Unituxin (dinutuximab)

P1/2, N=117, Active, not recruiting, Eli Lilly and Company | Recruiting --> Active, not recruiting

P3, N=478, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

P1, N=82, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting

P3, N=1449, Active, not recruiting, National Cancer Institute (NCI)

P2, N=24, Completed, Fundació Sant Joan de Déu | Unknown status --> Completed

P2, N=42, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Sep 2024

Moreover, ex vivo culture with IL-7+IL-15+IL-21 could favor CAR-T products with a longer persistence in the host. Our strategy may complement the current use of Dinutuximab in treating NB through its combination with a targeted CAR-T cell approach.

P1, N=27, Active, not recruiting, National Cancer Institute (NCI)

P2, N=95, Active, not recruiting, Children's Oncology Group | Trial completion date: Jun 2024 --> Mar 2025 | Trial primary completion date: Jun 2024 --> Mar 2025

P1/2, N=31, Recruiting, Nationwide Children's Hospital | Trial primary completion date: Dec 2023 --> Dec 2024

P1/2, N=117, Recruiting, Eli Lilly and Company | Phase classification: P1b/2 --> P1/2 | Trial primary completion date: Jun 2027 --> May 2028

P2, N=153, Active, not recruiting, St. Jude Children's Research Hospital | Trial completion date: Dec 2023 --> Dec 2024

P1, N=82, Suspended, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Dec 2032 | Trial primary completion date: Jun 2026 --> Dec 2032

P1, N=24, Recruiting, Emory University

P3, N=478, Not yet recruiting, National Cancer Institute (NCI)

The N-803 combined with dinutuximab and exPBNK cells significantly extended the survival of NB xenografts (Chu/Cairo, et al, JITC...C021 was generated by modifying C134 to express human IL21 gene... Our data demonstrated IL15 or IL21 based novel cytokine therapy (N-803 or C021) significantly enhanced the anti-tumor efficacy of ROR1 CAR NK targeting NB in vitro and in vivo

The externally controlled analyses presented show a relapse risk reduction in patients with HRNB treated with postimmunotherapy DFMO.

P2, N=41, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed

P1, N=13, Active, not recruiting, New Approaches to Neuroblastoma Therapy Consortium | Trial completion date: Sep 2023 --> Sep 2024 | Trial primary completion date: Sep 2023 --> Sep 2024

We observed excellent outcomes in 99 pts treated with proton radiotherapy for HR-NBL from 2010 through 2021, with 81% of patients alive and 92% free of LR. Our data suggest that LR is rare after GTR and 21.6 Gy, and uncommon among pts with STR treated with 36 Gy. A small number of pts received 21.6 Gy after STR, however, this experience suggests that a subset of pts with RD may require RT dose > 21.6 Gy. Further work is required to further characterize individual management of PS in pts with HR-NBL with regard to extent of RD and biologic disease features.

P2, N=34, Active, not recruiting, Children's Oncology Group | Trial completion date: Dec 2023 --> Sep 2024 | Trial primary completion date: Dec 2023 --> Jun 2023

The EOI response of PR or better in the evaluable cohort was 96%. Dinutuximab was well tolerated with all Induction cycles, demonstrated an encouraging EOI response rate, and should be evaluated in a randomized study.

Results found that dinutuximab β is not a cost-effective treatment option for children with high-risk NB unless its price is significantly reduced.

Patients with relapsed neuroblastoma are often treated with immunotherapy such as the anti-GD2 antibody, dinutuximab, in combination with chemotherapy...The mechanism of ST8SIA1 suppression by YAP is independent of PRRX1 expression, a mesenchymal master transcription factor, suggesting YAP may be the downstream effector of mesenchymal GD2 resistance. These results therefore identify YAP as a therapeutic target to augment GD2 immunotherapy responses in patients with neuroblastoma.

IgA3.0 ch14.18 is a promising new therapy for neuroblastoma, showing (1) increased half-life compared to natural IgA antibodies, (2) increased protein stability enabling effortless production and purification, (3) potent CD89-mediated tumor killing in vitro by healthy subjects and patients with neuroblastoma and (4) antitumor efficacy in long-term mouse neuroblastoma models.

Daily average of IV morphine milligram equivalents (MME) and ketamine intake was calculated for each cycle of dinutuximab. Preliminary findings suggest an acceptable adverse effect profile with ketamine use as an adjunctive opioid therapy to relieve pain in pediatric patients receiving dinutuximab infusions.

