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

BackgroundHuman 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. MethodsThe 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. ResultsFrom 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. ConclusionsThe addition of UV1 to pembrolizumab was safe but did not show an efficacy signal in this study population.