Qarziba (dinutuximab beta) / BeOne Medicines, Recordati, Ligand - LARVOL DELTA

THE CLINICAL COURSE OF HAPLOHSCT + DINUTUXIMAB BETA IMMUNOTHERAPY IN POLISH CHILDREN WITH RELAPSING NEUROBLASTOMA (EBMT 2026) - "The procedure included FluMelTT ( Fludarabin 4 x 40 mg/m2 BSA, Thiotepa 10 mg/kg body weight, melphalan 2 x 70 mg/m2 BSA ) conditioning + ATG Grafalon in dose 30mg/kg with immunosuppresion – mycophenolate of mofetil depending of the T cell level in transplant (600-1200 mg/ kg body weight ) and G-CSF support from +4 day after HSCT...3 patients received 131I MIBG therapy 2-3 weeks before transplantation... HaploHSCT with dinutuximab beta therapy seems to be encouraging method of treatment for children with relapsing neuroblastoma, connecting chemotherapy and immunotherapy. This method seems to be well tolerated with no serious toxicities. Although due to posiible toxicities of the method, the patients should be carefully selected to this method of theatment."

Clinical • Acute Graft versus Host Disease • Bone Marrow Transplantation • Dental Disorders • Graft versus Host Disease • Hematological Disorders • Immunology • Infectious Disease • Neuroblastoma • Septic Shock • Solid Tumor • Stomatitis

IMMUNE CELL THERAPY AFTER TCRΑΒ⁺/CD19⁺-DEPLETED HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION IN RELAPSED HIGH-RISK NEUROBLASTOMA: A PHASE 2 SINGLE-CENTER STUDY (EBMT 2026) - "Two patients are disease-free at 1 and 2.7 years after haplo-HSCT, respectively; two experienced local relapse at 10 and 11 months after haplo-HSCT and started local radiotherapy plus temozolomide, which is ongoing; and one patient developed a local relapse 13 months after haplo-HSCT and achieved a second complete remission following local radiotherapy, topotecan, and consolidation with anti-GD2 CAR-T therapy, remaining stable 14 months after relapse. Preliminary data demonstrate the feasibility and safety of haplo-HSCT followed by immunotherapy with dinutuximab beta and NK cell infusions in relapsed HR neuroblastoma. This approach shows promise for improving immune control of disease. Long-term efficacy will be assessed with a larger cohort and extended follow-up."

Clinical • Immune cell • P2 data • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Neuroblastoma • Solid Tumor • Transplant Rejection • Transplantation

THE CLINICAL COURSE OF HAPLOHSCT + DINUTUXIMAB BETA IMMUNOTHERAPY IN POLISH CHILDREN WITH RELAPSING NEUROBLASTOMA (EBMT 2026) - "The procedure included FluMelTT ( Fludarabin 4 x 40 mg/m2 BSA, Thiotepa 10 mg/kg body weight, melphalan 2 x 70 mg/m2 BSA ) conditioning + ATG Grafalon in dose 30mg/kg with immunosuppresion – mycophenolate of mofetil depending of the T cell level in transplant (600-1200 mg/ kg body weight ) and G-CSF support from +4 day after HSCT...3 patients received 131I MIBG therapy 2-3 weeks before transplantation... HaploHSCT with dinutuximab beta therapy seems to be encouraging method of treatment for children with relapsing neuroblastoma, connecting chemotherapy and immunotherapy. This method seems to be well tolerated with no serious toxicities. Although due to posiible toxicities of the method, the patients should be carefully selected to this method of theatment."

Clinical • Acute Graft versus Host Disease • Bone Marrow Transplantation • Dental Disorders • Graft versus Host Disease • Hematological Disorders • Immunology • Infectious Disease • Neuroblastoma • Septic Shock • Solid Tumor • Stomatitis

NANT: Lenalidomide and Dinutuximab With or Without Isotretinoin in Treating Younger Patients With Refractory or Recurrent Neuroblastoma (clinicaltrials.gov) - P1 | N=27 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2026 ➔ Mar 2027

Trial completion date • Neuroblastoma • Oncology • Solid Tumor

Isotretinoin With or Without Dinutuximab, Aldesleukin, and Sargramostim Following Stem Cell Transplant in Treating Patients With Neuroblastoma (clinicaltrials.gov) - P3 | N=1449 | Completed | Sponsor: National Cancer Institute (NCI) | Active, not recruiting ➔ Completed

