ASPiRATION 2 Liquid (ASPiRATION-2L) will establish a national framework for precision medicine in lung cancer through the implementation of using serial blood-based ctDNA testing (called “liquid biopsy’) to guide treatments following progression on targeted therapies. ctDNA results will be reviewed by an expert tumour molecular board to inform clinical decision making on next line treatment. The option for further ctDNA sampling and review is available for participants should progression recur, which will enable treatment to be tailored based on the tumour’s changing molecular profile.