The strategic objective of the BUTTERFLY study is to estimate the safety and initial efficacy of advanced therapy (personalized chemoimmunotherapy) with a new antibody targeting all children and young adults with refractory GD2-expressing Ewing’s sarcoma in Poland. Also, if the outcomes improve in patients with GD2 expression, the above diagnostics will be used in risk stratification as a potential determinant for the choice of personalized therapy. The study is in line with the strategy to improve the quality and efficacy of treating patients with refractory/relapsed Ewing's sarcoma in Poland. The innovative nature of BUTTERFLY study (the first immunotherapy in bone tumours and the first anti-GD2 therapy in Ewing’s sarcoma in Poland) also aims to harmonize and standardize diagnostics and therapy in patients with refractory and relapsed disease (examination, personalized treatment) and will boost further development of personalized therapy through a biobank allowing access to biological material in this rare disease. The study is to cover the entire population of children, adolescents and young adults aged 2 to 21 with refractory/relapsed Ewing's sarcoma.
Ewing's sarcoma (ES) is a highly aggressive form of cancer. The incidence rate increases with age (median age 15-19 years). Unfortunately, 20-30% of patients experience therapy failure. The five-year overall survival rate is 20-25% in relapse, and the two-year survival rate is achieved by less than 5% of patients refractory to first-line therapy.
For more than 30 years, no improvement has been achieved in the outcomes despite increasing doses of chemotherapy and radiation, invasive surgical procedures in patients with disseminated disease and poor prognostic markers. Consequently, other treatment options are being explored.
Gangliosides are membrane-bound glycosphingolipids. They have roles in various functions of stem cells, including signal transduction, stem cell proliferation and differentiation, intercellular adhesion and cell death mechanisms. Changes in the expression of gangliosides have been observed in tumour cells. GD2 ganglioside is expressed intensively in neuroblastoma (NBL), osteosarcoma and other malignancies such as Ewing's sarcoma. According to early findings, GD2 has been found on the surface of tumour cells in 60-80% of patients with ES. Activity of Naxitamab was recorded in NBL patients with GD2-expressing tumour cells. The clinical efficacy of anti-GD2 therapy in NBL, as well as preclinical evidence of GD2-specific T cell therapy activity against ES xenografts, justify clinical trial of Naxitamab in combination with chemotherapy for Ewing sarcoma.
The chemotherapy protocol of the B Study will be based on NBL treatment data, administration of Irinotecan and Temozolomide (IT) and a standard and well-tolerated therapy for refractory/relapsed ES. Data from NBL trials support the safety of combining IT with anti-GD2 therapy, even in patients previously receiving aggressive treatment.
The addition of Naxitamab to chemotherapy regimen in the treatment of patients with refractory/relapsed Ewing’s sarcoma can improve the outcomes. Based on the findings presented above, the clinical research project aims to evaluate the safety of combining Naxitamab with a standard 3-weekly chemotherapy (CHT) in patients with refractory/relapsed Ewing's sarcoma.