Danyelza (naxitamab-gqgk) / SERB Pharmaceuticals, Takeda, SciClone, Nobelpharma, INPHARMUS - LARVOL DELTA

A phase II trial of naxitamab plus stepped-up dosing of GM-CSF for patients with high-risk neuroblastoma in second or later complete remission. (PubMed, Int J Cancer) - P1/2 | "Naxitamb+GM-CSF is a good option to consolidate post-relapse CR of HR-NB. The encouraging long-term outcome cannot be attributed solely to naxitamab+GM-CSF given post-protocol therapies."

Journal • P2 data • Neuroblastoma • Oncology • Solid Tumor • CSF2 • MYCN

Identification and Pre-clinical Evaluation of a Novel GD2 Antibody-Drug Conjugate for Solid Tumors in Children and Adults. (PubMed, Mol Cancer Ther) - "The humanized version, hCA450-21, displayed higher cell-binding activity than ch14.18 and Hu3F8, along with excellent specificity and internalization capacity...The crystal structure of the hCA450-21.1 Fab-GD2 complex was resolved at 1.69 Å, revealing unique hydrogen bonds and hydrophobic interactions that contribute to its high specificity and affinity. Overall, the novel hCA450-21.1-LA-68B ADC shows preclinical efficacy and reduced toxicity, particularly neurotoxicity, indicating potential as a safer and more effective therapy for GD2-positive pediatric and adult tumors."

Journal • Preclinical • Brain Cancer • Breast Cancer • Glioblastoma • Melanoma • Neuroblastoma • Oncology • Pediatrics • Solid Tumor

The Price of Survival: Global Inequities in Anti-GD2 Immunotherapy for Neuroblastoma. (PubMed, Pediatr Blood Cancer) - "Global access to anti-GD2 therapy is highly unequal. Strategic measures, including negotiations for reduced drug costs, research-based access, and WHO Essential Medicines List inclusion, could help address these disparities."

Journal • Neuroblastoma • Oncology • Solid Tumor

Naxitamab with novel scheduling and stepped-up dosing of GM-CSF plus vaccine, but no myeloablative therapy for patients with high-risk neuroblastoma in first complete remission. (PubMed, Int J Cancer) - "EFS/OS rates at 24 months were 88%/95% and at 36 months were 80%/95%. Naxitamab + nGM-CSF is a good option to consolidate first CR of HR-NB patients, including those who did not undergo MAT."

Journal • Hematological Disorders • Neuroblastoma • Oncology • Solid Tumor • CSF2

Study 12-230: Combination Therapy of Antibody Hu3F8 With Granulocyte- Macrophage Colony Stimulating Factor (GM-CSF) in Patients With Relapsed/Refractory High-Risk Neuroblastoma (clinicaltrials.gov) - P1/2 | N=186 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Neuroblastoma • Oncology • Solid Tumor • CSF2 • MYC • MYCN

Utilization of Neutrophil Elastase Tetrapeptide Substrate as a Linker Agent for Anti-GD2 Antibody Drug Conjugates. (PubMed, Bioconjug Chem) - "In M21 melanoma mouse models, Hu3F8-BMOA-MMAE achieved an obvious tumor inhibition rate compared to the control. These findings demonstrate that utilizing a neutrophil elastase tetrapeptide substrate as a linker in anti-GD2 ADCs is a potential strategy for the therapy of GD2-positive tumors."

Journal • Melanoma • Oncology • Solid Tumor • ELANE

PET Imaging of Solid Tumors Using 124I-Humanized 3F8: A Pilot Study (clinicaltrials.gov) - P=N/A | N=7 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2025 ➔ Nov 2026 | Trial primary completion date: Nov 2025 ➔ Nov 2026

Trial completion date • Trial primary completion date • Melanoma • Neuroblastoma • Oncology • Sarcoma • Solid Tumor • MYCN

Naxitamab plus stepped-up dosing of granulocyte-macrophage colony-stimulating factor for primary refractory high-risk neuroblastoma: results of a phase I/II trial. (PubMed, J Hematol Oncol) - P1/2 | "Naxitamb + GM-CSF is an attractive option for primary refractory osteomedullary disease, including in patients with a high disease burden."

