In this respect, CRICKET and CAVE phase II were the first prospective clinical trials that reported clinically meaningful antitumor activity with an acceptable safety profile of rechallenge therapy with cetuximab in combination with the topoisomerase I inhibitor irinotecan or with the anti‐programmed death ligand 1 (PD‐L1) monoclonal antibody avelumab, respectively, in a subset of patients with RAS WT mCRC [i.e., with RAS/BRAF WT disease at baseline, as assessed by liquid biopsy analysis of circulating tumor DNA, (ctDNA)].11, 12. This evidence concerns the gene BRAF and neoplasm.