Phase II Study of ctDNA-guided Encorafenib Plus Cetuximab Retreatment in Patients BRAF V600E Mutated mCRC

This is a proof-of-concept, multicenter, open-label, single arm one-stage phase II trial of a ctDNA-guided retreatment with encorafenib plus cetuximab for mCRC patients bearing the BRAFV600E mutation and with the key following characteristics: * initial benefit and then secondary resistance to a previous exposure to encorafenib and cetuximab with or without chemotherapy; * only one subsequent intervening anti-BRAF and anti-EGFR-free line of therapy; * confirmed BRAFV600E mutated status and no detectable mutations in KRAS, NRAS, MAP2K1 and no amplification of MET in ctDNA at the time of retreatment; Eligible patients will receive Encorafenib 300 mg once daily (four 75 mg oral capsules) and Cetuximab 500 mg/sqm iv infusion every 14 days.Treatment will be delivered in 28-day cycles until disease progression, unacceptable toxic effects, withdrawal of consent, initiation of subsequent anticancer therapy, or death.