Unituxin (dinutuximab) / United Therapeutics Corp, Ohara Pharma - LARVOL DELTA

Atypical hemolytic uremic Syndrome Triggered by malignancy and drug exposure: A systematic review and meta-analysis (ASH 2025) - "Tacrolimus was the mostreported drug trigger (n=6)followed by gemcitabine (n=5), vincristine (n=5), bevacizumab (n=3), carfilzomib (n=3), 6-mercaptopurine(n=2), methotrexate (n=2), and mitomycin (n=2). Aflibercept, bactrim, bleomycin, capecitabine, cisplatin, cyclophosphamide, cytarabine,dasatinib, deferasirox, dinutuximab, estarylla, ketoprofen, L-asparaginase, modakafusp alfa, PEG-asparaginase, sunitinib, syntheticpsychoactive drugs, tamoxifen, and topotecan were reported as potential triggers for aHUS in one patient each...The pooled rate of treatment with eculizumab was 74% (95% CI, 0.629-0.842, p < 0.01, I2 = 72%),and the pooled rate of renal recovery was 65% (95% CI, 0.525-0.761, p < 0.01, I2 = 55%)...AKI and hematological abnormalities in these patients should prompt an emergent work-up and treatment. Current evidenceis primarily derived from case reports, so prospective trials are necessary to establish the incidence, associations, triggers, and outcomes..."

Retrospective data • Review • Acute Kidney Injury • Acute Lymphocytic Leukemia • Anemia • Atypical Hemolytic Uremic Syndrome • B Acute Lymphoblastic Leukemia • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Complement-mediated Rare Disorders • Genito-urinary Cancer • Hematological Malignancies • Hepatocellular Cancer • Hodgkin Lymphoma • Leukemia • Lung Cancer • Lymphoma • Multiple Myeloma • Nephrology • Neuroblastoma • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Renal Disease • Solid Tumor • Thrombocytopenia • Urothelial Cancer

BI21 Intermittent and progressive pustular psoriasis during chemotherapy cycles in a toddler. (PubMed, Br J Dermatol) - "Just before his next chemotherapy cycle (cisplatin and etoposide), the rash recurred as a pruritic pustular eruption across the frontal and retroauricular scalp; skin biopsy suggested nonspecific subacute eczematous dermatitis...Topical ivermectin and ketoconazole did not help...A second biopsy was taken due to clinical suspicion of psoriasis, and 10 days of oral prednisolone was given to try to clear his skin for autologous stem cell transplantation (HSCT)...He was treated with topical calcipotriol and mometasone 0.1%, with consideration of acitretin should he not improve. Fortunately, the rash settled with topical therapy and time. After completing proton radiotherapy prior to tumour resection, he had six cycles of maintenance immunotherapy (dinutuximab) with no recurrence of the rash, despite monthly GCSF, and good cell counts, and has now completed his oncological therapy."

Journal • Atopic Dermatitis • Bone Marrow Transplantation • Contact Dermatitis • Dermatitis • Dermatology • Epstein-Barr Virus Infections • Herpes Simplex • Herpes Zoster • Immunology • Neuroblastoma • Oncology • Psoriasis • Pustular Psoriasis • Solid Tumor • Transplantation • Varicella Zoster

NANT 2021-02: Randomized MIBG With Vorinostat/Dinutuximab/Vorinostat + Dinutuximab (clinicaltrials.gov) - P2 | N=118 | Not yet recruiting | Sponsor: New Approaches to Neuroblastoma Therapy Consortium

New P2 trial • Neuroblastoma • Oncology • Solid Tumor

Investigating innate immune targeting of pediatric high grade glioma via STING immunostimulation and therapeutic anti-tumor antibodies (SNO 2025) - "We demonstrate that STING pathway components are expressed in pHGG cells and that treatment with the STING agonist ADU-S100 induces robust downstream signaling, resulting in type I interferon secretion and increased cytotoxic activity of peripheral blood mononuclear cells (PBMCs) in co-culture assays...Delivery of the anti-GD2 monoclonal antibody Dinutuximab to these tumors activates the anti-tumor effects of PBMCs. Lastly, we explore tumor modulation of the GD2 target when undergoing immune stress. These findings highlight promising therapeutic approaches for pHGG, emphasizing the potential of targeted immunotherapies and increasing our understanding of tumor response to immune pressure."

Clinical • IO biomarker • Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Oncology • Pediatrics • Solid Tumor • STING

Investigating innate immune targeting of pediatric high grade glioma via STING immunostimulation and therapeutic anti-tumor antibodies (WFNOS 2025) - "We demonstrate that STING pathway components are expressed in pHGG cells and that treatment with the STING agonist ADU-S100 induces robust downstream signaling, resulting in type I interferon secretion and increased cytotoxic activity of peripheral blood mononuclear cells (PBMCs) in co-culture assays...Delivery of the anti-GD2 monoclonal antibody Dinutuximab to these tumors activates the anti-tumor effects of PBMCs. Lastly, we explore tumor modulation of the GD2 target when undergoing immune stress. These findings highlight promising therapeutic approaches for pHGG, emphasizing the potential of targeted immunotherapies and increasing our understanding of tumor response to immune pressure."

