Tolerability and efficacy of the cancer vaccine UV1 in patients with recurrent or metastatic PD-L1 positive head and neck squamous cell carcinoma planned for first-line treatment with pembrolizumab - the randomized phase 2 FOCUS trial

Anna Brandt; Christoph Schultheiss; Konrad Klinghammer; Philippe Schafhausen; Chia-Jung Busch; Markus Blaurock; Axel Hinke; Mareike Tometten; Andreas Dietz; Urs Müller-Richter; Dennis Hahn; Jürgen Alt; Alexander Stein; Mascha Binder

doi:10.3389/fonc.2024.1283266

Tolerability and efficacy of the cancer vaccine UV1 in patients with recurrent or metastatic PD-L1 positive head and neck squamous cell carcinoma planned for first-line treatment with pembrolizumab - the randomized phase 2 FOCUS trial

Front Oncol. 2024 Feb 7:14:1283266. doi: 10.3389/fonc.2024.1283266. eCollection 2024.

Authors

Anna Brandt¹, Christoph Schultheiss^{1

2}, Konrad Klinghammer³, Philippe Schafhausen⁴, Chia-Jung Busch⁵, Markus Blaurock⁵, Axel Hinke⁶, Mareike Tometten⁷, Andreas Dietz⁸, Urs Müller-Richter⁹, Dennis Hahn¹⁰, Jürgen Alt¹¹, Alexander Stein¹², Mascha Binder^{1

2}

Affiliations

¹ Division of Medical Oncology, University Hospital Basel, Basel, Switzerland.
² Laboratory of Translational Immuno-Oncology, Department of Biomedicine, University and University Hospital Basel, Basel, Switzerland.
³ Department of Hematology and Oncology, Charité - Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
⁴ Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁵ Department of Otorhinolaryngology, Head and Neck Surgery, University Medicine Greifswald, Greifswald, Germany.
⁶ Clinical Cancer Research Consulting (CCRC), Düsseldorf, Germany.
⁷ Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany.
⁸ Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Leipzig, Germany.
⁹ University Hospital Würzburg, Bavarian Cancer Research Center (BZKF), Würzburg, Germany.
¹⁰ Department of Hematology, Oncology, Stem-Cell Transplantation and Palliative Care, Klinikum Stuttgart, Stuttgart, Germany.
¹¹ Department of Internal Medicine III (Hematology, Oncology), University Medical Center Mainz, Mainz, Germany.
¹² Hematology-Oncology Practice Eppendorf (HOPE), Hamburg, Germany.

Abstract

Background: Globally, head and neck squamous cell carcinoma (HNSCC) is the seventh most common malignancy. Despite aggressive multimodal treatment approaches, recurrent and/or metastatic (R/M) disease develops in >50% of patients. In this setting, pembrolizumab was approved for patients with PD-L1 expression. However, response rates with checkpoint inhibitor monotherapy remain limited and strategies to strengthen tumor-directed immune responses are needed.

Objective: The FOCUS trial is designed to estimate the effectiveness of UV1 vaccination in combination with pembrolizumab versus pembrolizumab as a single agent in patients with R/M HNSCC.

Methods and analysis: The FOCUS trial is a two-armed, randomized, multicenter phase II study which was designed to evaluate the efficacy and feasibility of the hTERT-targeted cancer vaccine UV1 as add-on to pembrolizumab in the 1st line treatment of patients with R/M PD-L1 positive (combined positive score ≥1) HNSCC. Secondary objectives are the exploration of patient subgroups most likely deriving benefit from this novel combination and the establishment of liquid biopsy tumor monitoring in HNSCC.

Ethics and dissemination: This clinical study was designed and will be conducted in compliance with Good Clinical Practice and in accordance with the Declaration of Helsinki. It is intended to publish the results of this study in peer-reviewed scientific journals and to present its content at academic conferences.

Conclusions: A significant number of patients with R/M HNSCC are frail and may not tolerate chemotherapy, these patients may only be suitable for pembrolizumab monotherapy. However, long term disease stabilizations remain the exception and there is a need for the development of efficacious combination regimens for this patient population. The FOCUS study aims to optimize treatment of R/M HNSCC patients with this promising new treatment approach.

Clinical trial registration: https://clinicaltrials.gov/study/NCT05075122, identifier NCT05075122.

Keywords: UV1; cancer immunotherapy; cancer vaccine; head and neck squamous cell carcinoma (HNSCC); pembrolizumab.

Associated data

ClinicalTrials.gov/NCT05075122

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was funded by the University Hospital Basel.