Dinutuximab beta for the treatment of Ewing sarcoma.

Abstract

e23503 Background: Ewing sarcoma is a rare and aggressive cancer with poor prognosis particularly for metastatic or recurrent cases. As GD2 is expressed on a high fraction of these tumors, we hypothesized that applying an anti-GD2 antibody may be a novel potential therapeutic modality. This study aims to investigate the efficacy of Dinutuximab beta in treating GD2-positive Ewing's sarcoma, both as a monotherapy and in combination with the standard chemotherapeutic agent doxorubicin. Methods: In vitro experiments were performed to evaluate both the binding affinity and cytotoxic efficacy of Dinutuximab beta in a GD2-positive human Ewing sarcoma-derived cell line. Additionally, in vivo studies were performed on a xenograft mouse model to evaluate the therapeutic efficacy of Dinutuximab beta alone and in combination with doxorubicin. The primary endpoints included tumor growth suppression and survival rate. Results: The findings demonstrate that Dinutuximab beta effectively suppressed tumor growth by 60% (p = 0.0135 vs vehicle) and improved survival rates by 68% (p = 0.0006 vs vehicle) in a mouse model (n = 8 mice per treatment group). The combination therapy with doxorubicin demonstrated superior efficacy compared to monotherapy, with enhanced tumor suppression (86%; p = 0.0009 vs vehicle) and an extension of survival rate (146%; p = 0.000025 vs vehicle). Conclusions: This pre-clinical study shows for the first time that dinutuximab beta in combination with standard of care improves survival. This lends support to continuing investigations of this novel therapeutic approach also in the clinical setting.