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In 2 Trials, DANYELZA® Was Studied in an Outpatient Setting | DANYELZA
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In Study 201 and Study 12-230, DANYELZA® with GM-CSF was studied in an outpatient setting1

STUDY 201
STUDY 12-230
Study design1,2

A Phase II, open-label, single-arm, multicenter trial of 25 patients

bottom arrow22 patients were evaluated in the efficacy analysis of the ongoing study

A Phase I/II,* open-label, single-arm, single-center trial of 72 patients

bottom arrow38 patients were evaluated in the efficacy analysis

Endpoints1,2
Primary

bottom arrowOverall response rate (ORR)

  • Complete response (CR)
  • Partial response (PR)
Secondary

bottom arrowDuration of response (DOR)

bottom arrowSafety

Eligibility criteria2
Inclusion

bottom arrowPatients must have R/R high-risk neuroblastoma in bone and/or bone marrow and demonstrated a PR, MR, or SD on prior therapy

bottom arrowAll patients received at least 1 prior systemic therapy to treat disease outside of the bone and/or bone marrow

bottom arrowStudy 201: Preplanned radiation to the primary site was allowed; assessment of response excluded sites that received radiation

bottom arrowStudy 12-230: Radiation was permitted to bony and soft tissue lesions; assessment of response excluded sites that received radiation

Exclusion

bottom arrowPatients with progressive disease

*Phase I established the dose and assessed toxicity and Phase II assessed the anti-tumor activity and safety of DANYELZA with GM-CSF in patients with R/R high-risk neuroblastoma.1 The major efficacy outcome measure was confirmed ORR according to the revised International Neuroblastoma Response Criteria (INRC), as determined by independent pathology and imaging review, that was confirmed by at least 1 subsequent assessment. Responses were observed in the bone, bone marrow, or both bone and bone marrow. DOR was an additional outcome efficacy measure in Study 201 and a major efficacy outcome in Study 12-230.2
MR=minor response; R/R=refractory or relapsed; SD=stable disease.

DANYELZA clinical trials included patients with R/R high-risk neuroblastoma in the bone and/or bone marrow1-3

DANYELZA clinical trials patient type chart DANYELZA-trial-patients

PD=progressive disease.

Across DANYELZA studies, baseline characteristics were similar and included patients with poor prognostic factors1,4,5

Study design table DANYELZA Baseline Characteristics

ASCT=autologous stem cell transplant; INSS=International Neuroblastoma Staging System.

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INRG=International Neuroblastoma Risk Group.

References: 1. Park JR, Bagatell R, Cohn SL, et al. J Clin Oncol. 2017;35(22):2580-2587. 2. DuBois SG, Kalika Y, Lukens JN, et al. J Pediatr Hematol Oncol. 1999;21(3):181-189.
3. Smith V, Foster J. Children (Basel). 2018;5(9):114. 4. Irwin MS, Naranjo A, Zhang FF, et al. J Clin Oncol. 2021;39:3229-3241. 5. Sharp SE, Trout AT, Weiss BD, et al. Radiographics. 2016;36:258-278. 6. Garaventa A, Poetschger U, Valteau-Couanet D, et al. J Clin Oncol. 2021;39(23):2552-2563. 7. Pinto N, Naranjo A, Hibbitts E, et al. Eur J Cancer. 2019;112:66-79.
8. Yanik GA, Parisi MT, Naranjo A, et al. J Nucl Med. 2018;59:502-508. 9. Yanik GA, Parisi MT, Shulkin BL, et al. J Nucl Med. 2013;54(4):541-548. 10. Streby KA, Parisi MT, Shulkin BL, et al. Pediatr Blood Cancer. 2024;70(8):e30418.

References: 1. Data on file. Y-mAbs Therapeutics, Inc. 2. DANYELZA® [package insert]. New York, NY: Y-mAbs Therapeutics, Inc.; 2024.

References: 1. DANYELZA® [package insert]. New York, NY: Y-mAbs Therapeutics, Inc.; 2024.

References:  1. DANYELZA® [package insert]. New York, NY: Y-mAbs Therapeutics, Inc.; 2024. 2. Data on file. Y-mAbs Therapeutics, Inc.

