Background: Ontuxizumab is a humanized IgG mAb that targets the cell-surface glycoprotein endosialin (TEM-1/CD248). Endosialin is found in tumor stroma and vasculature across various tumors, with high expression in sarcoma and neuroblastoma but generally limited expression in normal tissue. Ontuxizumab binding to endosialin may interfere with platelet-derived growth factor (PDGF) signaling and prevention of protein interactions involved in tumor-stroma organization and new vessel formation. Methods: Ontuxizumab was administered intravenously on days (d) 1, 8, 15, and 22 of a 28 d cycle. Three dose levels (4, 8, and 12mg/kg) were evaluated using a rolling 6 design. Further dose escalation to 16mg/kg would proceed only if the ontuxizumab systemic clearance (CL) was ≥ 30% higher in children compared to adults and the maximum tolerated dose (MTD) was not reached. Primary endpoints were to describe toxicities, define MTD or recommended phase 2 dose (RP2D) and to characterize the pharmacokinetics (PK) of ontuxizumab in children. Following determination of MTD/RP2D an additional cohort of 6 pts < 12y was enrolled. PK was evaluated using non-compartmental and population PK modeling. Results: Twenty-seven eligible pts (17 male, median age 15y, range 3 – 21y) were enrolled. Twenty-two pts [neuroblastoma (5), Ewing sarcoma (4), rhabdomyosarcoma (4), other (9) tumors] were fully evaluable for toxicity. Five pts did not complete cycle 1 due to tumor progression. Grade ≥ 3 regimen-related non-hematologic toxicities included hypophosphatemia (1) and hyponatremia (1). One pt had grade 3 lymphopenia and 1 pt had grade 3 anemia in cycle 1. Grade ≤ 2 fever or infusion related reactions occurred in 9 pts. Dose-limiting bacteremia was observed during cycle 1 in 1 pt at dose level 3 (12mg/kg). Clearance was dose-dependent and within 30% of adult value (0.193 mL/h/kg) at 12mg/kg. Therefore there was no further dose escalation. Conclusions: The recommended dose of ontuxizumab in children is 12mg/kg administered weekly. This dose appears to be well tolerated in children with relapsed or refractory solid tumors. PK does not appear to be significantly different in children compared to adults. Clinical trial information: NCT01748721