Journal • P1/2 data • Neuroblastoma • Oncology • Solid Tumor • CSF2

Development of [89Zr]Zr-DFO-hu3F8 and [225Ac]Ac-DOTA-hu3F8 Theranostic Pairs Targeting GD2 in Neuroblastomas. (PubMed, J Med Chem) - "A single dose of [225Ac]Ac-DOTA-hu3F8 treatment significantly suppressed tumor growth, with most tumors (4/5) achieving complete remission at medium and high doses (11.1 and 18.5 kBq). Overall, our findings demonstrate that alpha-targeted therapy based on hu3F8 holds significant potential as a promising curative treatment strategy for NBL."

Journal • Neuroblastoma • Oncology • Solid Tumor

Ganglioside therapy in cancer molecular insights and therapeutic opportunities. (PubMed, Discov Oncol) - P2, P3 | "Dinutuximab, approved for high-risk neuroblastoma, improved event-free survival when combined with cytokines with standard therapy alone (NCT00026312). Similarly, Naxitamab, in combination with GM-CSF, achieved an overall response rate in relapsed/refractory neuroblastoma (NCT03363373)...Additionally, Racotumomab (anti-NeuGcGM3) demonstrated a survival benefit in advanced non-small cell lung cancer, extending median overall survival compared to placebo (NCT01240447). Despite these advances, challenges remain in improving patient selection, reducing off-target toxicities such as neuropathic pain, and addressing resistance mechanisms. This review examines the latest developments in ganglioside-mediated cancer therapy, emphasizing current clinical outcomes, highlighting the need for more precise targeting approaches, and exploring rational combination strategies to enhance therapeutic efficacy."

IO biomarker • Journal • Review • Lung Cancer • Neuralgia • Neuroblastoma • Non Small Cell Lung Cancer • Oncology • Pain • Sarcoma • Solid Tumor • CSF2

A FIRST-IN-HUMAN PHASE 1, MULTICENTER, OPEN-LABEL STUDY OF M3554, A NOVEL ANTI-GD2 ANTIBODY-DRUG CONJUGATE, IN PATIENTS WITH ADVANCED SOLID TUMORS (CTOS 2025) - P1 | "GD2 is a clinically validated target in pediatric neuroblastoma, however, currently approved anti-GD2 antibodies (e.g., dinutuximab, naxitamab) are associated with severe pain adverse events (AEs), likely due to Fcγ receptor-mediated immune activation via antibody dependent cellular cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC). N/A"

Clinical • First-in-human • Metastases • P1 data • Brain Cancer • Glioblastoma • Neuroblastoma • Oncology • Osteosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • TOP1

Targeting GD2 with naxitamab overcomes GD3 synthase-driven immune suppression in triple-negative breast cancer. (PubMed, NPJ Breast Cancer) - "Moreover, naxitamab treatment enhanced macrophage-mediated phagocytosis and NK cell-mediated cytotoxicity and inhibited tumor growth in a TNBC patient-derived xenograft model. Our findings highlight GD3S-driven immunosuppression and provide proof-of-concept that naxitamab, with activated immune cells, reverses this effect, revealing its therapeutic potential in treating GD2+ BC."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

SAFETY OF NAXITAMAB+GM-CSF IN COMBINATION WITH INDUCTION CHEMOTHERAPY IN HIGH-RISK NEUROBLASTOMA (SIOP 2025) - P2 | "No new safety concerns have emerged. The safety profile of naxitamab when combined with induction chemotherapy was found to be manageable and acceptable."

