Development of the ganglioside GD2 as a biomarker and clinical trial endpoint for childhood cancers

Tumor biomarkers (TB) that are validated surrogate endpoints of a drug’s therapeutic effect can improve the accuracy and sensitivity of assessing tumor response in phase 2 trials and could also substantially shorten the time line of phase 3 trials if they are predictive of subsequent relapse or survival. Our goal is to identify and validate TB to serve as surrogate endpoints in clinical trials to measure tumor burden and tumor response and to predict relapse. GD2 has many of the characteristics of an ideal biomarker. The overall objective of this proposal is to initiate the validation of GD2, which is expressed on the surface of neuroblastoma and other tumors of neuroectodermal or mesenchymal origin, as a TB for neuroblastoma using existing sample sets. Serum samples taken pre-treatment from 40 children with high-risk neuroblastoma from the ANBL00B1 repository were assayed for GD2 using the validated HPLC/MS/MS method in a LLQ of 10 ng/mL. GD2 was measurable in the serum of all patients with a mean ± S.D. concentration of 990 ± 823 ng/mL. GD2 was not quantifiable in pooled normal plasma. This request is for an exploratory set of serum samples taken at diagnosis from patients with high grade glioma or medulloblastoma to assess the specificity of GD2 as a TB for neuroblastoma and determine whether GD2 is present in the serum of children with CNS tumors