The aim of INTERVENE is to develop and test next generation tools for disease prevention, diagnosis, and personalised treatment utilizing the first US-European pool of genomic and health data and integrating longitudinal and disease-relevant -omics data into genetic risk scores. Resulting in unprecedented potential for prediction, diagnosis, and personalised treatments for complex and rare diseases. Some of the largest biobanks in Europe and one in the USA will be securely linked and harmonized in a GDPR-compliant repository with data from more than 1.7 million genomes. INTERVENE will demonstrate the potential and benefits of powerful AI technologies on the next generation of integrative genetic scores (IGS). The clinical and economic benefits of IGS will be evaluated in key disease areas with major public health burden. Here, the newly developed IGS will be taken into clinical environment and their real-world benefits will be evaluated together with clinical experts, European patients advocate groups and medical societies and considering regulatory and ethical implications. Thus, a framework for legally and ethically responsible translation into wider clinical practice will be developed. Moreover, the partners will develop and test the role of IGS in several rare diseases as well as COVID-19 infection and severity. Importantly, to support the application of IGS via public-private partnerships including clinical practitioners, an AI-enabled federated data analysis platform, the ‘IGS4EU’ platform, will be developed for automated IGS generation and interpretation for end-users. Additionally, the IGS4EU platform will allow access of the INTERVENE data and the methodology know-how to the AI community through a competition-based benchmarking environment. In the long term, the IGS4EU platform aims to grow the disease coverage and enable a wide adoption of IGS as a gold standard in clinical research and practice.

Asbestos is one of the major occupational carcinogens. The European Union has an extensive history of protecting workers and consumers against asbestos and even adopted a resolution 2012/2065(INI) ‘on asbestos related occupational health threats and prospects for abolishing all existing asbestos’ last year. Although asbestos is banned, it is still massively present in the built environment. Millions of workers & consumers in the EU were, and still are, for many years exposed to asbestos fibres, despite all measures. Inhalation of even very low quantities of asbestos fibres tremendously increases the risk of developing Malignant Mesothelioma (MM). The IARC reported 8.100 MM deaths in 2010 in the EU. Despite all EU actions, MM incidence is still increasing. MM is a highly fatal disease with a poor median survival time from first signs of illness to death around 12 months despite aggressive treatments. To date there is no curative therapy for MM. MM is considered as an extremely therapy-resistant disease. Chemotherapy consisting of a combination of pemetrexed and cisplatin is considered standard of care with a median survival increase of 3 months (9-12 months). The department of pulmonary diseases of the Erasmus MC, Rotterdam, The Netherlands, in collaboration with international partners, have developed a promising personalised immunotherapy for MM with very limited adverse effects. The first clinical results show a considerably prolonged average survival with limited adverse events (24 months, twice as long). The EMA and the FDA granted this therapy Orphan Designation: autologous dendritic cells pulsed with allogeneic tumour cell lysate for the treatment of malignant mesothelioma (EU: 16 January 2014 - EU/3/13/1229; FDA – US: 06 May 2014). The objective for the project is to deliver the scientific & registration package for market approval by the EMA of a novel immuno therapeutic approach to treat MM. This includes the execution of a phase II/III clinical trial.

The PREFER project will deliver an overview and evaluation of preference elicitation methods to be applied in the entire drug life cycle, i.e. in the early stages of identifying medical needs, in clinical testing, to guide decisions on reimbursement and to make decisions on withdrawal of drugs from the market. A broad array of (combinations of) patient preference methods will be tested prospectively in a large number of case studies. The availability of large patient cohorts will enable to test new methods or deviations from existing methods in a randomized manner, by comparing well-known methods with newer ones. The use of simulation studies will both contribute to smarter design of case studies and to exploring the sensitivity of outcomes of preference studies. Based on discussions with a broad representation of stakeholders e.g. patients, patient organisations, regulatory authorities, HTA bodies and reimbursement agencies, suitable methods will be tested and their contributions to improved decision making will be discussed in recommendations adapted to the needs of all relevant stakeholders. The recommendations from PREFER are expected to lead to changed practices, in that industry will routinely assess whether a preference study would add value at key decision points in the medicinal product life cycle and, if so, implement patient-preference elicitation studies according to the PREFER project recommendations. The PREFER consortium consist of 16 industry partners and 16 academic and SME members including representation from academia, patient organizations, HTA bodies, reimbursement agencies, and project management.

IMMUNOSABR is geared towards opening up a new paradigm in treating metastatic cancer by obtaining clinical proof of concept for a novel bi-modal curative treatment strategy. High precision stereotactic ablative radiotherapy (SABR) is combined with immunotherapy to form a powerful synergistic anti-tumour strategy. The approach relies on the direct cytotoxic effect of SABR, the abscopal effect of radiation observed at distance from the irradiated metastatic site(s), and the effect of the tumour-specific immunocytokine L19-IL2 (watch our animation explaining the concept at https://youtu.be/6wDE6RkrikA). Palliative treatment is the current standard of care for patients with metastatic non small cell lung cancer (NSCLC), unless there is an actionable mutation. By using the concept of limited metastatic disease (≤10 sites, WHO 0-1: “oligo+”) we aim to develop a therapy with curative intent. IMMUNOSABR will gather evidence for the clinical efficacy of our bi-modal treatment strategy in a multicentre randomised phase II study (clinicaltrials.gov no. NCT02735850) in patients with limited metastatic NSCLC. IMMUNOSABR is complemented by two strong biomarker work packages which focus on developing an ambitious personalised biomarker strategy, to identify patients who can benefit from the novel treatment strategy. This includes promising non-invasive imaging techniques and state-of-the-art immunological monitoring approaches on tumour tissue and blood. IMMUNOSABR will spur further development of L19-IL2 as a commercial drug and translate the bi-modal treatment strategy towards clinical implementation.

In the EU, treating patients with prostate (PCa) and kidney cancer (KC) costs more than €6.6 billion annually. Yet, PCa and KC are often managed inadequately, which is associated with high costs and negative consequences such as hospitalisation, psychosocial stress and poorer chances of survival. Diagnostic and therapeutic effectiveness depends on multimodal information, including cancer type, stage, and location as well as the patient’s age and health. Current clinical methods do not effectively use the large amount of mostly unstructured data. The main challenge in developing multimodal models is the lack of access to data sources and missing joint validation of data through collaboration between clinicians and computer scientists. A strength of our consortium is access to multiple sources of medical data, including the largest expert-annotated database for PCa and KC to date. Our overall goal is to develop and deploy marketable data-driven multimodal decision support systems to improve clinical prognosis, patient stratification and individual therapy for patients suffering from PCa or KC, defining a new state-of-the-art for the development of multimodal medical AI applications. We will develop AI models for PCa and KC that incorporate multimodal data, e.g., image data, unstructured medical text notes, laboratory information and biomarkers, and perform a prospective validation of the models in a large prospective multicentric international study. At the same time, we will assess the trust of healthcare professionals and patients in such AI tools and explore how this trust can be increased. By providing improved, personalised diagnosis and prognosis assessment, the multimodal models will ultimately contribute to better patient outcomes and quality of life. The models developed in this study can be used as basis for any use case where imaging and electronic medical records are relevant, as they are easily adaptable and can help combat different types of cancer.