Naxitamab for High-Risk Neuroblastoma
Recruiting in Palo Alto (17 mi)
+19 other locations
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Y-mAbs Therapeutics
Must not be taking: Chemotherapy, Immunotherapy
Disqualifiers: Major organ dysfunction, Life-threatening infection, others
No Placebo Group
Prior Safety Data
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?Children and adults diagnosed with high-risk neuroblastoma patients with primary refractory disease or incomplete response to salvage treatment in bone and/or bone marrow will be treated for up to 101 weeks with naxitamab and granulocyte-macrophage colony stimulating factor (GM-CSF). Patients will be followed for up to five years after first dose.
Naxitamab, also known as hu3F8 is a humanised monoclonal antibody targeting GD2
Will I have to stop taking my current medications?
The trial requires that you stop any systemic anti-cancer therapy, including chemotherapy or immunotherapy, at least 3 weeks before starting the trial treatment.
What data supports the effectiveness of the drug Naxitamab for high-risk neuroblastoma?
Naxitamab, when used with other treatments like chemotherapy and granulocyte-macrophage colony-stimulating factor, has shown promising results in treating high-risk neuroblastoma, especially when given early. In one study, 47% of patients treated early achieved complete remission, and the overall survival rate was significantly improved.
12345Is naxitamab safe for humans?
Naxitamab has been studied in various clinical trials and is generally considered safe for humans, though it can cause side effects like pain, high blood pressure, and allergic reactions. Most side effects are manageable, and serious long-term issues are rare.
12345How is the drug naxitamab unique for treating high-risk neuroblastoma?
Naxitamab is unique because it is a humanized monoclonal antibody that specifically targets GD2, a molecule found on neuroblastoma cells, and is used in combination with granulocyte-macrophage colony-stimulating factor to enhance the immune response. It is approved for outpatient administration, which can be more convenient for patients, and is effective even in cases where the disease has relapsed or is resistant to other treatments.
12345Eligibility Criteria
This trial is for children and adults with high-risk neuroblastoma that hasn't fully responded to previous treatments or is considered refractory. Participants should have a life expectancy of at least 6 months and their disease must be present in the bone or bone marrow, but not outside these areas. They shouldn't have had cancer therapy within the last 3 weeks and must not have severe organ dysfunction or active serious infections.Inclusion Criteria
My neuroblastoma is high-risk and hasn't fully responded to treatment.
Life expectancy ≥ 6 months
I have been diagnosed with neuroblastoma.
Exclusion Criteria
My neuroblastoma is detectable outside of my bones and bone marrow.
I do not have a severe infection that is putting my life at risk.
My major organs are functioning well, except possibly my hearing, blood, kidneys, or liver.
+1 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive Naxitamab and GM-CSF treatment in cycles, repeated every 4 weeks initially, then every 8 weeks, for up to 101 weeks
101 weeks
Multiple visits per cycle, including days -4 to 5 for GM-CSF and days 1, 3, 5 for Naxitamab
End of Treatment
End of treatment visit occurs approximately 8 weeks after the last treatment cycle
8 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment for up to 5 years
5 years
Participant Groups
The study tests naxitamab combined with GM-CSF in patients with high-risk neuroblastoma over a period of up to 101 weeks. Naxitamab is an antibody targeting GD2 on cancer cells, while GM-CSF helps boost the immune system's response against the tumor.
1Treatment groups
Experimental Treatment
Group I: GM-CSF + NaxitamabExperimental Treatment1 Intervention
Each investigational cycle is started with 5 days of GM-CSF administered at 250 µg/m2/day in advance of the start of Naxitamab administration. GM-CSF is thereafter administered at 500 µg/m2/day on days 1 to 5. As standard treatment, Naxitamab is administered at 3 mg/kg/day on days 1, 3, and 5 totalling 9 mg/kg per cycle. Treatment cycles are repeated every 4 weeks until CR or PR followed by 5 additional cycles every 4 weeks (±1 week). Subsequent cycles are repeated every 8 weeks (±2 weeks) through 101 weeks from first infusion at the discretion of the investigator. After end of treatment patients will enter a long-term follow up for up to 3 years after end of treatment visit.
Naxitamab is already approved in United States for the following indications:
🇺🇸 Approved in United States as Danyelza for:
- High-risk neuroblastoma in bone or bone marrow demonstrating a partial response, minor response, or stable disease to prior therapy
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Riley Hospital for ChildrenIndianapolis, IN
Memorial Sloan Kettering Cancer CenterNew York, NY
The Hospital for Sick ChildrenToronto, Canada
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Who Is Running the Clinical Trial?
Y-mAbs TherapeuticsLead Sponsor
References
Outpatient administration of naxitamab in combination with granulocyte-macrophage colony-stimulating factor in patients with refractory and/or relapsed high-risk neuroblastoma: Management of adverse events. [2023]Naxitamab is a humanized GD2-binding monoclonal antibody that received accelerated approval from the U.S. Food and Drug Administration for refractory or relapsed high-risk neuroblastoma limited to bone or bone marrow. Trial 201 (NCT03363373) is an ongoing global clinical trial to evaluate the efficacy and safety of naxitamab in combination with granulocyte-macrophage colony-stimulating factor in this population.
