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Clinical Trial
. 2022 Sep:172:264-275.
doi: 10.1016/j.ejca.2022.05.035. Epub 2022 Jul 6.

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

Pooja Hingorani  1 , Mark Krailo  2 , Allen Buxton  3 , Paul Hutson  4 , Paul M Sondel  5 , Mitchell Diccianni  6 , Alice Yu  6 , Carol D Morris  7 , Richard B Womer  8 , Brian Crompton  9 , R Lor Randall  10 , Lisa A Teot  9 , Steven G DuBois  9 , Katherine A Janeway  9 , Richard G Gorlick  11 , Michael S Isakoff  12
Affiliations
Clinical Trial

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

Pooja Hingorani et al. Eur J Cancer. 2022 Sep.

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.

Keywords: Dinutuximab; GD2; Recurrent osteosarcoma.

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Conflict of interest statement

Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SGD has received consulting fees from Amgen, Bayer, and Jazz as well as travel expenses from Loxo, Roche, and Salarius. MDK has received consulting fees from Merck, Sharpe and Dhome. KAJ has received consulting fees from Bayer and Ipsen and honoraria from Takeda and Foundation Medicine. The remaining authors have no conflicts of interest.

Figures

Figure 1a:
Figure 1a:
Study design schema for AOST1421
Figure 1b:
Figure 1b:
CONSORT diagram showing patient allocation and disposition
Figure 2:
Figure 2:
Kaplan-Meier estimates of event-free and overall survival in 39 patients with relapsed osteosarcoma treated with dinutuximab after complete surgical resection of recurrent disease.
See this image and copyright information in PMC

References

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