only, and 32% in both. Prior therapies included surgery (91%), chemotherapy (95%), radiation (36%), autologous stem cell transplant (ASCT) (18%), and anti-GD2 antibody treatment (18%).Efficacy results for Study 201 are described in Table 8. Table 8. Efficacy Results from Study 201DANYELZA with GM-CSF (n=22)CI confidence interval NE: not estimable.Overall response rateOverall response rate is defined as complete or partial response according to the revised INRC (2017) that was confirmed by at least one subsequent assessment. Responses were observed in the bone, bone marrow, or both bone and bone marrow. (95% CI)45% (24%, 68%) Complete response rate36% Partial response rate9%Duration of response Median (95% CI), months6.2 (4.9, NE) Responders with DOR >= months30%In an exploratory analysis in the subset of patients previously treated with an anti-GD2 antibody (n=4), one patient demonstrated confirmed complete response and no patients demonstrated partial response. Study 12-230The efficacy of DANYELZA in combination with GM-CSF was evaluated in Study 12-230 (NCT01757626), single center, open-label, single arm trial, in subpopulation of patients who had relapsed or refractory high-risk neuroblastoma in bone or bone marrow and demonstrated partial response, minor response, or stable disease to prior therapy. Patients with progressive disease were excluded. All patients received at least one systemic therapy to treat disease outside of the bone or bone marrow prior to enrollment. Patients were required to have received at least one dose of DANYELZA at dose of mg/kg or greater per infusion and have evaluable disease at baseline according to independent review per the revised INRC. Patients received DANYELZA mg/kg/cycle administered as three separate intravenous infusions of mg/kg (on Days 1, and 5) in the first week of each cycle. Patients received GM-CSF subcutaneously at 250 ug/m2/day on Days -4 to and at 500 ug/m2/day on Days to 5. Radiation to non-target bony lesions and soft tissue lesions was permitted at the investigators discretion; assessment of response excluded sites that received radiation. The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR), as determined by independent pathology and imaging review according to the revised INRC and confirmed by at least one subsequent assessment. Of the 38 patients included in the efficacy analysis, 55% had relapsed neuroblastoma and 45% had refractory disease; 50% were male, the median age was years (range to 23 years), 74% were White, 8% Asian and 5% were Black, 5% Native American/American Indian/Alaska Native, 3% other races and 5% was not available. MYCN-amplification was present in 16% of patients and most patients were International Neuroblastoma Staging System (INSS) stage (95%). Fifty percent (50%) of patients had disease involvement in the bone only, 11% only in bone marrow, and 39% in both. Prior therapies included surgery (100%), chemotherapy (100%), radiation (47%), autologous stem cell transplant (ASCT) (42%), and anti-GD2 antibody treatment (58%). Efficacy results are provided in Table 9. Table 9. Efficacy Results from Study 12-230DANYELZA with GM-CSF (n=38)CI confidence intervalOverall response rateOverall response rate is defined as complete or partial response according to the revised INRC (2017) that was confirmed by at least one subsequent assessment. Responses were observed in the bone, bone marrow, or both bone and bone marrow. (95% CI)34% (20%, 51%) Complete response rate26% Partial response rate8%Duration of Response Responders with DOR >= months23%In an exploratory analysis in the subset of patients previously treated with an anti-GD2 antibody (n=22), the ORR was 18% (95% CI 5%, 40%), with no patients having documented response of months or greater.

CLINICAL TRIALS EXPERIENCE SECTION.

6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.The safety of DANYELZA in combination with GM-CSF was evaluated in patients with refractory or relapsed high-risk neuroblastoma in bone or bone marrow who had demonstrated partial response, minor response, or stable disease following initial or subsequent therapy, and in patients who were in second complete remission, from two open-label, single arm studies, Study 201 (n=25) and Study 12-230 (n=72). Patients received DANYELZA mg/kg/cycle administered as three separate intravenous infusions of mg/kg (Day 1, and 5) in the first week of each cycle. Patients also received GM-CSF 250 ug/m2/day subcutaneously on Days -4 to and GM-CSF 500 ug/m2/day subcutaneously on Days to [see Clinical Studies (14)]. The most common adverse reactions in Studies 201 and 12-230 (>=25% in either study) were 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. The most common Grade or laboratory abnormalities (>=5% in either study) 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. Study 201In Study 201, among 25 patients who received DANYELZA in combination with GM-CSF, 12% were exposed for months or longer and none were exposed for greater than one year. Serious adverse reactions occurred in 32% of patients who received DANYELZA in combination with GM-CSF. Serious adverse reactions in more than one patient included anaphylactic reaction (12%) and pain (8%). Permanent discontinuation of DANYELZA due to an adverse reaction occurred in 12% of patients. Adverse reactions resulting in permanent discontinuation of DANYELZA included anaphylactic reaction (8%) and respiratory depression (4%).Dosage interruptions of DANYELZA due to an adverse reaction occurred in 84% of patients. Adverse reactions requiring dosage interruption in 10% of patients included hypotension and bronchospasm.Table summarizes adverse reactions in Study 201.Table 4. Adverse Reactions (>10%) in Patients with Refractory or Relapsed High-Risk Neuroblastoma in Bone or Bone Marrow Who Received DANYELZA with GM-CSF in Study 201DANYELZA with GM-CSFAdverse reactions were graded using CTCAE version 4.0. (n=25)Adverse ReactionAll Grades (%)Grade or (%)Body systemGeneral disorders and administration site conditions PainPain includes pain, abdominal pain, pain in extremity, bone pain, neck pain, back pain, and musculoskeletal pain. 10072 Infusion-related reactionInfusion-related reaction includes hypotension, bronchospasm, flushing, wheezing, stridor, urticaria, dyspnea, pyrexia, infusion-related reaction, face edema, edema mouth, tongue edema, lip edema, respiratory tract edema, chills, hypoxia, pruritis and rash occurring on the day of infusion or the day following an infusion. 