Naxitamab combined with granulocyte-macrophage colony-stimulating factor as consolidation for high-risk neuroblastoma patients in complete remission. [2022]Naxitamab is a humanized anti-disialoganglioside (GD2) monoclonal antibody approved for treatment of bone/bone marrow refractory high-risk neuroblastoma (HR-NB). Compassionate use (CU) expanded access program at Hospital Sant Joan de Deu permitted treatment of patients in complete remission (CR). We here report the survival, toxicity, and relapse pattern of patients in first or second CR treated with naxitamab and sargramostim (GM-CSF).
Immunotherapy with anti-GD2 monoclonal antibody in infants with high-risk neuroblastoma. [2022]Anti-GD2 monoclonal antibodies (mAb) improve the prognosis of high-risk neuroblastoma (HR-NB). Worldwide experience almost exclusively involves toddlers and older patients treated after multimodality or second-line therapies, that is, many months postdiagnosis. In contrast, at our center, infants received anti-GD2 mAbs because this immunotherapy started during or immediately after induction chemotherapy. We now report on the feasibility, safety, and long-term survival in this vulnerable age group. Thirty-three HR-NB patients were <19 months old when started on 3F8 (murine mAb; n = 21) or naxitamab (humanized-3F8; n = 12), with 30″ to 90″ intravenous infusions. Patients received analgesics and antihistamines. Common toxicities (pain, urticaria, cough) were manageable, allowing outpatient treatment. Capillary leak, posterior reversible encephalopathy syndrome, and mAb-related long-term toxicities did not occur. Two 3F8 cycles were aborted due to bradycardia (a preexisting condition) and asthmatic symptoms, respectively. One patient received ½ dose of Day 1 naxitamab because of hypotension; full doses were subsequently administered. Post-mAb treatments included chemotherapy, radiotherapy, and anti-NB vaccine. Among 3F8 patients, 17/21 are in complete remission off all treatment at 5.6+ to 24.1+ (median 13.4+) years from diagnosis. Among naxitamab patients, 10/12 remain relapse-free post-mAb at 1.7+ to 4.3+ (median 3.1+) years from diagnosis. Toxicity was similar with short outpatient infusions and matched that observed with these and other anti-GD2 mAbs in older patients. These findings were reassuring given that naxitamab is dosed >2.5× higher (~270 mg/m2 /cycle) than 3F8, dinutuximab, and dinutuximab beta (70-100 mg/m2 /cycle). HR-NB in infants proved to be highly curable.
Naxitamab: First Approval. [2021]Naxitamab (DANYELZA®, naxitamab-gqgk) is a humanised (IgG1) anti-GD2 (hu3F8) monoclonal antibody was developed by the Memorial Sloan Kettering Cancer Center (with commercial rights licenced to Y-mAbs therapeutics Inc.) for the treatment of neuroblastoma, osteosarcoma and other GD2-positive cancers. Naxitamab was recently granted accelerated approval by the US FDA for marketing as treatment (in combination with granulocyte-macrophage colony-stimulating factor) for paediatric patients at least one year of age and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow demonstrating a partial response, minor response, or stable disease to prior therapy. This article summarizes the milestones in the development of naxitamab leading to this first approval.
Early Salvage Chemo-Immunotherapy with Irinotecan, Temozolomide and Naxitamab Plus GM-CSF (HITS) for Patients with Primary Refractory High-Risk Neuroblastoma Provide the Best Chance for Long-Term Outcomes. [2023]Patients with high-risk neuroblastoma (HR-NB) who are unable to achieve a complete response (CR) to induction therapy have worse outcomes. We investigated the combination of humanized anti-GD2 mAb naxitamab (Hu3F8), irinotecan (I), temozolomide (T), and sargramostim (GM-CSF)-HITS-against primary resistant HR-NB. Eligibility criteria included having a measurable chemo-resistant disease at the end of induction (EOI) treatment. Patients were excluded if they had progressive disease (PD) during induction. Prior anti-GD2 mAb and/or I/T therapy was permitted. Each cycle, administered four weeks apart, comprised Irinotecan 50 mg/m2/day intravenously (IV) plus Temozolomide 150 mg/m2/day orally (days 1-5); naxitamab 2.25 mg/kg/day IV on days 2, 4, 8 and 10, (total 9 mg/kg or 270 mg/m2 per cycle), and GM-CSF 250 mg/m2/day subcutaneously was used (days 6-10). Toxicity was measured using CTCAE v4.0 and responses through the modified International Neuroblastoma Response Criteria (INRC). Thirty-four patients (median age at treatment initiation, 4.9 years) received 164 (median 4; 1-12) HITS cycles. Toxicities included myelosuppression and diarrhea, which was expected with I/T, and pain and hypertension, expected with naxitamab. Grade ≥3-related toxicities occurred in 29 (85%) of the 34 patients; treatment was outpatient. The best responses were CR = 29% (n = 10); PR = 3% (n = 1); SD = 53% (n = 18); PD = 5% (n = 5). For cohort 1 (early treatment), the best responses were CR = 47% (n = 8) and SD = 53% (n = 9). In cohort 2 (late treatment), the best responses were CR = 12% (n = 2); PR = 6% (n = 1); SD = 53% (n = 9); and PD = 29% (n = 5). Cohort 1 had a 3-year OS of 84.8% and EFS 54.4%, which are statistically significant improvements (EFS p = 0.0041 and OS p = 0.0037) compared to cohort 2. In conclusion, naxitamab-based chemo-immunotherapy is effective against primary chemo-resistant HR-NB, increasing long-term outcomes when administered early during the course of treatment.