Clinical • Combination therapy • Hypertension • Hypotension • Neuroblastoma • Pulmonary Disease • Solid Tumor • CSF2

USING THE STEP UP PROTOCOL WITH NAXITAMAB ADMINISTRATION IN A RELAPSED/REFRACTORY NEUROBLASTOMA PATIENT WITH ANAPHYLAXIS TO DINUTUXIMAB (SIOP 2025) - "Pain plan consisted of low dose ketamine infusion and fentanyl boluses directed by the pain team. Naxitamab "step-up" protocol is an option for children who have had anaphylaxis to dinutuximab in order to continue anti-GD2 therapy in a challenging disease. This experience shows retry with another anti-GD2 therapy is possible. Naxitamab can be safely administered with complex supportive care measures and in collaboration with intensive care and pain team."

Clinical • Neuroblastoma • Solid Tumor

NRG3/ERBB4 ENHANCES EFFICACY OF CHEMOTHERAPY COMBINED WITH IMMUNOTHERAPY IN HIGH-RISK NEUROBLASTOMA (SIOP 2025) - "Moreover, chemotherapy-inhibited NRG3 and ERBB4 expression levels were reversely elevated by 3F8 (Naxitamab, CI cohort) in the induction phase, and positively correlated with NB-reactive immune response... Collectively, we generated detailed NB-associated secrete patterns under different risks, and clarified their possible network with immune effector cells in pre-treatment, chemotherapy and chemo-immunotherapy of NB. These data elucidate a novel mechanism of 3F8, and an important step forward in understanding tumor-effector cell interaction, specifically in chemo-immunotherapy NB patients. Further, we also provide candidates beneficial for the development of adjuvant treatments, and inform more refined combination strategies to overcome immune resistance."

Clinical • IO biomarker • Neuroblastoma • Solid Tumor • ERBB4 • GNLY • GZMB • NRG3 • SLIT2

EVALUATION OF NEW CHEMO-IMMUNOTHERAPY COMBINATIONS AFTER THERAPEUTIC FAILURE WITH IRINOTECAN-TEMOZOLAMIDE AND ANTI-GD2 IN REFRACTORY OR RELAPSED NEUROBLASTOMA (SIOP 2025) - "This study aimed to evaluate the response to switching the chemotherapy backbone to cyclophosphamide-topotecan in combination with anti-GD2 (C/T/anti-GD2) in patients who failed a first salvage strategy with irinotecan, temozolomide, and anti-GD2 (I/T/anti-GD2). This retrospective study analyzed patients with r/r HR-NB treated between 2020 and 2024, who received cyclophosphamide (250 mg/m², D1-D5) and topotecan (0.75 mg/m², D1-D5), combined with either dinutuximab beta (35 mg/m², D1-D7, continuous infusion) or naxitamab (2.25 mg/m²/day, D2, D4, D9, D11), after prior treatment with I/T/anti-GD2... Switching to C/T/anti-GD2 after failure of I/T/anti-GD2 achieved disease control in a substantial proportion of patients. Outcomes were encouraging considering the high-risk, heavily pretreated population. However, long-term durability remains challenging, underscoring the need for alternative strategies to achieve sustained responses."

Cardiovascular • Dermatology • Hematological Disorders • Hypertension • Immunology • Neuroblastoma • Solid Tumor • Urticaria

DINUTUXIMAB BETA VERSUS NAXITAMAB IN RELAPSED/REFRACTORY NEUROBLASTOMA PATIENTS WITH STABLE DISEASE, MINOR RESPONSE OR PARTIAL RESPONSE AND DISEASE IN BONE OR BONE MARROW (SIOP 2025) - "In this type of analysis, data suggest that dinutuximab beta in patients with neuroblastoma in bone or bone marrow with incomplete or no response to prior therapy mediates greater response rate and event-free survival compared to naxitamab. The benefit of DB is greater when DB is used without IL-2."

