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Experimental antibody shows promise in Phase I trial for neuroblastoma
An experimental monoclonal antibody hu14.18K322A has shown encouraging results in a Phase I trial on children with advanced neuroblastoma. Of the 31 patients who received two or more rounds of treatment, tumours got smaller or disappeared altogether in 15 patients and progression of the disease was stopped temporarily. The antibody is targeted at the GD2 antigen, which is highly expressed on neuroblastoma tumour cells but with restricted expression on normal cells. The trial was carried out in St. Jude Children's Research Hospital. Results were recently published online ahead of print and will appear in the Journal of Clinical Oncology print edition on May 10th 2014.

Neuroblastoma affects the sympathetic nervous system. It is the most common cancer in children under the age of one year and accounts for 7-10% of all childhood cancers. The cure rate is high for some patients, especially infants. However, for other high-risk patients, for example those in whom the disease has spread, the prognosis is much poorer. Fewer than half of these achieve long-term, disease-free survival and new therapy development is a priority for these patients.
The Phase I trial was carried out in order to assess the maximum-tolerated dose and safety profile of hu14.18K322A, a modified antibody. The modification was intended to reduce activation of part of the immune response called the complement cascade and the pain associated with this activation. For the study, 38 patients were recruited whose cancer had returned or who had not responded to standard therapies such as surgery, chemotherapy, radiation and bone marrow transplants. These patients received different doses of hu14.18K322A. The antibody was administered every 28 days in daily doses over 4 days. The object of using this antibody is to mount an immune response specifically against the tumour cells, sparing the normal cells which have limited GD2 expression.

Of the 31 patients who went on to have two or more rounds of treatment, the disease was stabilised in nine of them. In two patients the tumours got smaller while they became undetectable in four more. First and corresponding author Dr Fariba Navid, added: "Four patients are alive after more than two-and-a-half years without additional therapy." Dr Navid further explained how the efficacy of the treatment was both encouraging and relatively unexpected at this early stage in the trial process: "This was the first time this experimental antibody was tried in patients. We were encouraged with the response…The percentage of patients who benefited from treatment with hu14.18K322A was unusual for a Phase I study."

Despite the reduction in complement activation, the most common side-effect of hu14.18K322A treatment was pain, with 68% of patients reporting severe pain in the first round of treatment. However, according to Dr Navid, the pain could be managed with medication, generally resolved within 24 hours of antibody administration and became less with additional rounds of treatment.
Hu14.18K322A is produced in the Children's GMP, LLC. Dr Navid acknowledged that the trial would have been impossible in the absence of GMP, an on-site facility that makes highly specialized pharmaceuticals under US government-approved Good Manufacturing Practices regulations. Clinical trials are on-going with the antibody, with the researchers now examining the impact of weekly dosing and looking at combining hu14.18K322A with other therapies.

Navid, F. et al. (2014) Phase I Trial of a Novel Anti-GD2 Monoclonal Antibody, Hu14.18K322A, Designed to Decrease Toxicity in Children With Refractory or Recurrent Neuroblastoma. Journal of Clinical Oncology, Published online before print April 7, 2014, doi: 10.1200/JCO.2013.50.4423

Press release: St. Jude Children's Research Hospital; available at
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Experimental antibody shows promise in Phase I trial for neuroblastoma00