Journal of Cancer Research and Clinical Oncology

, Volume 139, Issue 3, pp 447–455

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


  • G. Spitaleri
    • Istituto Europeo di Oncologia
  • R. Berardi
    • Clinica di Oncologia MedicaAzienda Ospedaliero Universitaria Ospedali Riuniti Umberto I
  • C. Pierantoni
    • Clinica di Oncologia MedicaAzienda Ospedaliero Universitaria Ospedali Riuniti Umberto I
  • T. De Pas
    • Istituto Europeo di Oncologia
  • C. Noberasco
    • Istituto Europeo di Oncologia
  • C. Libbra
    • Philogen S.p.A.
  • R. González-Iglesias
    • Philogen S.p.A.
  • L. Giovannoni
    • Philogen S.p.A.
  • A. Tasciotti
    • Philogen S.p.A.
  • D. Neri
    • Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical SciencesETH Zurich
  • H. D. Menssen
    • Philogen S.p.A.
    • Istituto Europeo di Oncologia
    • Fondazione IRCCS Istituto Nazionale Tumori
Original Paper

DOI: 10.1007/s00432-012-1327-7

Cite this article as:
Spitaleri, G., Berardi, R., Pierantoni, C. et al. J Cancer Res Clin Oncol (2013) 139: 447. doi:10.1007/s00432-012-1327-7



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.


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.


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.


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.


Armed antibodyImmunocytokineL19-TNFPhase I/II trialVascular targetingVasodisruptive therapy

Supplementary material

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

Copyright information

© Springer-Verlag Berlin Heidelberg 2012