Phase II trial of the glycoprotein non-metastatic B-targeted antibody–drug conjugate, glembatumumab vedotin (CDX-011), in recurrent osteosarcoma AOST1521: A report from the Children's Oncology Group

Lisa M. Kopp, Suman Malempati, Mark Krailo, Yun Gao, Allen Buxton, Brenda J. Weigel, Thomas Hawthorne, Elizabeth Crowley, Jeffrey A. Moscow, Joel M. Reid, Victor Villalobos, R. Lor Randall, Richard Gorlick, Katherine A. Janeway

Research output: Contribution to journalArticle


Background: The prognosis is poor for children and adolescents with recurrent osteosarcoma (OS). Glycoprotein non-metastatic B (gpNMB) is a glycoprotein highly expressed in OS cells. We conducted a phase II study of glembatumumab vedotin (GV), a fully human IgG2 monoclonal antibody (CR011) against gpNMB conjugated to the microtubule inhibitor, monomethyl auristatin E. Patients and methods: Patients aged ≥12 years and <50 years with relapsed or refractory OS were eligible. GV 1.9 mg/kg/dose was administered on day 1 of each 21 day cycle. Pharmacokinetics were mandatory in patients aged <15 years. gpNMB expression was measured by immunohistochemistry. The primary end-point was disease control at 4 months and Response Evaluation Criteria in Solid Tumours response. A 2-stage design was used to determine efficacy. Results: Twenty-two patients were enrolled, and all were evaluable for response. Antibody–drug conjugate levels were detectable in patients, although small numbers limit comparison to adult data. The toxicities observed were similar to the previous studies with GV. The most common grade III adverse event was rash. One death from end organ failure occurred possibly related to GV. Of the 22 patients, one patient had a partial response, and two had stable disease. There was no correlation between gpNMB expression and response to GV. Conclusions: GV was well tolerated in this population. Although there was some antitumour activity, the extent of disease control in stage I did not meet the level required to proceed to stage II. Trial registration numbers: NCT02487979.

Original languageEnglish (US)
Pages (from-to)177-183
Number of pages7
JournalEuropean Journal of Cancer
Publication statusPublished - Nov 2019



  • Adolescent
  • Clinical trial
  • Molecular targeted therapy
  • Osteosarcoma
  • Paediatrics
  • Young adult

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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