Phase 2 study of anti-disialoganglioside antibody, dinutuximab, in combination with GM-CSF in patients with recurrent osteosarcoma: A report from the Children’s Oncology Group

Hingorani P, Krailo M, Buxton A, Hutson P, Sondel PM, Diccianni M, Yu A, Morris CD, Womer RB, Crompton B, Randall RL, Teot LA, DuBois SG, Janeway KA, Gorlick RG, Isakoff MS. Phase 2 study of anti-disialoganglioside antibody, dinutuximab, in combination with GM-CSF in patients with recurrent osteosarcoma: A report from the Children’s Oncology Group. Eur J Cancer. 2022 Sep;172:264-275. doi: 10.1016/j.ejca.2022.05.035. Epub 2022 Jul 6. PubMed PMID: 35809374; PubMed Central PMCID: PMC9631806.

Novel effective therapies are urgently needed in recurrent osteosarcoma. GD2 is expressed in human osteosarcoma tumors and cell lines. This study evaluated the disease control rate (DCR) in patients with recurrent osteosarcoma treated with the anti-GD2 antibody dinutuximab plus cytokine therapy as compared to historical outcomes. AOST1421 was a single-arm phase 2 study for patients with recurrent pulmonary osteosarcoma in complete surgical remission. Patients received up to five cycles of dinutuximab (70mg/m2/cycle) with GM-CSF. Two different dinutuximab infusion schedules were studied: 35mg/m2/day over 20 hours (2-day) and 17.5mg/m2/day over 10 hours (4-day). Primary end point was DCR, defined as proportion of patients event-free at 12 months from enrollment. The historical benchmark was 12-month DCR of 20% (95% CI 10–34%). Dinutuximab would be considered effective if ≥16/39 patients remained event-free. Secondary objectives included toxicity evaluation and pharmacokinetics (PK).