UV1 vaccination in pembrolizumab-treated patients with recurrent or metastatic head and neck cancer: A randomized multicenter phase 2 trial

Anna Brandt; Konrad Klinghammer; Christoph Schultheiss; Lisa Paschold; Claudia Wickenhauser; Marcus Bauer; Anna Bergqvist; Dennis Hahn; Philippe Schafhausen; Mareike Tometten; Markus Blaurock; Henrike Barbara Zech; Chia-Jung Busch; Andreas Dietz; Urs Müller-Richter; Jürgen Alt; Andreas Boehm; Simone Kowoll; Jörg Steighardt; Alexander Lasch; Ingunn Hagen Westgaard; Marita Westhrin; Alexander Stein; Axel Hinke; Mascha Binder

doi:10.1016/j.medj.2025.100647

UV1 vaccination in pembrolizumab-treated patients with recurrent or metastatic head and neck cancer: A randomized multicenter phase 2 trial

Med. 2025 Apr 11:100647. doi: 10.1016/j.medj.2025.100647. Online ahead of print.

Authors

Anna Brandt¹, Konrad Klinghammer², Christoph Schultheiss³, Lisa Paschold⁴, Claudia Wickenhauser⁵, Marcus Bauer⁵, Anna Bergqvist⁶, Dennis Hahn⁷, Philippe Schafhausen⁸, Mareike Tometten⁹, Markus Blaurock¹⁰, Henrike Barbara Zech¹¹, Chia-Jung Busch¹⁰, Andreas Dietz¹², Urs Müller-Richter¹³, Jürgen Alt¹⁴, Andreas Boehm¹⁵, Simone Kowoll¹⁶, Jörg Steighardt¹⁶, Alexander Lasch¹⁶, Ingunn Hagen Westgaard⁶, Marita Westhrin⁶, Alexander Stein¹⁷, Axel Hinke¹⁸, Mascha Binder¹⁹

Affiliations

¹ Division of Medical Oncology, University Hospital Basel, Basel, Switzerland.
² Department of Hematology and Oncology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
³ Division of Medical Oncology, University Hospital Basel, Basel, Switzerland; Laboratory of Translational Immuno-Oncology, Department of Biomedicine, University of Basel and University Hospital Basel, Basel, Switzerland.
⁴ Department of Internal Medicine IV, Oncology/Hematology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
⁵ Institute of Pathology, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
⁶ Ultimovacs ASA, Oslo, Norway.
⁷ Department of Hematology, Oncology, Stem-Cell Transplantation, and Palliative Care Klinikum Stuttgart, Stuttgart, Germany.
⁸ Department of Oncology, Hematology, and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁹ Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany.
¹⁰ Department of Otorhinolaryngology, Head and Neck Surgery, University Medicine Greifswald, Greifswald, Germany.
¹¹ Department of Otorhinolaryngology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹² Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Leipzig, Germany.
¹³ University Hospital Würzburg, Bavarian Cancer Research Center, Würzburg, Germany.
¹⁴ Department of Internal Medicine III (Hematology, Oncology), University Medical Center Mainz, Mainz, Germany.
¹⁵ Department of Otorhinolaryngology, St. Georg Hospital, Leipzig, Germany.
¹⁶ Coordination Center for Clinical Trials, Medical Faculty, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
¹⁷ Hematology-Oncology Practice Eppendorf (HOPE), Hamburg, Germany.
¹⁸ Clinical Cancer Research Consulting, Düsseldorf, Germany.
¹⁹ Division of Medical Oncology, University Hospital Basel, Basel, Switzerland; Laboratory of Translational Immuno-Oncology, Department of Biomedicine, University of Basel and University Hospital Basel, Basel, Switzerland. Electronic address: mascha.binder@usb.ch.

PMID: 40220758
DOI: 10.1016/j.medj.2025.100647

Abstract

Background: Human telomerase reverse transcriptase is highly expressed in head and neck squamous cell carcinoma (HNSCC). The FOCUS study examines the role of the telomerase-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, 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⁺ HNSCC. A progression-free survival (PFS) rate at 6 months of 40% was deemed promising for further development in a phase 3 setting. The trial was conducted in 10 centers in Germany (this study was registered at ClinicalTrials.gov: NCT05075122).

Findings: From August 2021 to July 2023, 25 patients were enrolled in the pembrolizumab arm and 50 patients in the pembrolizumab + UV1 arm. The PFS rate at 6 months was 40% in the pembrolizumab arm and 30% in the pembrolizumab + UV1 arm. No specific safety signals were observed in the pembrolizumab + UV1 arm apart from a reversible allergic reaction that appeared in one patient. At a median follow-up of 11.3 months, median overall survival was 13.1 months in the pembrolizumab arm and 12.6 months in the pembrolizumab + UV1 arm.

Conclusions: The addition of UV1 to pembrolizumab was safe but did not show an efficacy signal in this study population.

Funding: The legal sponsor of the trial was the University Medical Center Halle (Saale), Germany and was funded by a grant from Ultimovacs.

Keywords: Translation to patients; UV1; head and neck cancer; head and neck squamous cell carcinoma; pembrolizumab.

Associated data

ClinicalTrials.gov/NCT05075122