eligibility_summary
Inclusion: Adults ≥18 with metastatic BRAF V600E CRC, after 2L encorafenib+cetuximab with CR/PR/SD ≥3 mo then progression, ECOG 0–1, life ≥3 mo, FOLFIRI‑fit, adequate marrow/renal/hepatic/cardiac, archival tissue, contraception/neg pregnancy test. Exclusion: PD on EC, drug CIs, DPYD or UGT1A1/Gilbert, recent major cardiac or long QT, active infection incl HIV/HBV/HCV, symptomatic CNS mets, >G2 toxicity, CYP3A4 inhibitors/St John’s wort, serious illness/cancer, pregnancy/lactation or no contraception.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase II single-arm trial in BRAF V600E metastatic colorectal cancer progressing on prior encorafenib+cetuximab. Tests encorafenib (oral small-molecule BRAF V600E inhibitor) plus cetuximab (anti-EGFR IgG1 monoclonal antibody) continued beyond progression, combined with FOLFIRI: irinotecan (camptothecin prodrug, topoisomerase I inhibitor), 5-fluorouracil (pyrimidine antimetabolite inhibiting thymidylate synthase and RNA/DNA synthesis), and folinic acid/leucovorin (potentiates 5-FU). Targets/pathways: BRAF V600E-mutant colorectal tumor cells, EGFR–RAS–RAF–MEK–ERK (MAPK) signaling, with dual EGFR and BRAF blockade to counter feedback MAPK reactivation, DNA replication and nucleotide synthesis in rapidly dividing tumor cells via topo I inhibition and TS blockade. Primary endpoint: 6-month PFS rate.