10068 Edema280 FatigueFatigue includes fatigue, asthenia. 280 PyrexiaPyrexia not occurring on the day of infusion or the day following an infusion 280Respiratory, thoracic and mediastinal disorders Cough600 Rhinorrhea240Vascular disorders Hypertension444Gastrointestinal disorders Vomiting604 Diarrhea568 Nausea560Skin and subcutaneous tissue disorders UrticariaUrticaria, not occurring on the day of infusion or the day following an infusion 324Cardiac disorders TachycardiaTachycardia includes sinus tachycardia and tachycardia 844Nervous system disorders Peripheral neuropathyPeripheral neuropathy includes peripheral sensory neuropathy, paresthesia, neuralgia. 320 Headache288 Depressed level of consciousness2416Eye disorders Neurological disorders of the eyeNeurological disorders of the eye includes unequal pupils, blurred vision, and mydriasis. 240Immune system disorders Anaphylactic reaction1212Metabolism and nutrition disorders Decreased appetite160Infections and infestations Influenza120 Rhinovirus infection120 Upper respiratory tract infection120Investigations Weight decreased120Psychiatric disorders Anxiety120Clinically relevant adverse reactions occurring in <=10% of patients who received DANYELZA with GM-CSF included peripheral edema (8%). Table summarizes the laboratory abnormalities in Study 201.Table 5. Selected Laboratory Abnormalities (>20%) Worsening from Baseline in Patients with Refractory or Relapsed High-Risk Neuroblastoma in Bone or Bone Marrow Who Received DANYELZA with GM-CSF in Study 201Laboratory AbnormalityDANYELZA with GM-CSFThe table presents laboratory parameters with available grading according to CTCAE version 4.0. Baseline evaluation was the last non-missing value prior to first DANYELZA dosing. Each test incidence is based on the number of patients who had both baseline value and at least one on-study laboratory measurement (range: 23 to 24 patients). n=25All Grades (%)Grade or (%)ChemistryDecreased potassium638Decreased albumin500Increased alanine aminotransferase428Decreased sodium290HematologyDecreased lymphocytes7430Decreased platelet count6517Decreased neutrophils6139Decreased hemoglobin484. Study 12-230In Study 12-230, among 72 patients who received DANYELZA in combination with GM-CSF, 32% were exposed for months or longer and 8% were exposed for greater than one year. Serious adverse reactions occurred in 40% of patients who received DANYELZA in combination with GM-CSF. Serious adverse reactions in 5% of patients included hypertension (14%), hypotension (11%), and pyrexia (8%). Permanent discontinuation of DANYELZA due to an adverse reaction occurred in 8% of patients. Four (6%) patients permanently discontinued DANYELZA due to hypertension and one (1.4%) patient discontinued due to RPLS. Table summarizes adverse reactions in Study 12-230.Table 6. Adverse Reactions (>10%) in Patients with Refractory or Relapsed High-Risk Neuroblastoma in Bone or Bone Marrow Who Received DANYELZA with GM-CSF in Study 12-230DANYELZA with GM-CSFIn Study 12-230, all adverse reactions occurring in Cycle and 2, and adverse reactions of >= Grade severity occurring in subsequent cycles were reported. In the dose finding phase, Grade unexpected adverse reactions were also reported for Cycles and later. Adverse reactions were graded using CTCAE version 4.0. (n=72)Adverse ReactionAll Grades (%)Grade or (%)Body systemGeneral disorders and administration site conditions Infusion-related reactionInfusion-related reaction includes hypotension, bronchospasm, flushing, wheezing, stridor, urticaria, dyspnea, pyrexia, face edema, periorbital edema, lip swelling, swollen tongue, chills, hypoxia, pruritis, rash maculopapular and rash erythematous occurring on the day of infusion or the day following an infusion. 9432 PainPain includes pain, abdominal pain, pain in extremity, bone pain, neck pain, back pain, non-cardiac chest pain, flank pain, and musculoskeletal pain. 942.8 FatigueFatigue includes fatigue, asthenia. 440 Injection site reaction280 Localized edema250 PyrexiaPyrexia not occurring on the day of infusion or the day following an infusion. 110Vascular disorders Hypertension287Gastrointestinal disorders Vomiting632.8 Nausea571.4 Diarrhea504.2 Constipation150Skin and subcutaneous tissue disorders Erythema multiforme330 Hyperhidrosis170 Erythema110Respiratory, thoracic and mediastinal disorders Cough570 Oropharyngeal pain150 Rhinorrhea150Nervous system disorders Peripheral neuropathyPeripheral neuropathy includes peripheral sensory neuropathy, peripheral motor neuropathy, paresthesia, neuralgia. 250 Headache180 Lethargy140Metabolism and nutrition disorders Decreased appetite534.2Cardiac disorders Sinus tachycardia441.4Psychiatric disorders Anxiety260 Irritability250Investigations Breath sounds abnormal150Injury and procedural complications Contusion150Infections and infestations Rhinovirus infection140 Enterovirus infection130Eye Disorders Neurological disorders of the eye Neurological disorders of the eye includes unequal pupils, blurred vision, accommodation disorder, visual impairment and photophobia. 