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

PURPOSE

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.

PATIENTS AND METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

SIGNIFICANCE

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.