Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label 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 partial response, minor response, or stable disease to prior therapy. FDA label
Also known as Hu3F8, humanized anti-GD2 antibody, Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF), Danyelza
Naxitamab · 9 trials · 9 indications
Measured by the presence of radiologically assessable disease by cross-sectional computed tomography (CT) or Magnetic resonance imaging (MRI) imaging and/or by metaiodobenzylguanidine (MIBG) or positron emission tomography (PET) scans and bone marrow (BM) response for subjects with newly-diagnosed high-risk neuroblastoma according to the 1993 International Neuroblastoma Response Criteria (INRC) and compare to relevant historical controls.
EFS is defined as the time from surgery to relapse or death from any cause, recurrence of tumor or second malignancy.
Patients are considered a response failure under this protocol if progressive disease is evident before two years. Deaths from toxicity attributable to protocol treatment will be counted as events. Patients who withdraw or are lost to followup before two years will be considered as progressions.
This measure will be assessed by evaluating treatment side effects.
This measure will be assessed using the 1993 International Neuroblastoma Response Criteria (INRC) criteria.
as defined by International NB Response Criteria. Disease status is defined by the International NB Response Criteria. Complete response/remission (CR): no evidence of disease. Very good partial response/remission (VGPR): \>90% decrease in all disease parameters, except bone scan unchanged or improved; bone marrow must be free of disease. Partial response/remission: \>50% decrease in all disease parameters, except bone scan unchanged or improved; no more than 1 positive bone marrow site. Mixed response: \>50% decrease in \>1 but not all disease markers. Stable disease: \<50% decrease in all tumor markers. Progressive disease: new lesion, or \>25 % increase in any disease marker.
hu3F8 when combined with GM-CSF. DLT is defined after 1 cycle. Seventeen dosage levels of hu3F8 will be tested with three to six patients at each dosage level.
of the humanized anti GD2 antibody hu3F8 when combined with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in patients with high risk neuroblastoma. All observed adverse events, regardless of treatment group or suspected causal relationship to study drug will be recorded. Adverse events will be identified and graded using the Common Toxicity Criteria Version 4.0
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
The duration of naxitamab infusion that is safe and tolerable will be measured using the endpoint of an occurrence of any dose limiting toxicity. A modified 3+3 design will be used, where the 'modification' permits a single duration level de-escalation in addition to the typical duration group level escalation.
The regimen will be considered safe if there are no toxicities requiring discontinuation of therapy in at least 9/10 patients during the first two cycles.
Response assessment will be based on the best response over the course of four cycles. Disease response for NB will use the International NB Response Criteria. Patients who withdraw from the study prior to cycle 4 with \< partial response will also not be considered evaluable for response and will be replaced.
| Arm | Type | Description |
|---|---|---|
| HRNB Newly diagnosed subjects | EXPERIMENTAL | 5 cycles of standard of care induction + naxitimab Naxitimab on Days 1, 3, and 5 of each cycle |
| humanized anti-GD2 antibody, hu3F8, when combined with GM-CSF | EXPERIMENTAL | One cycle consists of treatment with hu3F8 at a dose of 2.4mg/kg/dose for 3 days (day 1, 3, and 5) in the presence of subcutaneous (sc) GM-CSF (day -4 through 5). These 3 doses of hu3F8 and 10 days of GM-CSF constitute a treatment cycle. Cycles are repeated at \~2-4 week intervals between first days of hu3F8, through 5 cycles. A maximum of 5 cycles will be administered on protocol. If elevations of amylase and/or lipase (\>Grade 1) or clinical signs suggestive of pancreatitis (e.g. upper abdominal pain) occurs, naxitamab and GM-CSF doses should be held until improvement of toxicity to ≤Grade 1 if laboratory elevations and/or pancreatitis is possibly related to either naxitamab or GM-CSF. |
