The co-clinical trial concept stimulates a rethink of the entire drug development and drug approval process. There is a focus on interrogating mechanisms of response and resistance as well as strategies to increase response and overcome resistance based on PDX models. Currently, there are limited options to analyze and integrate real-time information of ongoing clinical trials, partly by the inherent nature of the setup of a clinical trial, partly due to a shortness of biologically available tissue. By simultaneously establishing and treating PDXs of a patient enrolled in a clinical trial with a new agent, underlying mechanisms can be studied, novel combination strategies can be evaluated and potential biomarkers can be identified. The initiation and implementation of the co-clinical trial project will ensure that the transition of preclinical drug evaluation data to the clinics will occur quicker.