UV1 cancer vaccine in pembrolizumab-treated patients with recurrent or metastatic PD-L1 positive head and neck squamous cell carcinoma: results from the randomized phase 2 FOCUS trial

medRxiv

Abstract

Abstract Background Human telomerase reverse transcriptase (hTERT) is highly expressed (75-100%) in head and neck squamous cell carcinoma (HNSCC). The FOCUS study examines the role of the hTERT-directed vaccine UV1 in combination with pembrolizumab in patients with recurrent or metastatic (R/M) HNSCC. Methods The FOCUS trial, a two-armed, open-label, non-comparative, randomized, multicenter phase 2 study, was designed to assess the efficacy and feasibility of UV1 as an add-on to pembrolizumab in the first-line treatment of patients with R/M PD-L1 positive HNSCC. A progression-free survival rate at 6 months (PFSR@6) of 40% was deemed promising for further development in a phase 3 setting. The trial was conducted in 10 centers in Germany. Results From August 2021 to July 2023, 25 patients were enrolled in the calibration arm A and 50 patients in the UV1 arm B. Median age was 65 years and 18% of patients had an ECOG performance score of 2. The PFSR@6 was 30% in the UV1 arm. No specific safety signals were observed in the UV1 arm apart from a reversible allergic reaction that appeared in one patient. At a median follow-up of almost one year (11.3 months), median overall survival was 13.1 months in the calibration arm A and 12.6 months in the UV1 arm B. Clinical trial identification number NCT05075122 . Conclusions The addition of UV1 to pembrolizumab was safe but did not show an efficacy signal in this study population.

Authors 23

1. Anna Paula Brandt

   University of Basel · University Hospital of Basel

   Affiliation as printed

   Division of Medical Oncology, University Hospital Basel, Basel, Switzerland;

   Division of Medical Oncology, University Hospital Basel, Basel, Switzerland

2. Konrad Friedrich Klinghammer

   Humboldt-Universität zu Berlin · Charité - Universitätsmedizin Berlin

   Affiliation as printed

   Department of Hematology and Oncology, Campus Benjamin Franklin, Charite - Universitaetsmedizin Berlin, Corporate Member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, and Berlin Institute of Health, Berlin, Germany;

   Department of Hematology and Oncology, Campus Benjamin Franklin, Charite - Universitaetsmedizin Berlin, Corporate Member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, and Berlin Institute of Health, Berlin, Germany

3. Christoph Schultheiß

   University of Basel · University Hospital of Basel

   Affiliation as printed

   Laboratory of Translational Immuno-Oncology, Department of Biomedicine, University and University Hospital Basel, Basel, Switzerland;

   Laboratory of Translational Immuno-Oncology, Department of Biomedicine, University and University Hospital Basel, Basel, Switzerland

4. Lisa Paschold

   Martin Luther University Halle-Wittenberg

   Affiliation as printed

   Department of Internal Medicine IV, Oncology/Hematology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany;

   Department of Internal Medicine IV, Oncology/Hematology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany

5. Claudia Wickenhauser

   Martin Luther University Halle-Wittenberg · University Hospital in Halle

   Affiliation as printed

   Institute of Pathology, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany;

   Institute of Pathology, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany

6. Marcus Bauer

   Martin Luther University Halle-Wittenberg · University Hospital in Halle

   Affiliation as printed

   Institute of Pathology, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany;

   Institute of Pathology, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany

7. Dennis Hahn

   Klinikum Stuttgart

   Affiliation as printed

   Klinikum Stuttgart, Stuttgart, Germany; Dept. of Hematology, Oncology, Stem-Cell Transplantation and Palliative Care;

   Dept. of Hematology, Oncology, Stem-Cell Transplantation and Palliative Care

   Klinikum Stuttgart, Stuttgart, Germany

8. Philippe Schafhausen

   University Medical Center Hamburg-Eppendorf

   Affiliation as printed

   Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;

   Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9. Mareike Tometten Aachen Medical Faculty Department of Hematology, Oncology

   RWTH Aachen University

   Affiliation as printed

   Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany;

   Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany

10. Markus Blaurock

    Universitätsmedizin Greifswald · Universität Greifswald

    Affiliation as printed

    Department of Otorhinolaryngology, Head and Neck Surgery, University Medicine Greifswald, Greifswald, Germany;

    Department of Otorhinolaryngology, Head and Neck Surgery, University Medicine Greifswald, Greifswald, Germany

11. Henrike Barbara Zech

    University Medical Center Hamburg-Eppendorf

    Affiliation as printed

    Department of Otorhinolaryngology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;

    Department of Otorhinolaryngology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

12. Chia‐Jung Busch

    Universitätsmedizin Greifswald · Universität Greifswald

    Affiliation as printed

    Department of Otorhinolaryngology, Head and Neck Surgery, University Medicine Greifswald, Greifswald, Germany;

    Department of Otorhinolaryngology, Head and Neck Surgery, University Medicine Greifswald, Greifswald, Germany

13. Andreas Dietz

    Leipzig University

    Affiliation as printed

    Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Leipzig, Germany;

    Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Leipzig, Germany

14. Urs D. A. Müller-Richter

    Universitätsklinikum Würzburg

    Affiliation as printed

    University Hospital Würzburg , Bavarian Cancer Research Center (BZKF) , Würzburg , Germany

    University Hospital Wuerzburg, Bavarian Cancer Research Center (BZKF), Wuerzburg, Germany

15. Jürgen August Alt

    University Medical Center of the Johannes Gutenberg University Mainz

    Affiliation as printed

    Department of Internal Medicine III (Hematology, Oncology), University Medical Center Mainz, Mainz, Germany;

    Department of Internal Medicine III (Hematology, Oncology), University Medical Center Mainz, Mainz, Germany

16. Andreas Boehm

    Klinikum St. Georg

    Affiliation as printed

    Department of Otorhinolaryngology, St. Georg Hospital, Leipzig, Germany;

    Department of Otorhinolaryngology, St. Georg Hospital, Leipzig, Germany

17. Simone Kowoll

    Martin Luther University Halle-Wittenberg

    Affiliation as printed

    Coordination Center for Clinical Trials, Medical Faculty, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany;

    Coordination Center for Clinical Trials, Medical Faculty, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany

18. Jörg Steighardt

    Martin Luther University Halle-Wittenberg

    Affiliation as printed

    Coordination Center for Clinical Trials, Medical Faculty, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany;

    Coordination Center for Clinical Trials, Medical Faculty, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany

19. Ingunn Hagen Westgaard

    Ultimovacs (Norway)

    Affiliation as printed

    Ultimovacs ASA, Oslo, Norway;

    Ultimovacs ASA, Oslo, Norway

20. Marita Westhrin

    Ultimovacs (Norway)

    Affiliation as printed

    Ultimovacs ASA, Oslo, Norway;

    Ultimovacs ASA, Oslo, Norway

21. Alexander Stein
    Affiliation as printed

    Hematology-Oncology Practice Eppendorf (HOPE), Hamburg, Germany;

    Hematology-Oncology Practice Eppendorf (HOPE), Hamburg, Germany

22. Axel Hinke
    Affiliation as printed

    Clinical Cancer Research Consulting (CCRC), Duesseldorf, Germany

23. Mascha Binder corresponding

    University of Basel · University Hospital of Basel

    Affiliation as printed

    Division of Medical Oncology, University Hospital Basel, Basel, Switzerland;

    Division of Medical Oncology, University Hospital Basel, Basel, Switzerland