Clinical • IO biomarker • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • High Grade Glioma • Oncology • Pediatrics • Solid Tumor • STING

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

NANT 2021-01 Phase II STING (Sequential Temozolomide, Irinotecan, NK Cells and GD2 mAb) Trial (clinicaltrials.gov) - P2 | N=62 | Recruiting | Sponsor: New Approaches to Neuroblastoma Therapy Consortium | Active, not recruiting ➔ Recruiting

Enrollment open • Neuroblastoma • Oncology • Solid Tumor

Anti-CD40 monoclonal antibody improves the efficacy of standard chemo-immunotherapy in murine neuroblastoma with macrophages playing a key role (SITC 2025) - "The current standard of care for relapsed high-risk neuroblastoma includes chemo-immunotherapy: Temozolomide, Irinotecan, and anti-GD2 antibody dinutuximab (TIG). This work suggests that aCD40 may be a good candidate to combine with standard of care for relapsed high-risk neuroblastoma in children. Additional efforts are being made to better understand macrophage metabolism and function during this 9464D-GD2 response.Ethics Approval All animal work was approved by the University of Wisconsin Institutional Animal Care and Use Committees."

IO biomarker • Preclinical • Tumor mutational burden • Brain Cancer • Neuroblastoma • Oncology • Solid Tumor • MYCN • TMB

Targeting Osteosarcoma by ex-vivo Expanded NK Cells in Combination with IL-15 Agonist and Anti-GD2 antibody (SITC 2025) - "Baldrick's Foundation, Pediatric Cancer Research Foundation, Children's Cancer Fund. We thank Nektar Therapeutics for generously providing NKTR-255.Ethics Approval All animal experiments were approved by the Institutional Animal Care and Use Committee at New York Medical College (Protocol #15112) and performed in accordance with the ethical standards of the institutional research committee.Abstract 310 Figure 1Request permissionsExpanded NK cells combined with dinutuximab and NKTR-255 significantly enhanced NK cytotoxicity in vitro (A and B), decreased tumor growth (C) and improved animal survival (D) in OS xenograft mouse model"

Combination therapy • Preclinical • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CD8 • IFNG • IL15 • IL2

Reprogramming the Tumor Microenvironment with Copper Chelators to Enhance Immunotherapy in Mesothelioma (IMIG 2025) - "Given their established safety profile and clinical use in childhood disorders, Cu chelators such as Trientine (TETA) represent a promising therapy to combine with immune checkpoint blockade (ICB) for mesothelioma. Ongoing phase I/II trials are evaluating Cu chelators in combination with anti-PD-1 (Pembrolizumab) and chemotherapy in breast cancer, or in combination with anti-GD2 (Dinutuximab)in neuroblastoma. These findings provide a strong rationale to assess the safety and feasibility of combining TETA with dual ICB (Ipilimumab/Nivolumab) in patients with mesothelioma."

Biomarker • IO biomarker • Tumor microenvironment • Breast Cancer • Gastric Cancer • Lung Cancer • Mesothelioma • Neuroblastoma • Oncology • Solid Tumor • CD8 • PD-L1

Revenues (United Therapeutics Press Release) - "The decrease in Unituxin revenues resulted primarily from a decrease in quantities sold, partially offset by a price increase."

Commercial • Neuroblastoma

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

KETAMINE BASED MULTIMODAL PAIN MANAGEMENT FOR DINUTUXIMAB INDUCED PAIN: A CASE SERIES (SIOP 2025) - "A recently published case series reported average daily morphine dosing of 0.448 mg/kg/day...Our institution has adopted a multimodal analgesia regimen utilizing a ketamine infusion with scheduled acetaminophen, ketorolac, gabapentin and hydromorphone as needed... Our mulitmodal pain regimen allows for much lower doses of opioids in pediatric patients undergoing dinutuximab infusions. There have been minimal side effects with our ketamine based protocol and we have not observed any adverse effects requiring discontinuation of the ketamine infusion. A randomized trial designed to directly compare pain scores and opioid consumption could further help to guide treatment of dinutuximab infusion related pain in pediatric patients."

Clinical • Anesthesia • Neuralgia • Neuroblastoma • Pain • Pediatrics • Solid Tumor

RETROSPECTIVE ANALYSIS OF CHILDREN WITH CANCER AND BLOOD DISORDERS REQUIRING MEDICAL EVACUATION DURING THE PROTRACTED WAR IN UKRAINE (SIOP 2025) - "Among patients evacuated to access specific cancer medication, the majority required the immunotherapeutic Blinatumomab (36.0% in 2023, 54.2% in 2024) or Dinutuximab (28.0% in 2023, 20.8% in 2024). During the protracted crisis in Ukraine, lack of access to specific cancer medication is becoming an increasing challenge and forces medical evacuations for patients who could otherwise be treated locally. This emphasizes the urgent need for strategies to maintain access to medication for childhood cancer patients in crisis regions."

