Phase I trial and pharmacokinetic study of lexatumumab in pediatric patients with solid tumors.
OBJECTIVE
Lexatumumab is an agonistic, fully human monoclonal antibody against tumor necrosis factor-related apoptosis-inducing ligand receptor 2 with preclinical evidence of activity in pediatric solid tumors.


METHODS
This phase I dose-escalation study examined the safety, tolerability, pharmacokinetics, and immunogenicity of lexatumumab at doses up to, but not exceeding, the adult maximum-tolerated dose (3, 5, 8, and 10 mg/kg), administered once every 2 weeks to patients age≤21 years with recurrent or progressive solid tumors.


RESULTS
Twenty-four patients received a total of 56 cycles of lexatumumab over all four planned dose levels. One patient had grade 2 pericarditis consistent with radiation recall, and one patient developed grade 3 pneumonia with hypoxia during the second cycle. Five patients experienced stable disease for three to 24 cycles. No patients experienced complete or partial response, but several showed evidence of antitumor activity, including one patient with recurrent progressive osteosarcoma who experienced resolution of clinical symptoms and positron emission tomography activity, ongoing more than 1 year off therapy. One patient with hepatoblastoma showed a dramatic biomarker response.


CONCLUSIONS
Pediatric patients tolerate 10 mg/kg of lexatumumab administered once every 14 days, the maximum-tolerated dose identified in adults. The drug seems to mediate some clinical activity in pediatric solid tumors and may work with radiation to enhance antitumor effects.
National Cancer Institute, National Institutes of Health, 10 Center Dr, Building 10 CRC, Room 1W-3750, Bethesda, MD 20892-1104, USA. merchanm@mail.nih.gov
Melinda S
MS
Merchant
James I
JI
Geller
Kristin
K
Baird
Alexander J
AJ
Chou
Susana
S
Galli
Ava
A
Charles
Martha
M
Amaoko
Eunice H
EH
Rhee
Anita
A
Price
Leonard H
LH
Wexler
Paul A
PA
Meyers
Brigitte C
BC
Widemann
Maria
M
Tsokos
Crystal L
CL
Mackall
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016896:Treatment Outcome; D055815:Young Adult
D000911:Antibodies, Monoclonal; C510234:lexatumumab