Investigational New Drugs

, Volume 32, Issue 6, pp 1278–1284

Phase 2, open-label, 1:1 randomized controlled trial exploring the efficacy of EMD 1201081 in combination with cetuximab in second-line cetuximab-naïve patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN)

  • A. Ruzsa
  • M. Sen
  • M. Evans
  • L. W. Lee
  • K. Hideghety
  • S. Rottey
  • P. Klimak
  • P. Holeckova
  • J. Fayette
  • T. Csoszi
  • J. Erfan
  • U. Forssmann
  • T. Goddemeier
  • A. Bexon
  • C. Nutting
  • NA EMD 1201081 Study Group
PHASE II STUDIES

DOI: 10.1007/s10637-014-0117-2

Cite this article as:
Ruzsa, A., Sen, M., Evans, M. et al. Invest New Drugs (2014) 32: 1278. doi:10.1007/s10637-014-0117-2

Summary

Aim: to determine whether EMD 1201081, a TLR9 agonist, added to cetuximab had antitumor activity in second-line recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) Methods: this was a phase 2, open-label, randomized trial of EMD 1201081 0.32 mg/kg subcutaneously weekly plus cetuximab (combination) vs cetuximab monotherapy (control) in cetuximab-naïve patients with R/M SCCHN who progressed on 1 cytotoxic regimen. Crossover to combination was permitted after progression Results: objective response rate in both arms was 5.7 % (95 % CI 1.2–15.7 %) by independent assessment. Disease control was 37.7 % for patients on combination (24.8–52.1 %) and 43.4 % on control (29.8–57.7 %). Neither independent nor investigator assessments showed significant differences between study arms. Median progression-free survival was 1.5 months (1.3–2.6) for patients on combination, and 1.9 months (1.5–2.9) on control.

The most frequent adverse events in the combination arm were rash (29.6 %), acneiform dermatitis (22.2 %), and injection site reactions (20.4 %). Grade 3/4 dyspnea and hypokalemia were more frequent with cetuximab monotherapy (7.5 % and 5.7 % vs 1.9 % each, respectively), and grade 3/4 respiratory failure and disease progression were more frequent with combination (5.6 % each vs 1.9 % each) Conclusion: EMD 1201081 was well tolerated combined with cetuximab, but there was no incremental clinical efficacy.

Keywords

Head and neck cancerToll-like receptor 9Epidermal growth factor receptor-neu receptorCetuximabOligonucleotideRecurrent metastaticSquamous cell carcinomaRandomized phase 2

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • A. Ruzsa
    • 1
  • M. Sen
    • 2
  • M. Evans
    • 3
  • L. W. Lee
    • 4
  • K. Hideghety
    • 5
  • S. Rottey
    • 6
  • P. Klimak
    • 7
  • P. Holeckova
    • 8
  • J. Fayette
    • 9
  • T. Csoszi
    • 10
  • J. Erfan
    • 11
  • U. Forssmann
    • 12
  • T. Goddemeier
    • 13
  • A. Bexon
    • 14
  • C. Nutting
    • 15
  • NA EMD 1201081 Study Group
    • 16
  1. 1.Zala Megyei Kórház Külsokórház Onkológia OsztályZalaegerszegHungary
  2. 2.St James’s Institute of OncologyLeedsUK
  3. 3.Velindre Cancer CentreCardiffUK
  4. 4.Christie HospitalManchesterUK
  5. 5.Általános Orvostudományi Kar. Onkoterápiás KlinikaSzegedi Tudományegyetem Szent-Györgyi Albert Klinikai KözpontSzegedHungary
  6. 6.Ghent University HospitalGhentBelgium
  7. 7.Oblastní nemocnice KladnoKladnoCzech Republic
  8. 8.Bulovce Ustav radiačni onkologieFakultni nemocnice NaPrahaCzech Republic
  9. 9.Centre Léon BérardLyonFrance
  10. 10.Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-RendelointézetSzolnokHungary
  11. 11.Josa Andras Teaching HospitalNyiregyhazaHungary
  12. 12.Bayer Pharma AGBerlinGermany
  13. 13.Merck Serono SAGenevaSwitzerland
  14. 14.Idera PharmaceuticalsCambridgeUSA
  15. 15.Royal Marsden HospitalLondonUK
  16. 16.This study was sponsored by Merck-Serono SAGenevaSwitzerland