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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)

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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.

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Acknowledgments

This study was sponsored by Merck-Serono SA – Geneva, Switzerland. Writing support was provided by Idera pharmaceuticals.

Ethical standards

The authors state that the experiments described in this manuscript comply with the current laws of the country in which they were performed.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Author notes

  1. U. Forssmann

    Present address: Bayer Pharma AG, Berlin, Germany

Authors and Affiliations

  1. Zala Megyei Kórház Külsokórház Onkológia Osztály, Zalaegerszeg, Pozva, Hungary

    A. Ruzsa

  2. St James’s Institute of Oncology, Leeds, UK

    M. Sen

  3. Velindre Cancer Centre, Cardiff, UK

    M. Evans

  4. Christie Hospital, Manchester, UK

    L. W. Lee

  5. Általános Orvostudományi Kar. Onkoterápiás Klinika, Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ, Szeged, Hungary

    K. Hideghety

  6. Ghent University Hospital, Ghent, Belgium

    S. Rottey

  7. Oblastní nemocnice Kladno, Kladno, Czech Republic

    P. Klimak

  8. Bulovce Ustav radiačni onkologie, Fakultni nemocnice Na, Praha, Czech Republic

    P. Holeckova

  9. Centre Léon Bérard, Lyon, France

    J. Fayette

  10. Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Rendelointézet, Szolnok, Hungary

    T. Csoszi

  11. Josa Andras Teaching Hospital, Nyiregyhaza, Hungary

    J. Erfan

  12. Merck Serono SA, Geneva, Switzerland

    T. Goddemeier

  13. Idera Pharmaceuticals, Cambridge, MA, USA

    A. Bexon

  14. Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK

    C. Nutting

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NA EMD 1201081 Study Group

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Correspondence to C. Nutting.

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Ruzsa, A., Sen, M., Evans, M. et al. 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). Invest New Drugs 32, 1278–1284 (2014). https://doi.org/10.1007/s10637-014-0117-2

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  • DOI: https://doi.org/10.1007/s10637-014-0117-2

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