Phase I Study Finds Novel Antibody Shows Promise in Children With Advanced Neuroblastoma


Key Points

  • In a phase I study of hu14.18K322A in 38 children with refractory or recurrent neuroblastoma, tumors shrank or disappeared and disease progression was halted in 15 patients.
  • Four patients are still alive after more than 2.5 years without additional treatment.
  • Hu14.18K322A may also prove effective in other cancers characterized by GD2 expression, including melanoma, small cell lung cancer, and sarcomas, and should be tested in these diseases.

Researchers from St. Jude Children’s Research Hospital conducted a phase I study of hu14.18K322A, an experimental monoclonal antibody genetically engineered at the hospital, in 38 children with refractory or recurrent neuroblastoma. The patients received escalating doses of hu14.18K322A ranging from 2 to 70 mg/m2 per day for 4 consecutive days every 28 days.

Of the 31 patients evaluated after two or more courses of treatment, the disease stabilized in nine patients and tumors shrank in two patients and were undetectable in four more patients. Four patients are still alive after more than 2.5 years without additional therapy. The study by Navid was published in the May 10 issue of the Journal of Clinical Oncology.

Experimental Antibody

Hu14.18K322A is a humanized anti-GD2 monoclonal antibody with a single point mutation (K322A) that reduces complement-dependent lysis. The GD2 antigen is found on the surface of nearly all neuroblastoma cells as well as other cancer types, including melanoma, osteosarcoma, and soft-tissue sarcomas. Because the antibody has fewer mouse components, theoretically making it less immunogenic, it is less likely the body will reject the antibody, according to the researchers.

“This was the first time this experimental antibody was tried in patients. We were encouraged with the response,” Fariba Navid, MD, lead author of the study and an Associate Member in the Department of Oncology at St. Jude Children’s Research Hospital, said in a statement. “The percentage of patients who benefited from treatment with hu14.18K322A was unusual for a phase I study.”

The positive results from the phase I study have prompted the researchers to expand clinical trials of hu14.18K322A to include newly diagnosed neuroblastoma patients. The researchers are also testing the impact of giving the monoclonal antibody weekly rather than every 28 days and in combination with other therapies.

Side Effects

Dose-limiting grade 3 or 4 toxicities occurred in 4 of 36 evaluable patients and were characterized by cough, asthenia, sensory neuropathy, anorexia, serum sickness, and hypertensive encephalopathy. The most common non–dose-limiting grade 3 or 4 toxicities during course 1 were pain (68%) and fever (21%). Pain was worse on day 1 of course 1, and improved with each subsequent course; in nearly all cases, pain resolved 24 hours after the last infusion on day 4.

Potential Therapy for Other Cancers

The researchers noted that while the clinical benefit of anti-GD2 monoclonal antibodies has been seen in neuroblastoma, spurring ongoing testing of anti-GD2 in that rare cancer, other more common malignancies also characterized by GD2 expression—such as melanoma, small cell lung cancer, and sarcomas—may achieve a clinical benefit from the antibody as well. “Novel strategies using hu14.18K322A may be developed and tested in these diseases,” concluded the researchers.

This study was funded by grants from the National Institutes of Health, the St. Baldrick’s Foundation, the Crawdaddy Foundation, the Evan Dunbar Foundation, and ALSAC.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.