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

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.