Trial completion • Neuroblastoma • Oncology • Solid Tumor • Transplantation

Testing the Addition of Iberdomide to Therapy in People With Neuroblastoma That Has Come Back, Not Responded to Treatment, or Gotten Worse (clinicaltrials.gov) - P1/2 | N=76 | Not yet recruiting | Sponsor: National Cancer Institute (NCI)

New P1/2 trial • Ganglioneuroblastoma • Neuroblastoma • Oncology • Solid Tumor

BEACON: Activity Study of Bevacizumab With Temozolomide ± Irinotecan for Neuroblastoma in Children (clinicaltrials.gov) - P2b | N=224 | Recruiting | Sponsor: University of Birmingham | N=160 ➔ 224 | Trial completion date: Jan 2022 ➔ Jul 2026 | Trial primary completion date: Oct 2020 ➔ Jul 2021

Enrollment change • Trial completion date • Trial primary completion date • Neuroblastoma • Oncology • Solid Tumor

BEACON: Activity Study of Bevacizumab With Temozolomide ± Irinotecan for Neuroblastoma in Children (clinicaltrials.gov) - P2b | N=160 | Recruiting | Sponsor: University of Birmingham | Trial primary completion date: Jul 2017 ➔ Jul 2018

Trial primary completion date • Neuroblastoma • Oncology • Solid Tumor

BEACON: Activity Study of Bevacizumab With Temozolomide ± Irinotecan for Neuroblastoma in Children (clinicaltrials.gov) - P2b | N=160 | Recruiting | Sponsor: University of Birmingham | N=120 ➔ 160 | Trial primary completion date: Jan 2017 ➔ Jul 2017

Enrollment change • Trial primary completion date • Neuroblastoma • Oncology • Solid Tumor

BEACON: Activity Study of Bevacizumab With Temozolomide ± Irinotecan for Neuroblastoma in Children (clinicaltrials.gov) - P2b | N=160 | Recruiting | Sponsor: University of Birmingham | Trial primary completion date: Sep 2018 ➔ Oct 2020

Trial primary completion date • Neuroblastoma • Oncology • Solid Tumor

BEACON: Activity Study of Bevacizumab With Temozolomide ± Irinotecan for Neuroblastoma in Children (clinicaltrials.gov) - P2b | N=225 | Active, not recruiting | Sponsor: University of Birmingham | Trial primary completion date: Dec 2021 ➔ Aug 2021

Trial primary completion date • Neuroblastoma • Oncology • Solid Tumor

BEACON: Activity Study of Bevacizumab With Temozolomide ± Irinotecan for Neuroblastoma in Children (clinicaltrials.gov) - P2 | N=225 | Active, not recruiting | Sponsor: University of Birmingham | Phase classification: P2b ➔ P2 | Trial completion date: Dec 2026 ➔ Feb 2026

Phase classification • Trial completion date • Neuroblastoma • Oncology • Solid Tumor

BEACON: Activity Study of Bevacizumab With Temozolomide ± Irinotecan for Neuroblastoma in Children (clinicaltrials.gov) - P2b | N=225 | Active, not recruiting | Sponsor: University of Birmingham | Recruiting ➔ Active, not recruiting | Trial completion date: Jul 2026 ➔ Dec 2026 | Trial primary completion date: Jul 2021 ➔ Dec 2021

Enrollment closed • Trial completion date • Trial primary completion date • Neuroblastoma • Oncology • Solid Tumor

ChIm-NB-PL: Immunotherapy with dinutuximab beta in combination with chemotherapy for the treatment of patients with primary neuroblastoma refractory to standard therapy and with relapsed or progressive disease. (clinicaltrialsregister.eu) - P2/3 | N=28 | Active, not recruiting | Sponsor: Uniwersytet Jagiellonski Collegium Medicum | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Neuroblastoma • Oncology • Solid Tumor

Efficacy and safety of dinutuximab beta combined with GM-CSF and isotretinoin ± chemotherapy as first-line maintenance treatment for pediatric high-risk neuroblastoma in China. (PubMed, Front Oncol) - "Real-world evidence on dinutuximab beta for high-risk neuroblastoma (NB) in the Chinese pediatric patients remains limited. Patients treated with prior ASCT or combined with chemotherapy showed trends toward improved response rates and survival outcomes, although optimal treatment regimens required further investigation. AEs are generally manageable, and the use of standardized pain assessment combined with multimodal analgesia has enabled a substantial reduction in morphine exposure."

