A novel immunotherapy for cancer

This project aims to develop Ultimovacs` universal cancer vaccine UV1 as a novel therapy in combination with standard immune checkpoint therapy (CPI) for head and neck cancer (HNC). The commercial project partner Bio-Me AS will develop a diagnostic test based on their platform technology for gut microbiome analysis, and the project aims to additionally identify novel diagnostic/prognostic products for patient selection and treatment response monitoring based on immunological markers and tumor markers. HNC is ranked as the 9th most frequent cancer worldwide. HNC is a group of cancers that arise from several different sites, including the nasal cavity, larynx, pharynx, lips, and oral cavity. Untreated recurrent/metastatic disease has an extremely poor prognosis with median overall survival (mOS) of about 4 months. During the last decade, immunotherapy with checkpoint inhibitors (CPIs) has revolutionized cancer treatment. CPIs are drugs that take ?brakes? off immune cells that are reactive against tumor cells. CPIs thereby enhance the underlying spontaneously generated anti-tumor response. CPIs have demonstrated lasting clinical benefit (better overall survival) in many cancer types, but in HNC the rate of patients responding to CPIs remain limited compared to other cancer types. Even with CPIs adopted as a new regimen, HNC patients therefore suffer from marginally effective therapy options and there is still a high level of unmet medical need for novel treatment strategies offering effective and safe treatment options. The lack of clinically validated biomarkers for CPIs in HNC significantly hampers early disease detection and evidence-based treatment decisions. The underlying idea of this project is that the combination of the UV1 vaccine with a CPI will provide a novel mechanism of action (MoA) addressing the shortcomings of CPIs in HNC. UV1 activates immune cells to recognize tumor cells and provide a broader basis for efficacy of the CPI. This mechanism of action of the combination will induce novel biological signatures to be used as biomarkers for patient selection and disease-monitoring in HNC. The current project relates to the FOCUS trial, a Phase II randomized clinical trial that will evaluate UV1 in 75 patients with recurrent or metastatic head and neck cancer who will be treated with standard of care therapy pembrolizumab. Biological sample material collected from all patients is used as basis for the biomarker-identification analyses.

This project aims to develop Ultimovacs` universal cancer vaccine UV1 as a novel therapy for head and neck squamous cell carcinoma (HNSCC), a cancer type where current immunotherapy options have marginal clinical effect. The project additionally aims to develop novel non-invasive biomarker tools for patient selection and treatment response monitoring. The underlying idea of the project is that the combination of the UV1 vaccine with a standard of care immunotherapy in the form of pembrolizumab will provide a novel mechanism of action and novel biological signatures to be developed as biomarkers for HNSCC. The backbone of the project is an investigator-initiated, randomized, phase II clinical trial that will be conducted at 10 sites across Germany. The trial will be led by principal investigator Prof. Mascha Binder, M.D., Medical Director and Head of the Immunological Tumor Group at University Medicine Halle, Germany. Prof. Binder is a renowned oncology clinician and researcher specializing in the analysis of immuno-oncology treatments and their interaction with tumor tissues. A total of 75 patients will be randomized 2-to-1 so that 50 patients will receive UV1 and pembrolizumab and 25 patients will receive pembrolizumab alone. The primary endpoint of the study is the progression-free survival rate at 6 months. Biological material (faeces, blood and tumor tissue) will be collected and stored in a biobank forming the basis for an extensive translational research program, aiming to identify microbiota signatures in feces and immune- and tumor signatures in blood to be developed further into biomarker tools for patient selection and treatment response monitoring.