Figure 4

Schematic overview of the Tracking Non-small Cell Lung Cancer Evolution Through Therapy (TRACERx) observational cohort study and how this is linked with the Deciphering Anti-tumour Response and evolution With INtratumour heterogeneity (DARWIN) trials program. Multi-region sampling with ultra-deep 500x coverage whole-exome sequencing (WES) will be used to characterize tumor heterogeneity. Tumor heterogeneity and clonal dynamics may affect the response to precision drugs. Only patients from the TRACERx observational study will be eligible for a DARWIN trial. Therefore, in comparison to other molecularly stratified studies TRACERx & DARWIN provide a unique opportunity to study the affect of intratumour heterogeneity and clonal architecture on patient outcome. The effect of tumor heterogeneity and mutational burden on anti-tumor immunity will also be assessed through an immunotherapy arm. Bx, biopsy; CTC, circulating tumor cell; cfDNA, cell free DNA; IMT, immunotherapy; ITH, intertumor heterogeneity; NSCLC, non-small cell lung cancer; PrM, precision medicine; SOC, standard of care.