Isolated limb perfusion with the tumor-targeting human monoclonal antibody-cytokine fusion protein L19-TNF plus melphalan and mild hyperthermia in patients with locally advanced extremity melanoma

Francesco Papadia, Valeria Basso, Roberto Patuzzo, Andrea Maurichi, Annabella Di Florio, Luciano Zardi, Elisa Ventura, Reinerio González-Iglesias, Valeria Lovato, Leonardo Giovannoni, Annaelisa Tasciotti, Dario Neri, Mario Santinami, Hans D. Menssen, Franco De Cian

Research output: Contribution to journalArticle

Abstract

Background: L19-TNF is a tumor-targeting immunocytokine composed of the human L19 antibody binding to extra domain B (ED-B) of fibronectin of newly formed blood vessels, and of human TNF. This exploratory trial evaluates safety and clinical activity of L19-TNF plus melphalan-containing isolated limb perfusion (ILP) in extremity melanoma patients. Methods: Seven and 10 patients received 325 μg and 650 μg of L19-TNF, respectively, during the ILP. Patients were studied for safety, tolerability, and clinical activity of this experimental L19-TNF ILP procedure. Results: Non-hematologic toxicity of L19-TNF ILP was very low, but severe myelosuppression was seen in four patients. Although L19-TNF was administered at a TNF-equivalent dose of only 3.13 and 6.25% of the approved TNF (Beromun®) dose of 4 mg, L19-TNF ILP induced objective responses in 86 and 89% of patients, respectively, including a complete response (CR) in 5/10 patients treated with L19-TNF ILP at 650 μg that was durable at 12 months in four patients. No CR was seen at 325 μg of L19-TNF. Conclusions: ILP with L19-TNF had a favorable safety and a promising activity profile at a dose of 650 μg of L19-TNF, supporting the exploration of higher L19-TNF doses and a Phase II trial comparing L19-TNF ILP with standard melphalan-containing ILP.

Original languageEnglish
Pages (from-to)173-179
Number of pages7
JournalJournal of Surgical Oncology
Volume107
Issue number2
DOIs
Publication statusPublished - Feb 2013

Keywords

  • extremity melanoma
  • targeted immunocytokine
  • vascular targeting
  • vasodisruptive therapy

ASJC Scopus subject areas

  • Surgery
  • Oncology

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