Clinical • Neuroblastoma • Solid Tumor • CSF2 • MYCN

NURSING INTERVENTIONS IN THE MANAGEMENT OF ADVERSE EVENTS DURING THE ADMINISTRATION OF NAXITAMAB IN PEDIATRIC PATIENTS WITH HIGH-RISK NEUROBLASTOMA IN A TERTIARY HOSPITAL IN MEXICO. (SIOP 2025) - "Naxitamab requires a solid infusion equipment to reduce AE's, with the nursing interventions the rapid management of AE's, reduction of hospital stay and creation of instruments, the AE's were similar to those reported in the literature, in Mexico despite not having Ketamine, the use of Buprenorphine had excellent results."

Adverse events • Clinical • Cardiovascular • Neuroblastoma • Pediatrics • Solid Tumor

AFFINITY AFFECTS THE FUNCTIONAL POTENCY OF ANTI-GD2 ANTIBODIES DINUTUXIMAB BETA AND NAXITAMAB BY TARGET-MEDIATED DRUG DISPOSITION (TMDD). (SIOP 2025) - "Finally, sGD2 impaired NAXI-mediated ADCC to a significantly greater extent than DB-mediated ADCC. Conclusions DB has a higher ADCC potency over NAXI at clinically relevant concentrations, attributed to stronger TMDD effects of NAXI compared to DB."

Neuroblastoma • Solid Tumor

IMPROVED OVERALL RESPONSE OF STAGE M HIGH-RISK NEUROBLASTOMA (HR-NB) TREATED WITH NAXITAMAB AND CHEMOTHERAPY IN INDUCTION PHASE (SIOP 2025) - P | "The EOI response of CR was 85.7%, PR or better reached 100%. Conclusions Incorporation of naxitamab into the induction phase of HR-NB treatment effectively improve the early ORR and EOI response, decrease tumor volume and IDRFs."

Neuroblastoma • Solid Tumor • CSF2 • MYCN

Study of Naxitamab and Sacituzumab Govitecan in Patients With Metastatic Triple-negative Breast Cancer (TNBC) (clinicaltrials.gov) - P1/2 | N=31 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Nov 2030 ➔ Jul 2030

Trial completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Study of Naxitamab and Sacituzumab Govitecan in Patients With Metastatic Triple-negative Breast Cancer (TNBC) (clinicaltrials.gov) - P1/2 | N=31 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

A pharmacological and clinical profile of Naxitamab for the treatment of high-risk neuroblastoma. (PubMed, Expert Rev Clin Pharmacol) - "Ongoing clinical studies and expanded global use continue to evaluate its safety and efficacy, to optimize its integration with standard care, and to fully exploit its therapeutic potential. Advances in protein engineering can further extend the utility of anti-GD2 mAbs, enabling the creation of radioimmunoconjugates, novel bispecific antibodies, and pre-targeting strategies, offering potent tumor selectivity while mitigating off-target toxicity."

Journal • Review • Neuroblastoma • Oncology • Pediatrics • Solid Tumor • CSF2

A Study of the Effect of Hu3F8/GM-CSF Immunotherapy Plus Isotretinoin in Patients in First Remission of High-Risk Neuroblastoma (clinicaltrials.gov) - P2 | N=59 | Completed | Sponsor: Memorial Sloan Kettering Cancer Center | Active, not recruiting ➔ Completed | Trial completion date: Jun 2026 ➔ Sep 2025 | Trial primary completion date: Jun 2026 ➔ Sep 2025

Trial completion • Trial completion date • Trial primary completion date • Neuroblastoma • Oncology • Solid Tumor • MYCN

Humanized Monoclonal Antibody 3F8 (Hu3F8) With Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in the Treatment of Recurrent Osteosarcoma (clinicaltrials.gov) - P2 | N=46 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Jul 2025 ➔ Jul 2026 | Trial primary completion date: Jul 2025 ➔ Jul 2026

Trial completion date • Trial primary completion date • Oncology • Osteosarcoma • Sarcoma • Solid Tumor