Retrospective data • Oncology • Palliative care

RETROSPECTIVE EVALUATION OF THE ADMINISTRATION OF DINUTUXIMAB VIA AN ELASTOMERIC PUMP: INSIGHTS AND LESSONS LEARNED FROM A NURSING PRACTICE PERSPECTIVE (SIOP 2025) - "Elastomeric pumps were introduced in our pediatric hemato-oncology department for the administration of dinutuximab-beta (DB) in high-risk neuroblastoma patients. Close monitoring of DB-elastomer pumps at home ensures infusion safety and effectiveness. Quality of care improved through iterative problem-solving, adaptation and implementation of a systematic protocol. Key factors include: sensor fixation, catheter accessibility and knowledge by healthcare professionals."

Retrospective data • Neuroblastoma • Pediatrics • Solid Tumor

NEUROTOXICITY FROM DINUTUXIMAB: INCIDENCE, PRESENTATION, AND NURSING ACTIONS (SIOP 2025) - "Findings underscore the need for targeted neurologic assessment and structured nursing interventions. These findings can inform the development of clinical practice guidelines; however prospective research is needed to evaluate intervention effectiveness and long-term outcomes."

Neuroblastoma • Pediatrics • Solid Tumor

The glycogen synthase kinase-3β inhibitor 9-ING-41 in combination with chemoimmunotherapy provides long-term survival in the Th-MYCN mouse model (AACR-NCI-EORTC 2025) - P1 | " Th-MYCN mice relapsed within 60 days following treatment with 2 consecutive daily doses of temozolomide/irinotecan (TEMIRI) or cyclophosphamide/topotecan (CYCLO/TOPO), in addition to 15µg 14G2a on day 1 and day 5. Pharmacokinetics of radiolabelled 14G2a confirmed that this regimen resulted in equivalent 14G2a serum levels in tumor-bearing Th-MYCN mice as observed for Dinutuximab in neuroblastoma patients... 9-ING-41 in combination with chemoimmunotherapy is highly potent, resulting in long-term tumor-free survival in the Th-MYCN mouse model of neuroblastoma. Our data suggests that 9-ING-41 at least in part works through modulating anti-tumour immunity, and we are currently investigating this further."

Combination therapy • Preclinical • Neuroblastoma • Oncology • Solid Tumor • MYCN

ANBL19P1: Treatment With Dinutuximab, Sargramostim (GM-CSF), and Isotretinoin in Combination With Irinotecan and Temozolomide After Intensive Therapy for People With High-Risk Neuroblastoma (NBL) (clinicaltrials.gov) - P2 | N=41 | Active, not recruiting | Sponsor: Children's Oncology Group | Trial completion date: Sep 2025 ➔ Sep 2027

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

…Unituxin revenues fell 22% to $47.9 million. (Investing.com)

Sales • Neuroblastoma • Neuroendocrine Tumor

NCI-2018-03732: Dinutuximab, Sargramostim, and Combination Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma (clinicaltrials.gov) - P2 | N=42 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Sep 2025 ➔ Sep 2026

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

A Study of Abemaciclib (LY2835219) in Combination With Other Anti-Cancer Treatments in Children and Young Adult Participants With Solid Tumors, Including Neuroblastoma (clinicaltrials.gov) - P1/2 | N=47 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ Aug 2025

Trial completion • Trial completion date • Neuroblastoma • Oncology • Pediatrics • Solid Tumor

Immunotherapy in Neuroblastoma: Mini-Review of Novel Directions and Challenges. (PubMed, J Pediatr Hematol Oncol) - "Immunotherapy further improved survival rates that included monoclonal antibody (Anti-GD2 MoAb/Dinutuximab) and cytokines (ie, IL-2 and GM-CSF, [33-37])...This allowed them to produce a CAR that targets a tumor-specific antigen. Following preparatory chemotherapy, the CAR T cell product is administered into the patient."

IO biomarker • Journal • Bone Marrow Transplantation • Neuroblastoma • Oncology • Pediatrics • Solid Tumor • Transplantation • CSF2 • IL2

Dinutuximab-associated neurotoxicity: A 5-year retrospective analysis of incidence, presentation, risk factors, and nursing intervention (APHON 2025) - No abstract available

Retrospective data

Ganglioside Profiling Uncovers Distinct Patterns in High-Risk Neuroblastoma. (PubMed, Int J Mol Sci) - "Profile C was found only in cell lines of the mesenchymal subtype. These findings support further investigation of GG composition and associated enzyme expression as potential biomarkers for risk stratification and treatment response in NBL."

Biomarker • Journal • Neuroblastoma • Oncology • Solid Tumor • B4GALNT1