Journal • Febrile Neutropenia • Hematological Disorders • Neuroblastoma • Neutropenia • Oncology • Pain • Pediatrics • Solid Tumor • Thrombocytopenia • Transplantation • CSF2

Irinotecan Hydrochloride, Temozolomide, and Dinutuximab With or Without Eflornithine in Treating Patients With Relapsed or Refractory Neuroblastoma (clinicaltrials.gov) - P2 | N=94 | Active, not recruiting | Sponsor: Children's Oncology Group | Trial completion date: Apr 2026 ➔ Mar 2029

Trial completion date • Neuroblastoma • Oncology • Solid Tumor

Dinutuximab beta versus historical controls in the treatment of relapsed neuroblastoma: unadjusted and adjusted indirect comparisons. (PubMed, Front Oncol) - "All sensitivity unadjusted and adjusted comparisons supported the results of the base-case analysis. Dinutuximab beta significantly prolonged OS compared to historical control cohorts not treated with dB in both unadjusted and adjusted indirect comparisons."

Journal • Neuroblastoma • Oncology • Solid Tumor • IL2

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

NB-NK-2026: Chemoimmunotherapy Combined With Autologous NK Cell Therapy for Pediatric Patients With Refractory and Relapsed High-Risk Neuroblastoma and Ganglioneuroblastoma (clinicaltrials.gov) - P3 | N=5 | Recruiting | Sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology

New P3 trial • Ganglioneuroblastoma • Neuroblastoma • Oncology • Pediatrics • Solid Tumor

Dinutuximab Beta Anaphylaxis: Successful Desensitization Using a One-Bag Protocol in a Pediatric Case. (PubMed, Pediatr Blood Cancer) - No abstract available

Journal • Pediatrics

Anti-GD2 Antibody Dinutuximab Beta and Low-Dose Interleukin 2 After Haploidentical Stem-Cell Transplantation in Patients With Relapsed Neuroblastoma: A Multicenter, Phase I/II Trial. (PubMed, J Clin Oncol) - "DB therapy after haplo-SCT in patients with rHR-NB is feasible, with low risk of inducing GvHD, and results in long-term remissions likely attributable to increased antineuroblastoma activity by donor-derived effector cells."

Journal • P1/2 data • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • CNS Tumor • Graft versus Host Disease • Immunology • Neuroblastoma • Neuroendocrine Tumor • Oncology • Solid Tumor • Transplantation • IL2

Dinutuximab beta effectively treats Ewing sarcoma when combined with chemotherapy. (PubMed, iScience) - "The combination therapy with doxorubicin demonstrated superior efficacy compared to monotherapy, with enhanced tumor suppression (86%; p = 0.0009) and an extension of survival rate (146%; p = 0.000025). This study showed that dinutuximab beta, particularly in combination with standard chemotherapy, offers a promising approach to improve outcomes for high-risk Ewing sarcoma patients, providing a more effective alternative to current treatments."

Journal • Ewing Sarcoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

BEACON2: A Multi-Arm, Platform Trial For Relapsed Neuroblastoma (clinicaltrials.gov) - P1/2 | N=160 | Recruiting | Sponsor: University of Birmingham

New P1/2 trial • Neuroblastoma • Oncology • Solid Tumor

Phase II Study of Chidamide-Dinutuximab Beta-Irinotecan-Temozolomide for Refractory/Relapsed Neuroblastoma in Children (clinicaltrials.gov) - P2 | N=27 | Not yet recruiting | Sponsor: Tianjin Medical University Cancer Institute and Hospital

New P2 trial • Neuroblastoma • Oncology • Solid Tumor

Extended cycles of anti-GD2 antibody dinutuximab beta treatment combined with chemotherapy in patients with relapsed or refractory neuroblastoma: A retrospective study. (PubMed, Oncol Lett) - "In this single-center retrospective study, children with a median age 5.1 years (range, 2.0-11.1 years) with R/R HR-NB who were treated with >5 cycles of dinutuximab beta (10 mg/m2/day for 10-days per 35-day cycle), granulocyte-macrophage colony-stimulating factor (GM-CSF) and isotretinoin, plus chemotherapy, were included. No immune-related deaths occurred. Overall, cycles beyond the standard 5 cycles of dinutuximab beta with chemoimmunotherapy were effective and tolerable in pediatric patients with R/R HR-NB, demonstrating improved response and survival outcomes."

Journal • Retrospective data • Hematological Disorders • Infectious Disease • Leukopenia • Neuroblastoma • Neutropenia • Oncology • Pain • Pediatrics • Solid Tumor • CSF2