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 language||English (US)|
|Number of pages||7|
|Journal||European Journal of Cancer|
|State||Published - Nov 2019|
Bibliographical noteFunding Information:
The authors are grateful to all the adolescents and young adults and their families that they have the privilege of caring for who participated in this study. Also, they are very thankful to the study teams at the participating centres as well as NIH/CTEP, Celldex and Mosaic Laboratories. This work was supported by the National Clinical Trials Network Operations Center Grant, the National Clinical Trials Network Statistics and Data Center Grant and the St. Baldrick's Foundation.
L.M.K. is an employee of the contract research organisation Covance. M.K. is a consultant for Merck. K.A.J. has received travel reimbursement from Loxo oncology. R.G. has received laboratory research funding from Eisai. T.H. and E.C. are employees of Celldex.
This work was supported by the National Clinical Trials Network Operations Center Grant, the National Clinical Trials Network Statistics and Data Center Grant and the St. Baldrick's Foundation .
© 2019 Elsevier Ltd
- Clinical trial
- Molecular targeted therapy
- Young adult
PubMed: MeSH publication types
- Journal Article