Multimodal Approach Targeting treatment Refractory cancers usIng neXt generation technologies and trials

More than 38 000 patients were diagnosed with cancer in Norway in 2023. Although most patients recover, cancer is still the number one cause of death in Norway and more than 11,000 died of the disease last year. In recent years, we have seen important improvements in several cancer diagnoses, with improved prognosis, but unfortunately some cancers are still very difficult to treat effectively. Moreover, many patients live substantially longer, but also experience long-term side effects from the treatment or the disease. MATRIX, the Norwegian Centre for Clinical Cancer Research, is a national research centre with an over-all ambition to help patients with hard-to-treat cancers to live longer with better quality of life. In addition to survival, quality of life, maintaining functional capacity and relief from symptoms are of the utmost importance to all cancer patients. Improved methods for diagnostics and therapy as well as systematic and effective methods for symptom management and follow-up need to be developed further. MATRIX aims to implement systematic digital symptom mapping and are in the process of developing new, digital patient-centred care pathways. The digital solution is being developed in collaboration with DNV Imatis, and four hospitals in Norway (Ålesund, Førde, Skien and Oslo) are currently involved in the process. A prototype has been tested in 2024. To improve patient outcomes, one main research focus in MATRIX is to develop new diagnostic tools. This includes drug sensitivity screening, treating cancer cells from the patient with different drugs, to identify the most effective ones for the specific patient. Use of liquid biopsies, in-depth analyses of proteins and other molecules is also being investigated to enable individualized treatment. In addition, MATRIX works on developing and use imaging and artificial intelligence in diagnosis and treatment. An overarching goal in MATRIX is to offer as many patients as possible treatment in a clinical trial. A national network, that includes 15 hospitals with cancer departments, is established, and the Centre has a mechanism for supporting hospitals that treat patients in MATRIX-supported clinical trials. Patient-centred treatment is also part of the clinical studies connected to MATRIX. The Centre will end of 2024 open a new national clinical trial, MATRIX-RARE, where patients with rare cancer types that are difficult to treat, will be offered precision medicine in earlier treatment lines. Initially, the study will include anaplastic thyroid cancer, salivary gland carcinoma, glioblastoma multiforme, cholangiocarcinoma and small intestine cancers, Other subgroups of patients with rare and aggressive cancer types will be considered if data from IMPRESS-Norway shows that the patients can benefit from precision oncology. MATRIX has been operational for two years. In 2024, two new researchers have been recruited to Stavanger University Hospital and the University Hospital of North Norway, respectively. In addition, MATRIX is in collaboration with the University of Oslo in the process of recruiting a professor (20% position) to the UiO Growth House. This position will include both mentoring of researchers and teaching about the design and implementation of clinical trials. Moreover, a digital registration form where partners in the Centre can register new clinical trials and apply for support, is available from the MATRIX website. The national management team have monthly meetings were potential trials are discussed. The MATRIX Board is chaired by Sigbjørn Smeland, head of the Division of Cancer Medicine at Oslo University Hospital. Furthermore, the Centre's Scientific Advisory Board, with five internationally renowned clinicians and researchers with expertise in precision medicine and cancer research, held its first start-up meeting in 2024. MATRIX has in collaboration with OsloMet also developed and established a new master course (MATVIT5800): Introduction to clinical studies for healthcare personnel. The first course in the fall 2023 was fully booked with a waiting list and with participants from all over the country. The course in 2024 is also fully booked with a waiting list, and OsloMet is now trying to expand the number of students to this course. MATRIX has also, in collaboration with OUH and ACTA Oncologica, established a symposium that is organized every second year. After the Nordic Precision Cancer Medicine Symposium held in the fall 2023, a special issue on precision medicine was published in Acta Oncologica in 2024 with publications from several of the participants at the conference: https://medicaljournalssweden.se/actaoncologica/article/view/41063/46593 The next NPCM Symposium will take place in Oslo September 15-17 2025. News and other information from MATRIX is being published regularly on the Centre's website: http://www.matrix-fkb.no The Centre also uses social media and sends out quarterly newsletters.

In MATRIX, we will take advantage of on-going large national precision cancer medicine initiatives, the national tumor groups, the national initiatives in patient-centered care and the unique infrastructure for clinical trials to facilitate development and implementation of next generation cancer care. Diagnostics: We will develop new diagnostic methods in molecular profiling (-omics), drug sensitivity screening, immune system characterization, PROMs and AI tools for analysis of images and clinical real-world data. Collaboration with the newly established national infrastructure for precision diagnostics will enable systematically and rapid testing of the clinical benefit of diagnostic tools in the ongoing precision medicine trial IMPRESS-Norway, which will be further developed in MATRIX. Treatment: We will develop and test new treatment strategies in clinical trials. We will test novel combination of drugs based on newly establish diagnostic tools to overcome resistance. Integration with the newly establish Centre for Advanced Cell Therapy will allow us to test novel approaches for cell therapy. Patient Centered Care: Experience from the ongoing precision medicine initiatives in Norway clearly shows the need for tools that ensures that patient preferences and patient communication is integrated into the treatment decision. We will therefore take advantage of ongoing research project on e-Health solutions for integrating patient preferences into the decision process. Participation of the established large clinical trial network of MATRIX involving most hospitals in Norway with a cancer division will ensure access for patients and competence building across the country. A clinical trial engine will be established to ensure competence building (regulatory, logistics etc.) for advanced clinical trials (e.g. cell therapy) to facilitate future trial capacity and establishing Norway at the forefront of coming developments in cancer therapy.