References:  1. DANYELZA® [package insert]. New York, NY: Y-mAbs Therapeutics, Inc.; 2024. 2. Cheung N-KV, Guo H, Hu J, et al. Oncoimmunology. 2012;1(4):477-486. 3. Lisby S, Liebenberg N, Bukrinski J, et al. Presented at the SIOP virtual congress. Abstract #945. October 16, 2024.

References: 1. DANYELZA® [package insert]. New York, NY: Y-mAbs Therapeutics, Inc.; 2024. 2. Data on file. Y-mAbs Therapeutics, Inc.

References: 1. DANYELZA® [package insert]. New York, NY: Y-mAbs Therapeutics, Inc.; 2024. 2. Data on file. Y-mAbs Therapeutics, Inc. 3. NIH US National Library of Medicine.
https://clinicaltrials.gov/ct2/show/NCT01419834?term=NCT01419834&draw=2&rank=1. Accessed June 15, 2024.

*In refractory or relapsed high-risk neuroblastoma.

References: 1. DANYELZA® [package insert]. New York, NY: Y-mAbs Therapeutics, Inc.; 2024. 2. Cheung N-KV, Guo H, Hu J, et al. Oncoimmunology. 2012;1(4):477-486. 3. Lisby S, Liebenberg N, Bukrinski J, et al. Presented at the SIOP virtual congress. Abstract #945. October 16, 2024.

INDICATION

DANYELZA is indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), for the treatment of pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partiaI response, minor response, or stable disease to prior therapy.

This indication is approved under accelerated approval based on overalI response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

CONTRAINDICATION

DANYELZA is contraindicated in patients with a history of severe hypersensitivity reaction to naxitamab-gqgk. Reactions have included anaphylaxis.

WARNINGS AND PRECAUTIONS
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.

IMPORTANT SAFETY INFORMATION

WARNING: SERIOUS INFUSION-RELATED REACTIONS and NEUROTOXICITY

Serious Infusion-Related Reactions

  • DANYELZA can cause serious infusion reactions, including cardiac arrest, anaphylaxis, hypotension, bronchospasm, and stridor. lnfusion reactions of any Grade occurred in 94-100% of patients. Severe infusion reactions occurred in 32-68% and serious infusion reactions occurred in 4-18% of patients in DANYELZA clinical studies.
  • Premedicate prior to each DANYELZA infusion as recommended and monitor patients for at least 2 hours following completion of each infusion. Reduce the rate, interrupt infusion, or permanently discontinue DANYELZA based on severity.
  • Neurotoxicity

  • 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.
  • Premedicate to treat neuropathic pain as recommended. Permanently discontinue DANYELZA based on the adverse reaction and severity.
CONTRAINDICATION

DANYELZA is contraindicated in patients with a history of severe hypersensitivity reaction to naxitamab-gqgk. Reactions have included anaphylaxis.

WARNINGS AND PRECAUTIONS
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.

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 3 or 4 infusion reactions; and in Study 12-230, 32% of patients experienced Grade 3 or 4 infusion reactions. Anaphylaxis occurred in 12% of patients and two patients (8%) permanently discontinued DANYELZA due to anaphylaxis in Study 201. One patient in Study 12-230 (1.4%) experienced a Grade 4 cardiac arrest 1.5 hours following completion of DANYELZA infusion.

In Study 201, infusion reactions generally occurred within 24 hours of completing a 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. Monitor patients closely for signs and symptoms of infusion reactions during and for at least 2 hours following completion of each DANYELZA infusion in a 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.

Neurotoxicity

DANYELZA can cause severe neurotoxicity, including severe neuropathic pain, transverse myelitis, and reversible posterior leukoencephalopathy syndrome.

Pain
Pain, 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 3 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 a median of less than one day in Study 201 (range less than one day and up to 62 days).

Premedicate with drugs that treat neuropathic pain (e.g., gabapentin) and oral opioids. Administer intravenous opioids as needed for breakthrough pain. Permanently discontinue DANYELZA based on severity.

Transverse Myelitis
Transverse myelitis has occurred with DANYELZA. Permanently discontinue DANYELZA in patients who develop transverse myelitis.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS)
Reversible posterior leukoencephalopathy syndrome (RPLS) (also known as posterior reversible encephalopathy syndrome or PRES) occurred in 2 (2.8%) patients in Study 12-230. Events occurred 2 and 7 days following completion of the first cycle of DANYELZA. Monitor blood pressure during and following DANYELZA infusion and assess for neurologic symptoms. Permanently discontinue DANYELZA in case of symptomatic RPLS.