While immunotherapy for pediatric cancer has made great strides in recent decades, including the FDA approval of agents such as dinutuximab and tisgenlecleucel, these successes have rarely impacted children with pediatric central nervous system (CNS) tumors...Combinatorial strategies and future directions will be addressed. Through internationally collaborative efforts and consortia, we aim to direct this promising field of immuno-oncology to the next frontier of successful application against pediatric CNS tumors.

Our data provide a ra onale for a preclinical evalua on of IL1RAP-CAR NK/TGFbi-NK combined with NKTR-255 and dinutuximab in limi ng ES xenogra tumor growth and/or metastasis and prolonging animal survival in-vivo. Count: 400 words (Limit 400 words) This study was funded by NCI Cancer Moonshot U54 grant (CA232561-01A1).

P2, N=45, Active, not recruiting, Children's Oncology Group | Suspended --> Active, not recruiting

P2, N=45, Suspended, Children's Oncology Group | Active, not recruiting --> Suspended

We then treated established SK-N-AS control or shYAP xenografts with an 18-day course of human γδ T cells, dinutuximab, and cyclophosphamide. Pilot results show significantly extended survival in mice harboring SK-N-AS shYAP tumors.Conclusion These results support YAP regulation of GD2 expression through transcriptional suppression of GD3 synthase and identify YAP as a therapeutic target to augment GD2 immunotherapy responses in HR and relapsed NB.

Our team recently opened a first-in-child evaluation of unengineered allogeneic γδ T cells in combination with dinutuximab, an anti-GD2 antibody, and chemotherapy (NCT05400603)...Early studies demonstrate feasibility for innovative dual CAR expression and show promise for strong anti-NB potency. Future work will optimize CAR signaling domains for maximal efficacy in solid tumors, as well as confirm efficacy and safety in vivo with results rapidly translatable into our established γδ T cell clinical trial pipeline.

P2, N=42, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2023 --> Dec 2023

P1, N=45, Active, not recruiting, New Approaches to Neuroblastoma Therapy Consortium | Recruiting --> Active, not recruiting

These findings are consistent with those of prior studies showing that KIR/KIR-ligand genotypes are associated with clinical outcomes following anti-GD2 immunotherapy in children with neuroblastoma. The current study confirms the importance of KIR/KIR-ligand genotype in the context of I/T/DIN/GM-CSF chemoimmunotherapy administered to patients with relapsed or refractory disease in a clinical trial. These results are important because this regimen is now widely used for treatment of patients at time of first relapse/first declaration of refractory disease. Efforts to assess the role of NK cells and genes that influence their function in response to immunotherapy are ongoing.

P1, N=50, Recruiting, New Approaches to Neuroblastoma Therapy Consortium | Trial completion date: Mar 2023 --> Jun 2024 | Trial primary completion date: Sep 2022 --> Jun 2023

Approximately half of patients receiving I/T/DIN/GM-CSF for relapsed HRNB had objective responses. Patients with initial SD were unlikely to have an objective response, but > 1 of 3 patients with MR/PR on first evaluation ultimately had complete response. I/T/DIN/GM-CSF was associated with extended PFS in responders both during and after discontinuation of treatment. This study establishes a new comparator for response and survival in patients with relapsed HRNB.

Objective: GD2 is a tumor-associated ganglioside that is highly expressed in neuroblastoma and is targeted by two FDA-approved agents, dinutuximab and naxitamab. RNA expression of B4GALNT1 seemed to correlate and cluster better with known levels of GD2 expression than ST8SIA1 in neuroblastoma patients who historically have very high levels of GD2 expression via IHC. In sarcomas, MPNSTs had expression levels higher than that of even osteosarcoma which has been the center of clinical trials in sarcomas for GD2-targeted therapy. Given the response of bone disease with dinutuximab and naxitinib in pediatric patients with neuroblastoma, it suggests potential utility of treatment in sarcomas outside of neuroblastoma.

The combination of dinutuximab with GM-CSF did not significantly improve DCR in recurrent osteosarcoma. Dinutuximab toxicity and pharmacokinetics in adolescent and young adult osteosarcoma patients were similar to younger patients. Other strategies for targeting GD2 in osteosarcoma are being developed.