A Phase I, Open-Label, Dose Escalation Study of Enoblituzumab in Children and Young Adults with B7-H3-Expressing...

This multicenter, phase I, cohort expansion study was performed to characterize the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary antitumor activity of enoblituzumab in children with relapsed/refractory tumors expressing B7-H3 above a predetermined threshold.

Samples from 101 patients were screened for B7-H3 expression. Twenty-five patients with relapsed/refractory B7-H3-expressing solid tumors were enrolled in the trial with a median age of 14.8 years (range, 6-24 years). Enoblituzumab was administered intravenously weekly at 10 or 15 mg/kg.

B7-H3 expression was documented in 96% of evaluable tumors by IHC. The maximum administered dose of enoblituzumab was the protocol-specified maximum dose of 15 mg/kg as no dose-limiting toxicities were observed. Patients received a median of 6.5 doses (range 1-24), and the main toxicities encountered were infusion-related reactions. Pharmacokinetic studies showed that drug plasma concentrations fit a linear two-compartment model with a mean elimination half-life of 67 days. No objective tumor responses were documented.

B7-H3 is expressed on a high fraction of pediatric solid tumors spanning many different disease histologies. Enoblituzumab was well tolerated at a weekly dose of 15 mg/kg and induced inflammatory reactions in some patients though no objective responses were observed. Further testing of enoblituzumab in combination with other agents, or the use of other B7-H3-directed therapeutics, should be considered for children with relapsed solid tumors.

This phase I clinical trial is the first study to evaluate the feasibility and safety of administering enoblituzumab to pediatric patients with relapsed solid tumors. We demonstrated that B7-H3 is highly expressed across a wide variety of tumor histologies. Enoblituzumab could be safely administered at a dose of 15 mg/kg. However, no objective responses were observed, suggesting that alternative strategies to target B7-H3 for children with relapsed tumors should be considered.