A safety/feasibility trial of the addition of the humanized anti-GD2 antibody (HU14.18K322A) with and without natural killer cells to chemotherapy in children and adolescents with recurrent/refractory neuroblastoma (SJGD2NK) and pretreatment anti-therapeutic antibodies (PATA) in patients treated with HU14.18K322A antibody
Why were these studies done?
SJGD2NK used an antibody called hu14.18K322A and natural killer (NK) cells in patients who have neuroblastoma that has come back or is hard to treat. This treatment was given along with chemotherapy (chemo).
Our immune system looks for and attacks cells that it sees as harmful, such as bacteria, viruses and cancer cells. Antibodies are part of the immune system. Hu14.18K322A is a monoclonal antibody, a protein made in a lab. We designed hu14.18K322A to bind to cancer cells that contain or “express” a molecule called an anti-GD2 antigen. Almost all neuroblastoma cells express this antigen. When hu14.18K322A binds to these types of cancer cells, it tells the immune system to attack and kill the cancer cells without harming nearby healthy cells.
NK cells are also special cells in our immune system that target cancer cells.
The study’s main goals were to:
- find out if this treatment is safe and kills tumor cells
- learn what kind of side effects occur
- study how the body uses the hu14.18K322A antibody
- find out whether the body makes antibodies against the hu14.18K322A
When were these studies done?
SJGD2NK took place between April 2012 and August 2014. PATA took place between July 2014 and April 2020.
What did the studies consist of?
- Immunotherapy with an antibody called hu14.18K322A
- Immunotherapy with NK cells from a donor (usually parent or other close relative).
- Three chemo regimens that are commonly used to treat neuroblastoma
What did we learn from these studies?
- Hu14.18K322A can be safely combined with three standard chemo regimens.
- In the past, patients had response rates of less than 50% with the chemo used in this study. Very few patients had a complete response (no evidence of tumor). But in this trial, the overall response rate was 61.5%. More than one-third of patients had a complete response or very good partial response.
- All patients in SJGD2NK benefited, and none had cancer that got worse during the study.
- The one-year survival rate was 77%.
- Because this was a pilot study that treated only a few patients, we could not tell whether the NK cells helped fight the cancer.
- In PATA, we found that 1 in 4 patients had preexisting antibodies in their blood to Hu14.18K322A. These patients had not already been treated with Hu14.18K322A. The preexisting antibodies did not neutralize the effects of the Hu14.18K3222A treatment. Interestingly we observed that such patients may respond better than others to monoclonal antibody therapy.
What are the next research steps as a result of this study?
This successful approach of using antibody and chemotherapy will be included in a different trial for patients with newly diagnosed high-risk neuroblastoma.
How does this study affect my child?
Every childhood cancer survivor should receive long-term follow-up care. Through the St. Jude After Completion of Care clinic, your child will receive information and guidance for care after treatment. Please speak with your St. Jude doctor about specific guidelines that apply to your child.
For more information
Please talk with your child’s St. Jude doctor about questions or concerns you have as a result of this study.
Publications generated from this study:
A Pilot Trial of Humanized Anti-GD2 Monoclonal Antibody (hu14.18K322A) with Chemotherapy and Natural Killer Cells in Children with Recurrent/Refractory Neuroblastoma. Federico SM, McCarville MB, Shulkin BL, Sondel PM, Hank JA, Hutson P, Meagher M, Shafer A, Ng CY, Leung W, Janssen WE, Wu J, Mao S, Brennan RC, Santana VM, Pappo AS, Furman WL. Clin Cancer Res. 2017 Nov 1;23(21):6441-6449.
Pre-existing Antitherapeutic Antibodies Against the Fc Region of the hu14.18K322A mAb are Associated with Outcome in Patients with Relapsed Neuroblastoma. Goldberg JL, Navid F, Hank JA, Erbe AK, Santana V, Gan J, de Bie F, Javaid AM, Hoefges A, Merdler M, Carmichael L, Kim K, Bishop MW, Meager MM, Gillies SD, Pandey JP, Sondel PM. J Immunother Cancer. 2020 Mar;8(1):e000590.