190Clinically relevant adverse reactions in <=10% of patients who received DANYELZA with GM-CSF included apnea (4.2%), hypopnea (2.8%), generalized edema (2.8%), peripheral edema (8.3%), and device related infection (4.2%). Table summarizes the laboratory abnormalities in Study 12-230.Table 7. Selected Laboratory Abnormalities (>20%) Worsening from Baseline in Patients with Refractory or Relapsed High-Risk Neuroblastoma in Bone or Bone Marrow Who Received DANYELZA with GM-CSF in Study 12-230Laboratory AbnormalityDANYELZA with GM-CSFThe table presents laboratory parameters with available grading according to CTCAE version 4.0. Baseline evaluation was the last non-missing value prior to first DANYELZA dosing. Each test incidence is based on the number of patients who had both baseline value and at least one on-study laboratory measurement (range 19 to 72 patients). n=72All Grades (%)Grade or (%)Chemistry Increased glucose740 Decreased albumin687 Decreased calcium648 Increased alanine aminotransferase559 Decreased magnesium540 Increased aspartate aminotransferase494 Decreased phosphate475 Decreased potassium4732 Decreased sodium386 Decreased glucose298Hematology Decreased lymphocytes7956 Decreased hemoglobin7642 Decreased neutrophils7246 Decreased platelets7140.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. The recommended dosage of DANYELZA is mg/kg/day (up to 150 mg/day), administered as an intravenous infusion after dilution on Days 1, 3, and of each treatment cycle. Treatment cycles are repeated every weeks until complete response or partial response, followed by additional cycles every weeks. Subsequent cycles may be repeated every weeks. Discontinue DANYELZA and GM-CSF for disease progression or unacceptable toxicity. Administer GM-CSF subcutaneously prior to and during each treatment cycle as recommended. (2.1). 2.1 Recommended Dosage. The recommended dosage of DANYELZA is mg/kg/day (up to 150 mg/day) on Days 1, 3, and of each treatment cycle, administered as an intravenous infusion after dilution [see Dosage and Administration (2.4 and 2.5)] 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 weeks until complete response or partial response, followed by additional cycles every weeks. Subsequent cycles may be repeated every weeks. Discontinue DANYELZA and GM-CSF for disease progression or unacceptable toxicity.Administer pre-infusion medications and supportive treatment, as appropriate, during infusion. [see Dosage and Administration (2.2)] The recommended dosage regimen for each treatment cycle is described below and in Table 1: Days -4 to 0: administer GM-CSF 250 ug/m2/day by subcutaneous injection, beginning days prior to DANYELZA infusion.Days to 5: administer GM-CSF 500 ug/m2/day by subcutaneous injection. Administer at least hour prior to DANYELZA administration on Days 1, 3, and 5.Days, 1, 3, and 5: administer DANYELZA mg/kg/day (up to 150 mg/day) by intravenous infusion.Table Dose and Schedule of GM-CSF and DANYELZA Within One Treatment CycleDay-4-3-2-1012345Subcutaneous GM-CSF250 ug/m2/day500 ug/m2/dayIntravenous DANYELZA3 mg/kg/day3 mg/kg/day3 mg/kg/day. Days -4 to 0: administer GM-CSF 250 ug/m2/day by subcutaneous injection, beginning days prior to DANYELZA infusion.. Days to 5: administer GM-CSF 500 ug/m2/day by subcutaneous injection. Administer at least hour prior to DANYELZA administration on Days 1, 3, and 5.. Days, 1, 3, and 5: administer DANYELZA mg/kg/day (up to 150 mg/day) by intravenous infusion.. Missed DoseIf DANYELZA dose is missed, administer the missed dose the following week by Day 10. Administer GM-CSF 500 ug /m2/day on the first day of the DANYELZA infusion, and on the day before and on the day of the second and third infusion, respectively (i.e. total of days with 500 ug /m2/day).. 2.2 Premedications and Supportive Medications Pain Management Prior to and During Infusion [see Warnings and Precautions (5.2)]:Five days prior to the first infusion of DANYELZA in each cycle, initiate 12-day course (Day -4 through Day 7) of prophylactic medication for neuropathic pain, such as gabapentin.Administer oral opioids 45-60 minutes prior to initiation of each DANYELZA infusion and additional intravenous opioids as needed for breakthrough pain during the infusion. Consider use of ketamine for pain that is not adequately controlled by opioids.. Five days prior to the first infusion of DANYELZA in each cycle, initiate 12-day course (Day -4 through Day 7) of prophylactic medication for neuropathic pain, such as gabapentin.. Administer oral opioids 45-60 minutes prior to initiation of each DANYELZA infusion and additional intravenous opioids as needed for breakthrough pain during the infusion. Consider use of ketamine for pain that is not adequately controlled by opioids.. Premedication: Reduce Risk of Infusion-Related Reactions and Nausea/Vomiting [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)].Administer intravenous corticosteroids (e.g. methylprednisolone mg/kg with maximum dose of 80 mg or equivalent corticosteroid dose) 30 minutes to hours prior to the first infusion of DANYELZA. Administer corticosteroid premedication for subsequent infusions if severe infusion reaction occurred with the previous infusion or during the previous cycle. Administer an antihistamine, an H2 antagonist, acetaminophen and an antiemetic 30 minutes prior to each infusion. Administer intravenous corticosteroids (e.g. methylprednisolone mg/kg with maximum dose of 80 mg or equivalent corticosteroid dose) 30 minutes to hours prior to the first infusion of DANYELZA. Administer corticosteroid premedication for subsequent infusions if severe infusion reaction occurred with the previous infusion or during the previous cycle. Administer an antihistamine, an H2 antagonist, acetaminophen and an antiemetic 30 minutes prior to each infusion. 