Phase I/II study of the tumour-targeting human monoclonal antibody–cytokine fusion protein L19-TNF in patients with advanced solid tumours

  • G. Spitaleri
  • R. Berardi
  • C. Pierantoni
  • T. De Pas
  • C. Noberasco
  • C. Libbra
  • R. González-Iglesias
  • L. Giovannoni
  • A. Tasciotti
  • D. Neri
  • H. D. Menssen
  • F. de Braud
Original Paper

Abstract

Purpose

L19-TNF is an armed antibody that selectively targets human TNF to extra domain B-fibronectin on tumour blood vessels. We performed a phase I/II first-in-man trial with L19-TNF monotherapy in metastatic solid cancer patients to study safety and signs of clinical activity.

Methods

Six cohorts of patients were treated with increasing (1.3–13 μg/kg) doses of intravenous L19-TNF on day 1, 3, and 5 of repeated 3-weekly cycles, and 12 colorectal cancer patients were treated at 13 μg/kg. PK, antibody formation, changes in lymphocyte subsets, 5-HIAA plasma levels as well as safety and clinical activity were analysed.

Results

Thirty-four patients received at least one L19-TNF dose. The serum half-life of L19-TNF at 13 μg/kg was 33.6 min, and maximum peak serum concentration was 73.14 μg/L. Mild chills, nausea and vomiting but no haemato- or unexpected toxicity were observed. Grade 3 lumbar pain in bone metastasis was the only dose-limiting toxicity found in one patient. Objective tumour responses were not detected. Transient stable disease occurred in 19 of 31 evaluable patients.

Conclusions

Intravenous L19-TNF on day 1, 3, and 5 of a 3-weekly schedule was safe up to 13 μg/kg, but did not result in objective tumour responses. The maximally tolerated dose (MTD) was not reached, allowing for further dose escalation of L19-TNF possibly in combination with chemotherapy.

Keywords

Armed antibody Immunocytokine L19-TNF Phase I/II trial Vascular targeting Vasodisruptive therapy 

Supplementary material

432_2012_1327_MOESM1_ESM.docx (90 kb)
Supplementary material 1 (DOCX 90 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • G. Spitaleri
    • 1
  • R. Berardi
    • 2
  • C. Pierantoni
    • 2
  • T. De Pas
    • 1
  • C. Noberasco
    • 1
  • C. Libbra
    • 3
  • R. González-Iglesias
    • 3
  • L. Giovannoni
    • 3
  • A. Tasciotti
    • 3
  • D. Neri
    • 4
  • H. D. Menssen
    • 3
  • F. de Braud
    • 1
    • 5
  1. 1.Istituto Europeo di OncologiaMilanItaly
  2. 2.Clinica di Oncologia MedicaAzienda Ospedaliero Universitaria Ospedali Riuniti Umberto IAnconaItaly
  3. 3.Philogen S.p.A.SienaItaly
  4. 4.Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical SciencesETH ZurichZurichSwitzerland
  5. 5.Fondazione IRCCS Istituto Nazionale TumoriMilanItaly

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