Lexatumumab: Results of a phase I trial in pediatric patients with advanced solid tumors.

Abstract

9500 Background: Lexatumumab is an agonist, fully-human monoclonal antibody against TNF-Related Apoptosis Inducing Ligand Receptor 2 (TRAIL-R2) with preclinical evidence of activity in several pediatric solids tumors. A phase I trial in adult patients with solid tumors revealed a maximum tolerated dose of 10mg/kg IV every 14 days. Methods: This pediatric phase I, dose escalation study examined the safety, tolerability, pharmacokinetics, and immunogenicity of lexatumumab administered every 2 weeks to patients 21 years old and younger with recurrent or progressive solid tumors. Patient received increasing doses of lexatumumab (3, 5, 8, 10mg/m2) in a 3 + 3 design. Tumors were measured after 4 weeks, then every 2 months. Treatment was continued until disease progression or unacceptable toxicity. The expanded cohort at the maximum tolerated dose included 6 children (2-12yo) and 6 adolescents (13-21yo). Results: Twenty four patients received a total of 57 cycles of lexatumumab to date over 4 dose levels (3, 5, 8, and 10mg/kg q14days; 1 cycle = 28days). Stable disease occurred in 5 patients for 3 to 17 cycles. One patient had grade 2 pericarditis consistent with radiation recall, and one patient developed a grade 3 pneumonia with hypoxia during the second cycle of study drug. One patient with unresectable osteosarcoma pulmonary metastases continues on Lexatumumab 10mg/kg at 35+ doses (17+ cycles) with stable disease and marked clinical improvement. Transient clinical activity was observed in a patient with hepatoblastoma and Ewing sarcoma. Conclusions: Lexatumumab is well tolerated and can be safely administered every 14 days in pediatric patients. Pediatric patients tolerate 10 mg/kg, the maximum tolerated dose identified in adults. No significant financial relationships to disclose.