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.

Abstract

PURPOSE:

Novel effective therapies are urgently needed in recurrent osteosarcoma. GD2 is expressed in human osteosarcoma tumours 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.

METHODS:

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 (70 mg/m2/cycle) with granulocyte-macrophage colony-stimulating factor (GM-CSF). Two different dinutuximab infusion schedules were studied: 35 mg/m2/day over 20 h (2 days) and 17.5 mg/m2/day over 10 h (4 days). Primary end point was DCR, defined as a proportion of patients event free at 12 months from enrolment. 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.

RESULTS:

Thirty-nine eligible patients were included in the outcome analysis. Dinutuximab did not demonstrate evidence of efficacy as 11/39 patients remained event free for a DCR of 28.2% (95% CI 15-44.9%). One of 136 administered therapy cycles met criteria for unacceptable toxicity when a patient experienced sudden death of unknown cause. Other ≥ Grade 3 toxicities included pain, diarrhoea, hypoxia, and hypotension. Pharmacokinetic parameters were similar in the two schedules.

CONCLUSIONS:

The combination of dinutuximab with GM-CSF did not significantly improve DCR in recurrent osteosarcoma. Dinutuximab toxicity and pharmacokinetics in adolescent and young adult osteosarcoma patients were similar to younger patients. Other strategies for targeting GD2 in osteosarcoma are being developed.

• Authors: Pooja Hingorani, Mark Krailo, Allen Buxton, Paul Hutson, Paul M Sondel, Mitchell Diccianni, Alice Yu, Carol D Morris, Richard B Womer, Brian Crompton, R Lor Randall, Lisa A Teot, Steven G DuBois, Katherine A Janeway, Richard G Gorlick, Michael S Isakoff
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 172 Pg. 264-275 (Sep 2022) ISSN: 1879-0852 [Electronic] England
• PMID: 35809374 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2022 Elsevier Ltd. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• dinutuximab
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Adolescent
• Antibodies, Monoclonal
• Antineoplastic Combined Chemotherapy Protocols (toxicity)
• Bone Neoplasms (drug therapy)
• Child
• Granulocyte-Macrophage Colony-Stimulating Factor (therapeutic use)
• Humans
• Neoplasm Recurrence, Local (drug therapy)
• Osteosarcoma (drug therapy)
• Young Adult