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A phase II study of the cancer vaccine TG4010 alone and in combination with cytokines in patients with metastatic renal clear-cell carcinoma: clinical and immunological findings

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Abstract

MUC1 over-expression in renal clear-cell carcinoma (RCC) is associated with poor prognosis. This phase II study determined the efficacy and tolerability of TG4010, a cancer vaccine based on a modified vaccinia virus expressing MUC1 and interleukin-2, in combination with cytokines, as first-line therapy in metastatic RCC. Thirty-seven patients with progressive, MUC1-positive RCC received TG4010 108 pfu/inj weekly for 6 weeks, then every 3 weeks until progression, when TG4010 was continued in combination with interferon-α2a and interleukin-2. Assessments included clinical response (primary endpoint), safety, time to treatment failure (TTF), overall survival (OS), and immune response. No objective clinical responses occurred. Five of the 27 evaluable patients (18%) had stable disease for >6 months with TG4010 alone and six of 20 patients (30%) had stable disease for >6 months with TG4010 plus cytokines. Median TTF was 4.1, 3.6, and 9.3 months for monotherapy, combination therapy, and overall, respectively. Median OS was 19.3 months for all patients and 22.4 months combination therapy recipients. The most frequent TG4010-related adverse events were minor-to-moderate injection-site reactions, fatigue, and flu-like symptoms. Six of 28 patients showed a MUC1 CD4+ T cell proliferative response during therapy. Anti-MUC1 CD8+ T cells were detected before and after therapy in 3 and 4 patients, respectively. MUC1-specific CD8+ T cell responses were associated with longer survival. Therapy with TG4010 plus cytokines appears to be feasible and well tolerated in patients with metastatic RCC. However, these data should be interpreted with caution, as additional prospective studies are necessary to clarify the clinical efficacy of this therapy.

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Acknowledgments

We thank Andrea Bothwell and Natalie Carter of inScience Communications, a Wolters Kluwer business, who provided copy editing and journal styling prior to and post submission. This work was supported by Ligue contre le Cancer; Pôle de compétitivité Medicen (Immucan); Canceropole d’Ile de France; Centre d’Investigation Clinique en Biotherapie. Assistance Publique des Hôpitaux de Paris (CIC-BT AP-HP).

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Authors and Affiliations

  1. Medical Oncology Department, Georges Pompidou European Hospital, 20 rue Leblanc, 75908, Paris Cedex 15, France

    Stéphane Oudard, Benoit Beuselinck, Eugeniu Banu, Marie-Aude Lefrere-Belda, W. H. Fridman & Eric Tartour

  2. AP-HP, Université Paris Descartes, Paris, France

    Stéphane Oudard, Benoit Beuselinck, Eugeniu Banu, Marie-Aude Lefrere-Belda, W. H. Fridman & Eric Tartour

  3. INSERM U970 PARCC, Paris, France

    Stéphane Oudard & Eric Tartour

  4. Experimental Therapeutics Program, Division of Hematology/Oncology, University of Cincinnati Cancer Institute, 231 Albert Sabin Way ML 0562, Cincinnati, OH, 45267-0562, USA

    Olivier Rixe

  5. Bretonneau Hospital, Tours, France

    Claude Linassier

  6. Cliniques Universitaires Saint-Luc, Brussels, Belgium

    Jean-Pascal Machiels

  7. Lapeyronie Hospital, Montpellier, France

    Marion Baudard

  8. Michallon Hospital, Grenoble, France

    François Ringeisen

  9. Erasme Hospital, Brussels, Belgium

    Thierry Velu

  10. Transgene S.A., Strasbourg, France

    Jean-Marc Limacher & Bruce Acres

  11. Centre d’Investigation Clinique, Georges Pompidou European Hospital, Paris, France

    Michel Azizi

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  1. Stéphane Oudard
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Oudard, S., Rixe, O., Beuselinck, B. et al. A phase II study of the cancer vaccine TG4010 alone and in combination with cytokines in patients with metastatic renal clear-cell carcinoma: clinical and immunological findings. Cancer Immunol Immunother 60, 261–271 (2011). https://doi.org/10.1007/s00262-010-0935-9

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