The CARE1 pragmatic clinical trial was designed to determine the optimal treatment combination for patients with metastatic kidney cancer, using a specific biomarker. The trial, funded by the European grant Horizon 2020, will use existing approved treatments with the aim of selecting the best combination for each patient. The trial will also build a large consortium with clinical data and prospective follow-up, allowing for further projects to be designed to understand the disease’s biology and the biomarker to guide treatment strategies. The trial will involve 8 European countries and about 100 centers, treating 1200 patients and collecting blood tumor samples and clinical data. The anticipated impact of the CARE1 study is to change the standard of care by demonstrating that the use of a biomarker can increase overall survival and provide more defined guidelines for patients.