Naxitamab for High-Risk Neuroblastoma
Recruiting in Palo Alto (17 mi)
+8 other locations
Age: < 65
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Giselle Sholler
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 1 jurisdiction
Trial Summary
What is the purpose of this trial?This trial is testing naxitamab with standard chemotherapy for high-risk neuroblastoma. Patients with a specific genetic change will also receive ceritinib. Naxitamab helps the immune system attack cancer, and ceritinib stops cancer cell growth. The goal is to improve survival rates for these patients.
Do I need to stop my current medications for the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on any investigational drugs or immunosuppressive treatments (except local steroids) within 4 weeks before joining the trial.
What data supports the effectiveness of the drug naxitamab for high-risk neuroblastoma?
Research shows that naxitamab, when combined with other treatments, can be effective for patients with high-risk neuroblastoma, especially when used early in treatment. In one study, patients receiving naxitamab-based therapy had improved long-term outcomes, with some achieving complete remission and better survival rates.
12345Is naxitamab safe for humans?
Naxitamab has been studied in patients with high-risk neuroblastoma, and common side effects include pain, high blood pressure, and manageable allergic reactions. Serious side effects were rare, and the treatment was generally well-tolerated, even in young children.
12345How is the drug naxitamab unique for treating high-risk neuroblastoma?
Naxitamab is unique because it is a humanized monoclonal antibody specifically targeting GD2, a molecule found on neuroblastoma cells, and it is approved for outpatient use in combination with granulocyte-macrophage colony-stimulating factor. This allows for treatment of relapsed or refractory high-risk neuroblastoma in the bone or bone marrow, offering a novel approach compared to traditional chemotherapy.
12345Eligibility Criteria
This trial is for children and young adults up to 21 years old with newly diagnosed high-risk neuroblastoma. Participants must have certain types of the disease, good liver and kidney function, and not be pregnant or breastfeeding. They should agree to use effective contraception if applicable. Those who've had previous systemic therapy beyond one cycle or are on immunosuppressants may not qualify.Participant Groups
The study tests adding naxitamab to standard chemotherapy during the first five cycles of treatment for neuroblastoma. For patients with an ALK mutation, ceritinib will also be included once test results are available. The goal is to see if this combination improves response rates and survival compared to standard therapy alone.
2Treatment groups
Experimental Treatment
Group I: Subjects with ALK aberrationExperimental Treatment2 Interventions
5 cycles of standard of care induction + naxitimab + ceritinib
Naxitimab on Days 1, 3, and 5 of each cycle Ceritinib once daily on every day of study
Group II: Subjects with ALK Wildtype or UnknownExperimental Treatment1 Intervention
5 cycles of standard of care induction + naxitimab
Naxitimab on Days 1, 3, and 5 of each cycle
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:
UCSF Benioff Children's Hospital Oakland-Oakland, CA
Levine Children's HospitalCharlotte, NC
Kapiolani Medical Center for Women and ChildrenHonolulu, HI
Augusta University HealthAugusta, GA
More Trial Locations
Loading ...
Who is running the clinical trial?
Giselle ShollerLead Sponsor
Wake Forest University Health SciencesLead Sponsor
Y-mAbsCollaborator
References
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.
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.
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.