Phase I trial and pharmacokinetic study of lexatumumab in pediatric patients with solid tumors

Melinda S. Merchant, James I. Geller, Kristin Baird, Alexander Ja-Ho Chou, Susana Galli, Ava Charles, Martha Amaoko, Eunice H. Rhee, Anita Price, Leonard H. Wexler, Paul A. Meyers, Brigitte C. Widemann, Maria Tsokos, Crystal L. Mackall

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Purpose: 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. Patients and 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)4141-4147
Number of pages7
JournalJournal of Clinical Oncology
Volume30
Issue number33
DOIs
StatePublished - Nov 20 2012
Externally publishedYes

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Pharmacokinetics
Pediatrics
Neoplasms
Maximum Tolerated Dose
lexatumumab
Radiation
Hepatoblastoma
Pericarditis
Osteosarcoma
Positron-Emission Tomography
Pneumonia
Tumor Necrosis Factor-alpha
Biomarkers
Monoclonal Antibodies
Apoptosis
Ligands
Safety
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Phase I trial and pharmacokinetic study of lexatumumab in pediatric patients with solid tumors. / Merchant, Melinda S.; Geller, James I.; Baird, Kristin; Chou, Alexander Ja-Ho; Galli, Susana; Charles, Ava; Amaoko, Martha; Rhee, Eunice H.; Price, Anita; Wexler, Leonard H.; Meyers, Paul A.; Widemann, Brigitte C.; Tsokos, Maria; Mackall, Crystal L.

In: Journal of Clinical Oncology, Vol. 30, No. 33, 20.11.2012, p. 4141-4147.

Research output: Contribution to journalArticle

Merchant, MS, Geller, JI, Baird, K, Chou, AJ-H, Galli, S, Charles, A, Amaoko, M, Rhee, EH, Price, A, Wexler, LH, Meyers, PA, Widemann, BC, Tsokos, M & Mackall, CL 2012, 'Phase I trial and pharmacokinetic study of lexatumumab in pediatric patients with solid tumors', Journal of Clinical Oncology, vol. 30, no. 33, pp. 4141-4147. https://doi.org/10.1200/JCO.2012.44.1055
Merchant, Melinda S. ; Geller, James I. ; Baird, Kristin ; Chou, Alexander Ja-Ho ; Galli, Susana ; Charles, Ava ; Amaoko, Martha ; Rhee, Eunice H. ; Price, Anita ; Wexler, Leonard H. ; Meyers, Paul A. ; Widemann, Brigitte C. ; Tsokos, Maria ; Mackall, Crystal L. / Phase I trial and pharmacokinetic study of lexatumumab in pediatric patients with solid tumors. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 33. pp. 4141-4147.
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