Danyelza (naxitamab-gqgk)

P2, N=122, Recruiting, Y-mAbs Therapeutics | Trial primary completion date: May 2025 --> Apr 2026

P=N/A, N=64, Recruiting, Guangzhou Women and Children's Medical Center

P2, N=45, Recruiting, Memorial Sloan Kettering Cancer Center

P1, N=48, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Phase classification: P2 --> P1 | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

P2, N=59, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

P2, N=46, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting

P1, N=85, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025

P2, N=24, Recruiting, Anna Raciborska | Not yet recruiting --> Recruiting

Unexpectedly, her brain metastasis responded clinically, histologically, and by imaging to the treatment. We believe this is the first documented case of NBL of the brain responding to NAX.

P1/2, N=186, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025

This comprehensive review summarizes clinical data regarding efficacy and safety of GM-CSF, recombinant human granulocyte colony-stimulating factor (G-CSF) or no cytokine in combination with anti-GD2 monoclonal antibodies (ie, dinutuximab, dinutuximab beta or naxitamab) for immunotherapy of patients with high-risk neuroblastoma...Suboptimal efficacy outcomes with G-CSF raise concerns about its suitability as an alternative to GM-CSF as an adjuvant in immunotherapy for patients with high-risk neuroblastoma. While programs exist to facilitate obtaining GM-CSF and anti-GD2 monoclonal antibodies in regions where they are not commercially available, continued work is needed to ensure equitable therapeutic options are available globally.

P1/2, N=42, Recruiting, Margaret Gatti-Mays | Phase classification: P1b/2 --> P1/2

P1/2, N=42, Recruiting, Margaret Gatti-Mays

P=N/A, N=7, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2023 --> Nov 2024 | Trial primary completion date: Nov 2023 --> Nov 2024

P1b/2, N=42, Recruiting, Margaret Gatti-Mays | Not yet recruiting --> Recruiting

We investigated the combination of humanized anti-GD2 mAb naxitamab (Hu3F8), irinotecan (I), temozolomide (T), and sargramostim (GM-CSF)-HITS-against primary resistant HR-NB. Cohort 1 had a 3-year OS of 84.8% and EFS 54.4%, which are statistically significant improvements (EFS p = 0.0041 and OS p = 0.0037) compared to cohort 2. In conclusion, naxitamab-based chemo-immunotherapy is effective against primary chemo-resistant HR-NB, increasing long-term outcomes when administered early during the course of treatment.

P4, N=62, Not yet recruiting, SciClone Pharmaceuticals

P2, N=48, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2023 --> Jun 2024 | Trial primary completion date: Jun 2023 --> Jun 2024

P1, N=68, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed

P2, N=59, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2023 --> Jun 2024 | Trial primary completion date: Jun 2023 --> Jun 2024

Mean serum naxitamab levels pre- and post-STU (11.46 µg/ml pre-infusion; 100.95 µg/ml post-infusion) were within the range reported for SIR. The comparable pharmacokinetics of naxitamab during SIR and STU may indicate that switching to STU reduces G3 AEs without impact on efficacy.

Cox models showed only MRD as a predictor of EFS. In conclusion, consolidation with naxitamab resulted in reassuring survival rates for HR-NB patients after end-induction CR.

Patients did not receive isotretinoin. This large experience confirms that the new schedule is safe and, despite short follow-up, appears as effective as the prior schedule.

At time of approval, the safety of naxitamab per the USPI was evaluated across 97 patients from two open-label, single arm studies (Trials 201 and 12-230). Two years after approval, with more patients receiving naxitamab in the real-world clinical setting, SAERs indicate the safety profile for naxitamab remains consistent with adverse reactions reported in the clinical trials.

Evaluation of patients with R/R HR-NB in bone treated with naxitamab+GM-CSF showed a similar ORR regardless of baseline CS (≤2 or ≥3). In patients with evaluable bone disease, naxitamab provided clinically meaningful response rates in the bone compartment and reduction in CS with an acceptable safety profile. Naxitamab+GM-CSF is an attractive therapeutic option for patients with R/R HR-NB in bone.  This study was funded by Y-mAbs Therapeutics, Inc.

Case 3 achieved CR after chemotherapy, surgery, metaiodobenzylguanidine, and 3F-8 (Naxitamab) immunotherapy after the initial diagnosis...ARID1B is a component protein of the SWI/SNF chromatin-remodeling complex that participates in the occurrence of a variety of tumors by regulating DNA repair and synthesis. ARID1B nucleic acid mutation (p.A460, p.V215G) in the promoter region of three children may contribute to the poor prognosis of NB children.

P=N/A, N=7, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2022 --> Nov 2023 | Trial primary completion date: Nov 2022 --> Nov 2023

P2, N=76, Recruiting, Wake Forest University Health Sciences | Not yet recruiting --> Recruiting

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.

P2, N=0, Withdrawn, Y-mAbs Therapeutics | N=120 --> 0 | Recruiting --> Withdrawn

P1, N=68, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Aug 2022 --> Aug 2023 | Trial primary completion date: Aug 2022 --> Aug 2023

P2, N=76, Not yet recruiting, Wake Forest University Health Sciences

P2, N=59, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2022 --> Jun 2023 | Trial primary completion date: Jun 2022 --> Jun 2023

The team at Sant Joan de Déu Children's Hospital in Barcelona, Spain, have been using naxitamab to treat neuroblastoma under clinical trial protocols [e.g. Trial 201, and hu3F8, irinotecan, temozolomide, and sargramostim (GM-CSF) (HITS) study] and compassionate use since 2017. Adverse event management, including the use of ketamine to manage pain during anti-GD2 mAb infusions, is also discussed. We hope this will provide practical information for other health care providers considering offering this treatment.

Key exclusion criteria include prior treatment with duration ≤3 wks (chemotherapy), ≤6wks (autologous stem cell transplant or therapeutic 131I-MIBG), ≤4wks (radiation therapy), or progressed while on anti-GD2; residual NB in the bone marrow only; and CNS/leptomeningeal disease in the prior 6 mo. Response rates will be assessed using the 2-sided binomial test at the 5% significance level; DoR, PFS, and OS will be estimated using Kaplan-Meier analysis. Adverse events will be graded per CTCAE.

P1, N=85, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2022 --> Jan 2024 | Trial primary completion date: Jan 2022 --> Jan 2024

P2, N=120, Recruiting, Y-mAbs Therapeutics | Not yet recruiting --> Recruiting

Initial outcomes with naxitamab are encouraging; however, future trials to maximize drug tolerance and elucidate its optimal role in neuroblastoma therapy in conjunction with other treatment strategies are needed. This review discusses the use of naxitamab in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment of r/r HR NBL.

P=N/A, N=7, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2021 --> Nov 2022 | Trial primary completion date: Nov 2021 --> Nov 2022