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

Kopp LM, Malempati S, Krailo M, Gao Y, Buxton A, Weigel BJ, Hawthorne T, Crowley E, Moscow JA, Reid JM, Villalobos V, Randall RL, Gorlick R, Janeway KA. 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. Eur J Cancer. 2019 Nov;121:177-183. doi: 10.1016/j.ejca.2019.08.015. Epub 2019 Oct 3. PMID: 31586757; PMCID: PMC6952063.

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 (MMAE). Patients ≥ 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 (PK) were mandatory in patients < 15 years. gpNMB expression was measured by immunohistochemistry. The primary endpoint was disease control at 4 months and RECIST response. A 2-stage design was used to determine efficacy.