Peripheral Neuropathy
Peripheral 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 a median of 5.5 days (range 0 to 22 days) in Study 201 and 0 days (range 0 to 22 days) in Study 12-230.

Permanently discontinue DANYELZA based on severity.

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 a median of 17 days (range 0 to 84 days) in Study 201 with two patients (8%) experiencing an event that had not resolved at the time of data cutoff, and a median of 1 day (range less than one day to 21 days) in Study 12-230. Permanently discontinue DANYELZA based on severity.

Prolonged Urinary Retention
Urinary retention occurred in 1 (4%) patient in Study 201 and in 3 patients (4%) in Study 12-230. All events in both studies occurred on the day of an infusion of DANYELZA and lasted between 0 and 24 days. Permanently discontinue DANYELZA in patients with urinary retention that does not resolve following discontinuation of opioids.

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.

Hypertension

Hypertension occurred in 44% of patients in Study 201 and 28% of patients in Study 12-230 who received DANYELZA. Grade 3 or 4 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 9 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 1 to 8 of each cycle of DANYELZA and evaluate for complications of hypertension including RPLS. Interrupt DANYELZA infusion and resume at a reduced rate, or permanently discontinue DANYELZA based on the severity.

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 6 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.

Embryo-Fetal Toxicity

Based on its mechanism of action, DANYELZA may cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential, including pregnant women, of the potential risk to a fetus. Advise females of reproductive potential to use effective contraceptive during treatment with DANYELZA and for two months after the last dose.

ADVERSE REACTIONS

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 3 or 4 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.

Please see full Prescribing Information and Patient Information for DANYELZA including Boxed Warning on serious infusion-related reactions and neurotoxicity.

Reference: 1. DANYELZA® [package insert]. New York, NY: Y-mAbs Therapeutics, Inc.; 2024.

References: 1. Data on file. Y-mAbs Therapeutics, Inc. 2. DANYELZA® [package insert]. New York, NY: Y-mAbs Therapeutics, Inc.; 2024. Available online at https://labeling.ymabs.com/danyelza. 3. Smith V, Foster J. High-risk neuroblastoma treatment review. Children (Basel). 2018;5(9):114. 4. Ahmed A, Zhang L, Reddivalla N, Hetherington M. Neuroblastoma in children: update on clinicopathologic and genetic prognostic factors. Pediatr Hematol Oncol. 2017;34(3):165-185. 5. London W, Castel V, Monclair T, et al. Clinical and biologic features predictive of survival after relapse of neuroblastoma: a report from International Neuroblastoma Risk Group project. J Clin Oncol. 2011;29(24):3286-3292.

References: 1. DANYELZA® [package insert]. New York, NY: Y-mAbs Therapeutics, Inc.; 2024. Available online at https://labeling.ymabs.com/danyelza. 2. National Cancer Institute. Published November 27, 2017. Accessed May 17, 2021. Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf

INDICATION View all

DANYELZA is indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), for the treatment of pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partiaI response, minor response, or stable disease to prior therapy.

This indication is approved under accelerated approval based on overalI response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

CONTRAINDICATION

DANYELZA is contraindicated in patients with a history of severe hypersensitivity reaction to naxitamablqgk. Reactions have included anaphylaxis.

WARNINGS AND PRECAUTIONS

Serious Infusion-Related Reactions

DANYELZA can cause serious infusion reactions requiting 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.

IMPORTANT SAFETY INFORMATION View all
IMPORTANT SAFETY INFO View all

WARNING: SERIOUS INFUSION-RELATED REACTIONS and NEUROTOXICITY

Serious Infusion-Related Reactions

  • DANYELZA can cause serious infusion reactions, including cardiac arrest, anaphylaxis, hypotension, bronchospasm, and stridor. lnfusion reactions of any Grade occurred in 94-100% of patients. Severe infusion reactions occurred in 32-68% and serious infusion reactions occurred in 4-18% of patients in DANYELZA clinical studies.
  • Premedicate prior to each DANYELZA infusion as recommended and monitor patients for at least 2 hours following completion of each infusion. Reduce the rate, interrupt infusion, or permanently discontinue DANYELZA based on severity.
  • Neurotoxicity

    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.
  • Premedicate to treat neuropathic pain as recommended. Permanently discontinue DANYELZA based on the adverse reaction and severity.