| Hu3F8/GM-CSF Plus Isotretinoin | EXPERIMENTAL | In this phase II single arm trial, patients with HR-NB in first CR or VGPR undergo consolidation by using hu3F8/GM-CSF x5 cycles and isotretinoin x6 cycles. Isotretinoin starts after cycle 2 of hu3F8/GM-CSF. |
| Naxitamab and GM-CSF | EXPERIMENTAL | All enrolled patients receive Naxitamab and GM-CSF in combination with induction therapy for newly-diagnosed high-risk neuroblastoma |
| Humanized Anti-GD2 Antibody Hu3F8 | EXPERIMENTAL | This is a phase I study to assess the safety and feasibility of combining HLA-mismatched (KIR ligand incompatible) NK cells with hu3F8 in high-risk NB patients. Following chemotherapy, patients will be treated in sequential groups with a minimum of 3 patients/ dose of NK cells. Three dose levels of NK cells, starting at dose level 1, will be evaluated in this treatment protocol. The goal dose for each dose level is the high boundary (e.g. 9.9x10\^6/kg in level 1; 14.9x10\^6/kg in level 2, etc), but a range is provided to allow for cases where the goal dose cannot be achieved. |
| Hu3F8 with GM-CSF | EXPERIMENTAL | The phase I single arm trial assesses escalating doses of iv hu3F8 (days 1, 3, 5) in the presence of sc GM-CSF (day -4 through 5). These 3 doses of hu3F8 and 10 days of GM-CSF constitute a treatment cycle. The expansion phase II single arm trial assesses the anti-NB activity of hu3F8+GM-CSF.in 3 groups of patients: Group 1 patients have primary refractory disease (no prior relapse but incomplete response to treatment) in BM as documented by histology and/or 123I-MIBG scan. Group 2 patients are in ≥2nd CR and at high risk for another relapse. Group 3 patients have secondary refractory disease (prior relapse and incomplete response to retrieval therapy) in BM as documented by histology and/or 123I-MIBG scan. Ph II: Groups 1 \& 3 pts can continue to get cycles every 1-2 months for up to 24 months from study enrollment or until they receive 5 cycles after a major response (CR or PR) is achieved. |
| expansion phase II single arm trial | EXPERIMENTAL | Group 1 patients have primary refractory disease (no prior relapse but incomplete response to treatment) in BM as documented by histology and/or 123\^I-MIBG scan. Group 2 patients are in \>2nd CR/VGPR and at high risk for another relapse. Group 3 patients have secondary refractory disease (prior relapse and incomplete response to retrieval therapy) in BM as documented by histology and/or 123\^I-MIBG scan. GM-CSF can be omitted if patients have a history of an allergy to GM-CSF or develop an allergic reaction to GM-CSF after initiating therapy while on the protocol. |
| Treatment with Naxitamab and Sacituzumab Govitecan IV Q3W | EXPERIMENTAL | Patients receive naxitamab IV on days 2, 4, and 6 of cycles 1-8 and sacituzumab govitecan IV days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
| Naxitamab Infusion+ Ironotecan + Temozolomide + Sargramostim | EXPERIMENTAL | Participants will be enrolled in a modified 3+3 design to establish a maximum tolerated, infusion duration for Naxitamab. Dosage will start at Duration Level 1 and will de-escalate to Duration Level -1 or escalate to Duration Level 2 according to dose-limiting toxicity (DLT) criteria. * Baseline visit * Cycle 1 (21 day cycle): * Days 1, 3, and 5: Predetermined dose of Naxitamab 1x daily * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 through 5: Predetermined dose of Ironotecan 1x daily * Days 6 through 12: predetermined dose of Sargramostim 1x daily * Cycles 2 through 6 (21 day cycles): * Imaging on Cycles 2, 4, and 6 * Days 1, 3, and 5: Predetermined dose of Naxitamab 1x daily * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 through 5: Predetermined dose of Ironotecan 1x daily * Days 6 through 12: predetermined dose of Sargramostim 1x daily * End of treatment visit * Follow up at 1 year post-treatment |
| Hu3F8, Irinotecan/Temozolomide and Sargramostim (HITS) | EXPERIMENTAL | Each cycle consists of four doses of hu3F8, five doses each of irinotecan and temozolomide and five doses of GM-CSF. |
| Name | Type | Description |
|---|---|---|
| Naxitamab | DRUG | Naxitamab is a humanized (IgG1) anti-GD2 (hu3F8) monoclonal antibody for the treatment of neuroblastoma, osteosarcoma and other GD2-positive cancers. Naxitamab was granted accelerated approval by the FDA in 2020 as treatment (in combination with granulocyte-macrophage colony-stimulating factor - GM-CSF) for pediatric 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 |
| humanized anti-GD2 antibody | BIOLOGICAL | - |
| GM-CSF | DRUG | - |
