A phase III, multicenter, open-label study of dinutuximab beta without/with chemotherapy at the investigator’s choice in patients under 18 years old with bone and soft tissue sarcomas with positive expression GD2 and disease progression during the first-line chemotherapy

Introduction . Tumor-associated gangliosides are overexpressed on a large number of tumors. The ratio of the amount of gangliosides varies from one type of tumor to another. Tissue restriction of GD2 expression in normal cells and its presence in a wide range of human tumor diseases has increased the relevance of GD2 as a target for immunooncology drugs. The aim of the study was to improve the efficacy of the treatment of children and adolescents with refractory and recurrent solid malignancies (soft tissue, undifferentiated and bone sarcomas) by incorporating targeted immunotherapeutic options (passive immunotherapy with antiGD2 monoclonal antibodies (MA)) into comprehensive therapy programs. The primary objective of the study was to analyze the efficacy of tandem use of antiGD2 MA and 2+ line chemotherapy on survival. Secondary targets were overall response rate (complete remission (CR) + partial remission (PR)), tumor control rate (CR + PR + stabilization), duration of response, and immune-associated adverse events. Materials and methods . The clinical study protocol was initiated at the Petrov National Medical Research Center of Oncology of the Ministry of Health of Russia and approved by the local ethics committee No. 8 of 21.05.2021. On the basis of a signed memorandum of cooperation, the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov at N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia. The study is prospective. It is planned to evaluate the efficacy and safety of using antiGD2 MA and 2+ line chemotherapy at the investigator's choice in patients under 18 years of age with bone, soft tissue and undifferentiated sarcomas with positive GD2 expression and disease progression/recurrence on/after the 1st line of polychemotherapy. This study screened 40 patients to randomize 10 patients. In the future, an additional set of patients is planned. Conclusion. Based on the results obtained, the efficacy and safety of using a combination of antiGD2 immunotherapy and 2+ line chemotherapy in patients under 18 years of age with refractory and recurrent forms of bone and soft-tissue GD2-positive sarcomas will be concluded.