2.3 Dosage Modifications for Adverse Reactions The recommended dosage modifications for DANYELZA for adverse reactions are presented in Table 2. Table 2. Recommended DANYELZA Dosage Modifications for Adverse ReactionsAdverse ReactionSeverityBased on Common Terminology Criteria for Adverse Events (CTCAE) 5.0 Dosage ModificationsInfusion-related reactions [see Warnings and Precautions (5.1)] Grade 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 hoursReduce DANYELZA 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 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 sequelaeImmediately interrupt DANYELZA 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 DANYELZA in patients not responding to medical intervention.Grade infusion-related reactions Defined as:Life-threatening consequences: urgent intervention indicatedorGrade or anaphylaxisPermanently discontinue DANYELZA.Pain [see Warnings and Precautions (5.2)] Grade unresponsive to maximum supportive measuresPermanently discontinue DANYELZA.Reversible posterior leukoencephalopathy syndrome (RPLS) [see Warnings and Precautions (5.2)] All GradesPermanently discontinue DANYELZA.Transverse myelitis [see Warnings and Precautions (5.2)] All GradesPermanently discontinue DANYELZA.Peripheral neuropathy [see Warnings and Precautions (5.2)] Motor neuropathy: Grade or greater orSensory neuropathy: Grade or 4Permanently discontinue DANYELZA.Neurological disorders of the eye [see Warnings and Precautions (5.2)] Grade to resulting in decreased visual acuity or limiting activities of daily livingWithhold DANYELZA until resolution.If resolved resume DANYELZA at 50% of the prior dose; if tolerated without recurrence of symptoms, gradually increase DANYELZA to dose prior to onset of symptoms.Permanently discontinue DANYELZA if not resolved within weeks or upon recurrence.Subtotal or total vision lossPermanently discontinue DANYELZA.Prolonged urinary retention [see Warnings and Precautions (5.2)] Persisting following discontinuation of opioidsPermanently discontinue DANYELZA.Myocarditis [see Warnings and Precautions (5.3)] Grade or 3Withhold, reduce dose, or permanently discontinue DANYELZA treatment based on severity and duration.Grade 4Permanently discontinue DANYELZA.Hypertension [see Warnings and Precautions (5.4)] Grade 3Withhold DANYELZA or pause infusion until recovery to <= Grade 2.Resume infusion at 50% of prior rate; if tolerated without recurrence of symptoms, gradually increase DANYELZA to rate prior to onset of symptoms.Permanently discontinue DANYELZA in patients not responding to medical intervention.Grade 4Permanently discontinue DANYELZA.Orthostatic hypotension [see Warnings and precautions (5.5)] All gradesWithhold DANYELZA until recovery to Grade <= 1.If resolved within week, restart DANYELZA at 50% of the prior dose; if tolerated without recurrence of symptoms after completion of next cycle, resume to recommended dose for subsequent cycles.If not resolved within week, permanently discontinue DANYELZA.Other Adverse Reactions [see Adverse Reactions (6.1)] Grade 3Withhold DANYELZA until recovery to Grade <= 2.If resolved to Grade <= resume DANYELZA at same rate.Permanently discontinue DANYELZA if not resolved to Grade <=2 within weeks.Grade 4Permanently discontinue DANYELZA.. Reduce DANYELZA 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.. Immediately interrupt DANYELZA 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 DANYELZA in patients not responding to medical intervention.. Permanently discontinue DANYELZA.. Permanently discontinue DANYELZA.. Permanently discontinue DANYELZA.. Permanently discontinue DANYELZA.. Permanently discontinue DANYELZA.. Withhold DANYELZA until resolution.. If resolved resume DANYELZA at 50% of the prior dose; if tolerated without recurrence of symptoms, gradually increase DANYELZA to dose prior to onset of symptoms.. Permanently discontinue DANYELZA if not resolved within weeks or upon recurrence.. Permanently discontinue DANYELZA.. Permanently discontinue DANYELZA.. Withhold, reduce dose, or permanently discontinue DANYELZA treatment based on severity and duration.. Permanently discontinue DANYELZA.. Withhold DANYELZA or pause infusion until recovery to <= Grade 2.. Resume infusion at 50% of prior rate; if tolerated without recurrence of symptoms, gradually increase DANYELZA to rate prior to onset of symptoms.. Permanently discontinue DANYELZA in patients not responding to medical intervention.. Permanently discontinue DANYELZA.. Withhold DANYELZA until recovery to Grade <= 1.. If resolved within week, restart DANYELZA at 50% of the prior dose; if tolerated without recurrence of symptoms after completion of next cycle, resume to recommended dose for subsequent cycles.. If not resolved within week, permanently discontinue DANYELZA.. Withhold DANYELZA until recovery to Grade <= 2.. If resolved to Grade <= resume DANYELZA at same rate.. Permanently discontinue DANYELZA if not resolved to Grade <=2 within weeks.. Permanently discontinue DANYELZA.. 2.4 Preparation Use appropriate aseptic technique.Visually inspect vial for particulate matter and discoloration prior to administration. Discard vial if solution is discolored, cloudy, or contains particulate matter.Add appropriate quantities of 5% Albumin (Human), USP and 0.9% Sodium Chloride Injection, USP to an empty, sterile intravenous infusion bag large enough to hold the volume needed for the relevant dose as indicated in Table 3. Allow for 5-10 minutes of passive mixing.Withdraw the required dose of DANYELZA and inject into the infusion bag containing the 5% Albumin (Human), USP and 0.9% Sodium Chloride Injection, USP. Discard any unused portion of DANYELZA left in the vial.Preparation instructions for DANYELZA are described in Table 3.Table 3. Preparation of DANYELZA, mg/mLDANYELZA dose (mg)DANYELZA volume (mL)Volume of 5% Albumin (Human), USP (mL)Total infusion volume achieved by adding sufficient 0.9% Sodium Chloride Injection, USP (mL)Final concentration of prepared DANYELZA infusion (mg/mL)<= 80<= 201050<= 1.681 to 120> 20 to 3015751.1 to 1.6121 to 150> 30 to 37.5201001.2 to 1.5If not used immediately, store the diluted DANYELZA infusion solution at room temperature (15C to 25C [59oF to 77oF]) for up to hours or refrigerate (2C to 8C [36F to 46F]) for up to 24 hours. Once removed from refrigeration, initiate