Phase 1 trial of ontuxizumab (MORAb‐004) in children with relapsed or refractory solid tumors: A report from the Children's Oncology Group Phase 1 Pilot Consortium (ADVL1213)

• Published in: Pediatric blood & cancer 2018-05, Vol.65 (5), p.e26944-n/a
• Main Authors: Norris, Robin E., Fox, Elizabeth, Reid, Joel M., Ralya, Andrew, Liu, Xiaowei W., Minard, Charles, Weigel, Brenda J.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Antibodies, Monoclonal, Humanized - therapeutic use; Bacteremia; Cell surface; Child; Child, Preschool; Children; Cohort Studies; Drug Resistance, Neoplasm - drug effects; Ewing's sarcoma; Female; Fever; Follow-Up Studies; Hematology; Humans; Hyponatremia; Immunoglobulin G; Infant; Male; Maximum Tolerated Dose; Mesenchyme; Monoclonal antibodies; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - pathology; Neoplasms - drug therapy; Neoplasms - pathology; Neuroblastoma; Oncology; ontuxizumab; Pediatrics; Pharmacokinetics; phase 1; Prognosis; Rhabdomyosarcoma; Salvage Therapy; Sarcoma; Solid tumors; Stroma; Survival Rate; Toxicity; Tumors; Young Adult
• ISSN: 1545-5009; 1545-5017
• DOI: 10.1002/pbc.26944

Background Ontuxizumab is a humanized IgG monoclonal antibody that targets the cell‐surface glycoprotein endosialin (tumor endothelial marker‐1[TEM‐1]/CD248) found on activated mesenchymal cells and certain tumors. Ontuxizumab binding to endosialin may interfere with platelet‐derived growth factor signaling, prevent tumor stroma organization, and prevent new vessel formation. Methods Ontuxizumab was administered intravenously on days 1, 8, 15, and 22 of a 28‐day cycle at three dose levels (4, 8, and 12 mg/kg). Further dose escalation to 16 mg/kg was planned if the maximum tolerated dose (MTD) was not reached and the ontuxizumab systemic clearance was ≥30% higher in children compared to adults. Following determination of the MTD/recommended phase 2 dose, an additional cohort of six patients (