| Hu3F8 | BIOLOGICAL | Day 1: hu3F8 infused iv over \~30 to 90 minutes. Day 3: hu3F8 infused iv over \~30 to 90 minutes. Day 5: hu3F8 infused iv over \~30 to 90 minutes. |
| Isotretinoin | DRUG | Isotretinoin is administered at 160 mg/m2/d, divided into two doses, x14 days. |
| cyclophosphamide | DRUG | chemotherapy with intravenous (IV) cyclophosphamide 50mg/kg/day (for patients with body weight\<70kg) or 1500mg/m\^2/day (for patients with body weight ≥70kg) for two days (days -6 and -5). |
| NK cells | BIOLOGICAL | Day 0: NK cell infusion. NK cells are resuspended in Normasol at a concentration no less than 5 x 10\^6cells/mL. The patient is pre-medicated as per standard cell product infusion. The cell product is infused through a central venous catheter. Patients will be evaluated clinically by vital signs pre- and approximately 30 minutes post infusion of NK cells and thereafter at approximately 1 hour intervals for 4 hours. |
| rIL-2 | DRUG | On day 0, daily from +2 through +4, day +6, and day +8, rIL-2 is administered subcutaneously at 6 x 10\^5 U/m\^2/day. |
| Hu3F8 With GM-CSF | BIOLOGICAL | Ph I: 1 cycle consists of treatment with hu3F8 for 3 days (day 1, 3 \& 5). GM-CSF starts 5 days in advance of each hu3F8 cycle at 250 mcg/m\^2/day (day -4 to day 0), \& at 500 mcg/m\^2/day x 5 days (day 1 to day 5). Hu3F8 cycles are 5 days. Ph II pts may receive treatment on a modified schedule of 3 doses of IV hu3F8 over a maximum of 10 days, as needed. With modified schedules of hu3F8, GM-CSF will be administered at 250 mcg/m2/day x5 days before the 1st dose of hu3F8, as with the standard schedule, but then GM-CSF at 500 mcg/m2/day will be administered on day of the 1st dose of hu3F8, on the day before and on the day of the 2nd dose of hu3F8, and on the day before and on the day of the 3rd dose of hu3F8. Cycles are repeated at 2-4 week intervals between 1st days of hu3F8, through 4 cycles. Pts who complete 4 cycles of treatment w/o complications or disease progression have the option of continuing treatment for up to 24 months from their 1st dose of hu3F8. |
| Sacituzumab govitecan | DRUG | Given by IV |
| Irinotecan | DRUG | Topoisomerase Inhibitor, single-dose vial, via intravenous infusion per standard of care |
| Temozolomide | DRUG | Alkylating agent, capsule, via orally (by mouth) per standard of care |
| Sargramostim granulocyte-macrophage colony stimulating factor | DRUG | Recombinant human granulocyte-macrophage colony stimulating factor (rhu GM-CSF), multi-use vial, via subcutaneously (under the skin) injection per standard of care |
Inclusion Criteria: 1. Diagnosis: Subjects must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular or intermixed) verified by histology or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites. Subjects with the following disease stage...
Naxitamab is an investigational monoclonal antibody being studied for high-risk neuroblastoma, relapsed or refractory neuroblastoma, metastatic triple-negative breast cancer, and recurrent osteosarcoma. It is being developed by Y-mAbs Therapeutics, Inc. (ticker: YMAB) and is currently in Phase 2 clinical development.
Naxitamab targets GD2, a disialoganglioside expressed on neuroblastoma cells and other tumors. As a humanized anti-GD2 monoclonal antibody, it binds GD2 and is designed to trigger immune-mediated destruction of GD2-positive tumor cells. The drug is also known as Hu3F8 or hu3F8.
Naxitamab is being developed by Y-mAbs Therapeutics, Inc., which trades under the ticker symbol YMAB. The company is the sponsor of the clinical trials evaluating the drug in neuroblastoma and other solid tumors.
Naxitamab is in Phase 2 clinical development. It is an investigational agent and has not been approved by the FDA. The clinical program includes Phase 1 and Phase 2 trials across neuroblastoma, metastatic triple-negative breast cancer, and recurrent osteosarcoma.
Naxitamab is being evaluated in several trials, including NCT07537400 in newly diagnosed high-risk neuroblastoma, NCT07027748 in relapsed or refractory neuroblastoma, NCT07011654 in metastatic triple-negative breast cancer, and NCT05489887 in newly diagnosed high-risk neuroblastoma. These studies are ongoing or not yet recruiting.
Yes, Naxitamab is also known as Hu3F8 or hu3F8. It is a humanized anti-GD2 antibody, and the name Hu3F8 With GM-CSF refers to its use in combination with granulocyte-macrophage colony stimulating factor. These alternative names refer to the same investigational drug.