infusion within hours.. Use appropriate aseptic technique.. Visually inspect vial for particulate matter and discoloration prior to administration. Discard vial if solution is discolored, cloudy, or contains particulate matter.. Add appropriate quantities of 5% Albumin (Human), USP and 0.9% Sodium Chloride Injection, USP to an empty, sterile intravenous infusion bag large enough to hold the volume needed for the relevant dose as indicated in Table 3. Allow for 5-10 minutes of passive mixing.. Withdraw the required dose of DANYELZA and inject into the infusion bag containing the 5% Albumin (Human), USP and 0.9% Sodium Chloride Injection, USP. Discard any unused portion of DANYELZA left in the vial.. 2.5 Administration. Administer DANYELZA as diluted intravenous infusion as recommended. Do not administer DANYELZA as an intravenous push or bolus [see Dosage and Administration (2.4)].For the first infusion (Cycle 1, Day 1), administer DANYELZA intravenously over 60 minutes. For subsequent infusions, administer DANYELZA intravenously over 30 to 60 minutes, as tolerated. [see Dosage and Administration (2.1, 2.3)]. Observe patients for minimum of hours following each infusion.. Administer DANYELZA as diluted intravenous infusion as recommended. Do not administer DANYELZA as an intravenous push or bolus [see Dosage and Administration (2.4)].. For the first infusion (Cycle 1, Day 1), administer DANYELZA intravenously over 60 minutes. For subsequent infusions, administer DANYELZA intravenously over 30 to 60 minutes, as tolerated. [see Dosage and Administration (2.1, 2.3)]. Observe patients for minimum of hours following each infusion.

SPL PATIENT PACKAGE INSERT SECTION.

This Patient Information has been approved by the U.S. Food and Drug AdministrationRevised: 08/2025 PATIENT INFORMATION DANYELZA(R) (dan-YEL-zah) (naxitamab-gqgk) injection, for intravenous use What is the most important information should know about DANYELZA DANYELZA may cause serious side effects, including:Serious infusion-related reactions. DANYELZA can cause serious infusion-related reactions that require immediate medical attention. Infusion-related reactions are common with DANYELZA. Tell your healthcare provider right away if you get any signs or symptoms during or after your DANYELZA infusion, including:swelling of your face, eyes, lips, mouth, or tongueitchingredness on your face (flushing)skin rash or hives trouble breathing cough or wheezingnoisy high-pitched breathingfeeling faint or dizziness (low blood pressure) Nervous system problems. Talk to your healthcare provider right away if you have new symptoms or worsening of nervous system problems, including: Severe pain from nerves (neuropathic pain), including pain in the belly (abdomen), bone, neck, legs or arms. Pain is common with DANYELZA and can be severe. Inflammation of the spinal cord. Signs or symptoms may include:weakness in your legs or arms bladder and bowel problemspain in back, legs, or stomach (abdomen)numbnesstinglingburning sensationReversible Posterior Leukoencephalopathy Syndrome (RPLS also known as Posterior Reversible Encephalopathy Syndrome PRES). PRES is condition that affects the brain. Your healthcare provider will monitor your blood pressure and check for any neurologic symptoms after your DANYELZA infusion. Signs or symptoms of PRES may include: severe headache vision changeschanges in mental status, such as confusion, disorientation, or decreased alertnessdifficulty speakingweakness in your arms or legsseizuresNumbness, tingling, or burning sensation in the arms or legs. Nervous system problems of the eye. Signs or symptoms may include:unequal pupil size blurred visiontrouble focusing your eyeslarger pupil size (dilated) decreased ability to seesensitivity to lightProblems urinating or emptying your bladder (prolonged urinary retention). What is DANYELZA DANYELZA is prescription medicine used in combination with medicine called granulocyte-macrophage colony-stimulating factor (GM-CSF) to treat children year of age and older and adults with high-risk neuroblastoma in the bone or bone marrow that: has come back (relapsed) or that did not respond to previous treatment (refractory), and has shown partial response, minor response, or stable disease to prior therapy. It is not known if DANYELZA is safe and effective in children younger than year of age. Do not receive DANYELZA if you have had severe allergic reaction to naxitamab-gqgk, the active ingredient in DANYELZA. Ask your healthcare provider if you are not sure. Before receiving DANYELZA, tell your healthcare provider about all your medical conditions, including if you:have high blood pressurehave heart disease are pregnant or plan to become pregnant. DANYELZA may harm your unborn baby. Your healthcare provider will do pregnancy test before you start treatment with DANYELZA. Females who are able to become pregnant should use effective birth control (contraception) during treatment and for months after your last dose of DANYELZA. Talk to your healthcare provider about birth control choices that may be right for you during this time. Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with DANYELZA.are breastfeeding or plan to breastfeed. It is not known if DANYELZA passes into your breast milk. Do not breastfeed during treatment and for months after your last dose of DANYELZA.Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. How will receive DANYELZAYour healthcare provider will give you DANYELZA into your vein through an intravenous (I.V.) line over 30 or 60 minutes.DANYELZA is given on Days 1, 3, and of each treatment cycle. DANYELZA is used with another medicine called GM-CSF. You can ask your healthcare provider for information about GM-CSF.DANYELZA treatment cycles are usually repeated every or weeks. Your healthcare provider will decide how many treatment cycles you need.Your healthcare provider will give you certain medicines before and during your DANYELZA infusion to help decrease your risk of getting pain, infusion-related reactions, and nausea or vomiting.Your healthcare provider may slow down your infusion rate, temporarily stop DANYELZA infusion, or permanently stop treatment with DANYELZA if you have certain side effects. You will be monitored for side effects for at least hours after each DANYELZA infusion.If you miss an appointment, call your healthcare provider as soon as possible to reschedule. What are the possible side effects of DANYELZA DANYELZA may cause serious side effects, including:See What is the most important information should know about DANYELZASwelling of the heart (myocarditis). Myocarditis has happened in adolescents ages 12 to 18 within days of receiving DANYELZA. Tell your healthcare provider if you get any signs or symptoms of myocarditis, including:chest painshortness of breath irregular heartbeat or feel like your heart is racingHigh blood pressure (hypertension). High blood pressure is common in people who receive DANYELZA. Your blood pressure will be monitored during your DANYELZA infusion, and at least each day on Days to of each DANYELZA treatment cycle. Tell your healthcare provider right away if you get any signs or symptoms of high blood pressure, including:headachesseizuresnausea or vomitingchest paindizzinessvisual changesshortness of breathfeeling that your heart is pounding or racing (palpitations)nose bleedsDecreased blood pressure (orthostatic hypotension) that can be severe and require hospitalization. You may feel dizzy, lightheaded, or pass out (faint) when you rise too quickly from sitting or lying position. Your healthcare provider will monitor your blood pressure before you start and during treatment with DANYELZA. The most common side effects of DANYELZA include:fast heart ratevomiting coughnauseadecreased white blood cell, red blood cell, and platelet countsdiarrheadecreased appetitetirednessskin rashesdecreased level of potassium, sodium, and phosphate in the bloodhives feverheadacheinjection site reactionswelling of the body or only in one part of the bodyanxietyirritabilityincreased liver function blood testsdecreased blood sugar leveldecreased calcium levels in the blood decreased protein levels (albumin) in the bloodThese are not all of the possible side effects of DANYELZA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. General information about the safe and effective use of DANYELZA. Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflet. You can ask your pharmacist or healthcare provider for information about DANYELZA that is written for health professionals. What are the ingredients in DANYELZAActive ingredient: naxitamab-gqgk Inactive ingredients: citric acid anhydrous, poloxamer 188, sodium chloride, sodium citrate, Water for Injection. Manufactured by: Y-mAbs Therapeutics, Inc., 202 Carnegie Center, Suite 301, Princeton, NJ 08540 U.S. License number 2209 For more information, go to www.DANYELZA.com or call 1-833-339-6227 (1-833-33YMABS) Serious infusion-related reactions. DANYELZA can cause serious infusion-related reactions that require immediate medical attention. Infusion-related reactions are common with DANYELZA. Tell your healthcare provider right away if you get any signs or symptoms during or after your DANYELZA infusion, including:. swelling of your face, eyes, lips, mouth, or tongue. itching. redness on your face (flushing). skin rash or hives trouble breathing cough or wheezing. noisy high-pitched breathing. feeling faint or dizziness (low blood pressure) Nervous system problems. Talk to your healthcare provider right away if you have new symptoms or worsening of nervous system problems, including: Severe pain from nerves (neuropathic pain), including pain in the belly (abdomen), bone, neck, legs or arms. Pain is common with DANYELZA and can be severe. Inflammation of the spinal cord. Signs or symptoms may include:. weakness in your legs or arms bladder and bowel problems. pain in back, legs, or stomach (abdomen). numbness. tingling. burning sensation. Reversible Posterior Leukoencephalopathy Syndrome (RPLS also known as Posterior Reversible Encephalopathy Syndrome PRES). PRES is condition that affects the brain. Your healthcare provider will monitor your blood pressure and check for any neurologic symptoms after your DANYELZA infusion. Signs or symptoms of PRES may include: severe headache vision changes. changes in mental status, such as confusion, disorientation, or decreased alertness. difficulty speaking. weakness in your arms or legs. seizures. Numbness, tingling, or burning sensation in the arms or legs. Nervous system problems of the eye. Signs or symptoms may include:. unequal pupil size blurred vision. trouble focusing your eyes. larger pupil size (dilated) decreased ability to see. sensitivity to light. Problems urinating or emptying your bladder (prolonged urinary retention). has come back (relapsed) or that did not respond to previous treatment (refractory), and has shown partial response, minor response, or stable disease to prior therapy.. have high blood pressure. have heart disease are pregnant or plan to become pregnant. DANYELZA may harm your unborn baby. Your healthcare provider will do pregnancy test before you start treatment with DANYELZA. Females who are able to become pregnant should use effective birth control (contraception) during treatment and for months after your last dose of DANYELZA. Talk to your healthcare provider about birth control choices that may be right for you during this time. Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with DANYELZA.. are breastfeeding or plan to breastfeed. It is not known if DANYELZA passes into your breast milk. Do not breastfeed during treatment and for months after your last dose of DANYELZA.. Your healthcare provider will give you DANYELZA into your vein through an intravenous (I.V.) line over 30 or 60 minutes.. DANYELZA is given on Days 1, 3, and of each treatment cycle. DANYELZA is used with another medicine called GM-CSF. You can ask your healthcare provider for information about GM-CSF.. DANYELZA treatment cycles are usually repeated every or weeks. Your healthcare provider will decide how many treatment cycles you need.. Your healthcare provider will give you certain medicines before and during your DANYELZA infusion to help decrease your risk of getting pain, infusion-related reactions, and nausea or vomiting.. Your healthcare provider may slow down your infusion rate, temporarily stop DANYELZA infusion, or permanently stop treatment with DANYELZA if you have certain side effects. You will be monitored for side effects for at least hours after each DANYELZA infusion.. If you miss an appointment, call your healthcare provider as soon as possible to reschedule. See What is the most important information should know about DANYELZA. Swelling of the heart (myocarditis). Myocarditis has happened in adolescents ages 12 to 18 within days of receiving DANYELZA. Tell your healthcare provider if you get any signs or symptoms of myocarditis, including:. chest pain. shortness of breath irregular heartbeat or feel like your heart is racing. High blood pressure (hypertension). High blood pressure is common in people who receive DANYELZA. Your blood pressure will be monitored during your DANYELZA infusion, and at least each day on Days to of each DANYELZA treatment cycle. Tell your healthcare provider right away if you get any signs or symptoms of high blood pressure, including:. headaches. seizures. nausea or vomiting. chest pain. dizziness. visual changes. shortness of breath. feeling that your heart is pounding or racing (palpitations). nose bleeds. Decreased blood pressure (orthostatic hypotension) that can be severe and require hospitalization. You may feel dizzy, lightheaded, or pass out (faint) when you rise too quickly from sitting or lying position. Your healthcare provider will monitor your blood pressure before you start and during treatment with DANYELZA. fast heart rate. vomiting cough. nausea. decreased white blood cell, red blood cell, and platelet counts. diarrhea. decreased appetite. tiredness. skin rashes. decreased level of potassium, sodium, and phosphate in the blood. hives fever. headache. injection site reaction. swelling of the body or only in one part of the body. anxiety. irritability. increased liver function blood tests. decreased blood sugar level. decreased calcium levels in the blood decreased protein levels (albumin) in the blood.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Neurotoxicity: Peripheral neuropathy, neurological disorders of the eye, and prolonged urinary retention have also occurred. Permanently discontinue as recommended. (2.3, 5.2)Myocarditis: Withhold, reduce dose, or discontinue based on severity. (2.3, 5.3)Hypertension: Monitor blood pressure during and after infusion as recommended. Withhold, reduce infusion rate, or discontinue based on severity. (2.3, 5.4)Orthostatic Hypotension: Severe orthostatic hypotension, including cases requiring hospitalization, have occurred. Withhold, reduce dose, or discontinue based on severity. (2.3, 5.5)Embryo-Fetal Toxicity: May cause fetal harm. Advise females of reproductive potential of potential risk to fetus and to use effective contraception. (5.6). Neurotoxicity: Peripheral neuropathy, neurological disorders of the eye, and prolonged urinary retention have also occurred. Permanently discontinue as recommended. (2.3, 5.2). Myocarditis: Withhold, reduce dose, or discontinue based on severity. (2.3, 5.3). Hypertension: Monitor blood pressure during and after infusion as recommended. Withhold, reduce infusion rate, or discontinue based on severity. (2.3, 5.4). Orthostatic Hypotension: Severe orthostatic hypotension, including cases requiring hospitalization, have occurred. Withhold, reduce dose, or discontinue based on severity. (2.3, 5.5). Embryo-Fetal Toxicity: May cause fetal harm. Advise females of reproductive potential of potential risk to fetus and to use effective contraception. (5.6). 5.1 Serious Infusion-Related Reactions. DANYELZA can cause serious infusion reactions requiring urgent intervention including fluid resuscitation, administration of bronchodilators and corticosteroids, intensive care unit admission, infusion rate reduction or interruption of DANYELZA infusion. Infusion-related reactions included hypotension, bronchospasm, hypoxia, and stridor [see Adverse Reactions (6.1)]. Serious infusion-related reactions occurred in 4% of patients in Study 201 and in 18% of patients in Study 12-230. Infusion-related reactions of any Grade occurred in 100% of patients in Study 201 and 94% of patients in Study 12-230. Hypotension of any grade occurred in 100% of patients in Study 201 and 89% of patients in Study 12-230. In Study 201, 68% of patients experienced Grade or infusion reactions; and in Study 12-230, 32% of patients experienced Grade or infusion reactions. Anaphylaxis occurred in 12% of patients and patients (8%) permanently discontinued DANYELZA due to anaphylaxis in Study 201. One patient in Study 12-230 (1.4%) experienced Grade cardiac arrest 1.5 hours following completion of DANYELZA infusion.In Study 201, infusion reactions generally occurred within 24 hours of completing DANYELZA infusion, most often within 30 minutes of initiation. Infusion reactions were most frequent during the first infusion of DANYELZA in each cycle. Eighty percent of patients required reduction in infusion rate and 80% of patients had an infusion interrupted for at least one infusion-related reaction. Caution is advised in patients with pre-existing cardiac disease, as this may exacerbate the risk of severe hypotension.Premedicate with an antihistamine, acetaminophen, an H2 antagonist and corticosteroid as recommended [see Dosage and Administration (2.2)]. Monitor patients closely for signs and symptoms of infusion reactions during and for at least hours following completion of each DANYELZA infusion in setting where cardiopulmonary resuscitation medication and equipment are available. Reduce the rate, interrupt infusion, or permanently discontinue DANYELZA based on severity and institute appropriate medical management as needed [see Dosage and Administration (2.3) and Contraindications (4)]. 