Ontuxizumab May Be Safe for Pediatric Patients With Relapsed/Refractory Solid Tumors
No dose-limiting toxicities were observed among the 6 patients who received ontuxizumab 4 mg/kg and 6 patients who received 8 mg/kg.
Ontuxizumab is well-tolerated among pediatric patients with relapsed or refractory solid tumors, according to a study published in Pediatric Blood & Cancer.1
Previous clinical trials demonstrated that ontuxizumab — a humanized IgG monoclonal antibody targeting endosialin, a glycoprotein found on the cell surface of mesenchymal cells and other tumors — inhibits tumor growth and is tolerated well among adult patients.
For this dose-finding phase 1 study (ClinicalTrials.gov Identifier: NCT01748721), researchers enrolled 27 pediatric patients and administered ontuxizumab at doses of 4, 8, or 12 mg/kg; the dose was escalated to 16 mg/kg if the maximum tolerated dose (MTD) was not reached and if pediatric systemic clearance was 30% or greater compared with adults. Upon determining the MTD/recommended phase 2 dose, 6 more patients were enrolled for a pharmacokinetic (PK) evaluation.
Of the 27 patients, 22 were fully evaluable for toxicity and 5 did not complete cycle 1 because of disease progression.
No dose-limiting toxicities (DLTs) were observed among the 6 patients who received 4 mg/kg and 6 patients who received 8 mg/kg.
Two of the 10 evaluable patients who received 12 mg/kg had DLTs of bacteremia and hyponatremia. Non-DLTs included grade 2 or less fever or infusion-related reactions, and were observed in 10 patients. Based on the toxicity profile, the phase 2 dose was determined to be 12 mg/kg.
The authors concluded that “while no objective responses were observed in this study, based on the mechanism of action, lack of myelosuppression, and tolerability, the evaluation of ontuxizumab in combination with chemotherapy or radiation with stratification based on serum PDGFRβ levels may be considered.”
- Norris RE, Fox E, Reid JM, et al. 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). Pediatr Blood Cancer. 2018 Jan 2. doi: 10.1002/pbc.26944 [Epub ahead of print]