Naxitamab Plus GM-CSF Approved For R/R High-Risk Neuroblastoma in Bone or Bone Marrow
The FDA has approved naxitamab (Danyelza®, Y-mAbs Therapeutics, Inc.) plus granulocyte-macrophage colony-stimulating factor (GM-CSF) for pediatric patients aged one year and older and for adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have experienced a partial or minor response to prior therapy, or who have stable disease.
The approval was based on two open-label clinical trials, Study 201 and Study 12-230. "Neuroblastoma is a rare cancer but represents the most common extracranial solid tumor of childhood," write the authors of Study 201, led by Jaume Mora, MD, Scientific Director of the Oncology and Hematology Area at Sant Joan de Déu Barcelona Children's Hospital in Spain. "Most high-risk neuroblastoma patients present with or develop metastatic disease typically in bone or bone marrow. Despite advances in frontline multimodal therapy ~50% of patients relapse. Refractory or relapsed disease represents an unmet medical need."
Study 201 enrolled 22 patients with relapsed/refractory high-risk neuroblastoma in the bone or bone marrow whose disease progressed after initial treatment or who did not experience a sufficient response to therapy for progressive disease. Study 12-230 enrolled 38 patients with relapsed/refractory high-risk neuroblastoma in the bone or bone marrow whose disease was resistant to standard therapy. Patients in both trials were treated with 3 mg/kg naxitamab on Days 1, 3, and 5 of 4-week cycles, in combination with 250 µg/m2/day GM-CSF on Days -4 to 0 and 500 µg/m2/day on Days 1 through 5.
In Study 201, naxitamab plus GM-CSF produced an overall response rate of 45%, with 30% of responders achieving a response that lasted at least 6 months. In Study 12-230, naxitamab plus GM-CSF produced an overall response rate of 34%, with 23% of responders having a response that lasted at least 6 months. In both trials, responses were observed in either the bone, the bone marrow, or both.
The most common adverse events occurring in at least 25% of patients in either trial included 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 occurring in at least 5% of patients in either trial included 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.
The prescribing information for naxitamab includes a warning that this treatment can cause serious infusion-related reactions or neurotoxicity, such as severe neuropathic pain, transverse myelitis, or reversible posterior leukoencephalopathy (RPLS). Premedication should be administered prior to each naxitamab infusion, and patients should be monitored during treatment and for at least two hours after completion.
"Naxitamab offers a unique option for treatment of patients in the outpatient setting," conclude Dr. Mora and colleagues in their publication in the Journal of Clinical Oncology.
The recommended dosage of naxitamab is 3 mg/kg for a maximum of 150 mg/day, administered intravenously on Days 1, 3, and 5 of each treatment cycle, in combination with 250 µg/m2/day GM-CSF on Days -4 to 0 and 500 µg/m2/day on Days 1 through 5, with treatment cycles repeated every 4-8 weeks until complete or partial response.
For More Information
Mora J, Chan GC, Morgenstern DA et al (2020). Naxitamab, a new generation anti-GD2 monoclonal antibody (mAb) for treatment of relapsed/refractory high-risk neuroblastoma (HR-NB). J Clin Oncol. (ASCO Annual Meeting Abstracts) 38, (15_suppl). Abstract 10543. DOI:10.1200/JCO.2020.38.15_suppl.1054
US Food & Drug Administration (2020). FDA grants accelerated approval to naxitamab for high-risk neuroblastoma in bone or bone marrow[news release]. Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-naxitamab-high-risk-neuroblastoma-bone-or-bone-marrow?utm_medium=email&utm_source=govdelivery
Clinicaltrials.gov (2020). Naxitamab for high-risk neuroblastoma patients with primary refractory disease or incomplete response to salvage treatment in bone and/or bone marrow. NLM identifier: NCT03363373.
Clinicaltrials.gov (2020). Combination therapy of antibody hu3f8 with granulocyte- macrophage colony stimulating factor (gm-csf) in patients with relapsed/refractory high-risk neuroblastoma. NLM identifier: NCT01757626.
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