5.2 Neurotoxicity DANYELZA can cause severe neurotoxicity, including severe neuropathic pain, transverse myelitis, and reversible posterior leukoencephalopathy syndrome.. PainPain, including abdominal pain, bone pain, neck pain, and extremity pain, occurred in 100% of patients in Study 201 and 94% of patients in Study 12-230. Grade pain occurred in 72% of patients in Study 201. One patient in Study 201 (4%) required interruption of an infusion due to pain. Pain typically began during the infusion of DANYELZA and lasted median of less than one day in Study 201 (range less than one day and up to 62 days) [see Adverse Reactions (6.1)].Premedicate with drugs that treat neuropathic pain (e.g., gabapentin) and oral opioids. Administer intravenous opioids as needed for breakthrough pain [see Dosage and Administration (2.2)]. Permanently discontinue DANYELZA based on severity [see Dosage and Administration (2.3)]. Transverse MyelitisTransverse myelitis has occurred with DANYELZA. Permanently discontinue DANYELZA in patients who develop transverse myelitis [see Dosage and Administration (2.3)].. Reversible Posterior Leukoencephalopathy Syndrome (RPLS) Reversible posterior leukoencephalopathy syndrome (RPLS) (also known as posterior reversible encephalopathy syndrome or PRES) occurred in (2.8%) patients in Study 12-230. Events occurred and days following completion of the first cycle of DANYELZA. Monitor blood pressure during and following DANYELZA infusion and assess for neurologic symptoms [see Warnings and Precautions (5.3)]. Permanently discontinue DANYELZA in case of symptomatic RPLS [see Dosage and Administration (2.3) and Adverse Reactions (6.1)].. Peripheral NeuropathyPeripheral neuropathy, including peripheral sensory neuropathy, peripheral motor neuropathy, paresthesia, and neuralgia, occurred in 32% of patients in Study 201 and in 25% of patients in Study 12-230. Most signs and symptoms of neuropathy began on the day of the infusion and neuropathy lasted median of 5.5 days (range to 22 days) in Study 201 and days (range to 22 days) in Study 12-230 [see Adverse Reactions (6.1)].Permanently discontinue DANYELZA based on severity [see Dosage and Administration (2.3)].. Neurological Disorders of the Eye Neurological disorders of the eye including unequal pupils, blurred vision, accommodation disorder, mydriasis, visual impairment, and photophobia occurred in 24% of patients in Study 201 and 19% of patients in Study 12-230. Neurological disorders of the eye lasted median of 17 days (range to 84 days) in Study 201 with two patients (8%) experiencing an event that had not resolved at the time of data cutoff, and median of day (range less than one day to 21 days) in Study 12-230. Permanently discontinue DANYELZA based on severity [see Dosage and Administration (2.3) and Adverse Reactions (6.1)]. Prolonged Urinary Retention Urinary retention occurred in (4%) patient in Study 201 and in patients (4%) in Study 12-230. All events in both studies occurred on the day of an infusion of DANYELZA and lasted between and 24 days. Permanently discontinue DANYELZA in patients with urinary retention that does not resolve following discontinuation of opioids [see Dosage and Administration (2.3) and Adverse Reactions (6.1)]. 5.3 Myocarditis. Myocarditis has occurred in adolescent patients receiving DANYELZA in clinical trials and expanded access programs. Myocarditis occurred within days of receiving DANYELZA requiring drug interruption. Monitor for signs and symptoms of myocarditis during treatment with DANYELZA. Withhold, reduce the dose, or permanently discontinue DANYELZA based on severity [see Dosage and Administration (2.3)]. 5.4 Hypertension. Hypertension occurred in 44% of patients in Study 201 and 28% of patients in Study 12-230 who received DANYELZA. Grade or hypertension occurred in 4% of patients in Study 201 and 7% of patients in Study 12-230. Four patients (6%) in Study 12-230 permanently discontinued DANYELZA due to hypertension. In both studies, most events occurred on the day of DANYELZA infusion and occurred up to days following an infusion of DANYELZA. Do not initiate DANYELZA in patients with uncontrolled hypertension. Monitor blood pressure during infusion, and at least daily on Days to of each cycle of DANYELZA and evaluate for complications of hypertension including RPLS [see Warnings and Precautions (5.2)]. Interrupt DANYELZA infusion and resume at reduced rate, or permanently discontinue DANYELZA based on the severity [see Dosage and Administration (2.3) and Adverse Reactions (6.1)].. 5.5 Orthostatic Hypotension. Orthostatic hypotension has occurred in patients receiving DANYELZA in clinical trials and expanded access programs. Severe orthostatic hypotension, including cases requiring hospitalization, have occurred. Cases occurred within hours to days of DANYELZA infusions in any cycle.In patients with symptoms of orthostatic hypotension, monitor postural blood pressure prior to initiating treatment with DANYELZA and as clinically indicated with subsequent dosing. Withhold, reduce dose, or permanently discontinue DANYELZA based on severity [see Dosage and Administration (2.3) ].. 5.6 Embryo-Fetal Toxicity. Based on its mechanism of action, DANYELZA may cause fetal harm when administered to pregnant woman. Advise females of reproductive potential, including pregnant women, of the potential risk to fetus. Advise females of reproductive potential to use effective contraceptive during treatment with DANYELZA and for two months after the last dose. [see Use in Specific Populations (8.1, 8.3)].