Squamous cell carcinomas (SCCs) may originate from various locations in the body, are sometimes related to HPV (Human Papilloma Virus) infection and are shown to harbour similar molecular alterations justifying a common therapeutic strategy. In 2017, for the first time in the history of oncology, a drug has been approved by the FDA (Food and Drug Administration) across tumor types based on a molecular alteration (i.e. pembrolizumab in MSI-high tumors). So far, we have infrequently been able to cure late stage cancers with medical treatments. Late stage cancers acquire multiple drug resistance mechanisms and thus a combination of drugs may be needed for treatment, making the discovery of a cure for late stage disease extremely challenging. Integration of multiple molecular data with patients clinical history is today crucial to apprehend new mechanisms related to drug efficacy or resistance. Via the PEVOSQ basket trial with pembrolizumab in combination with vorinostat in patients with late stage SCC of various locations and the assessment of molecular and clinical data at different time points, we aim to: 1) explore the modifications of immune-related and molecular-epigenetic biomarkers; 2) build a database integrating molecular and clinical profiles for treatment decision; 3) develop long-term standards alongside other strategies for data collection and management to produce high-quality data with appropriate metadata and provenance, and 4) set a module for patients inclusion in clinical trials. Our ambition is to enable investigators to leverage all possible data and tools in the effort to accelerate biomedical discoveries, therapies and cures driving the development of data infrastructure and data science capabilities through collaborative research based on a real life prospective clinical trial. With this project we will provide a proof-of-concept for the importance of integrating molecular data to accelerate patient enrollment in clinical trials.