eligibility_summary
Adults ≥18 with metastatic colorectal adenocarcinoma, RAS/BRAF WT via liquid biopsy, prior 1L cetuximab/irinotecan with CR/PR, >2 mo since last cetuximab, measurable disease, ECOG 0–1, life expectancy >12 wks, adequate marrow/liver/renal, contraception. Exclude: contraindication to study drugs, other active cancer, pregnancy/lactation, recent trial, significant immunosuppression, infection (incl HIV), active autoimmune, prior transplant, severe hypersensitivity, >G1 toxicity, major CV disease, keratitis, serious comorbidity, substance abuse, legal incapacity.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
NCT06321081 tests a rechallenge “ICE” regimen in RAS/BRAF–wild-type metastatic colorectal cancer: 1) Irinotecan (CPT‑11), a cytotoxic chemotherapy prodrug of SN‑38 that inhibits topoisomerase I, causing DNA replication stress and tumor cell death. 2) Cetuximab, a chimeric IgG1 anti‑EGFR monoclonal antibody that blocks EGFR signaling (RAS/RAF/MEK/ERK and PI3K/AKT) and can induce NK cell–mediated ADCC, efficacy depends on RAS/BRAF WT status. 3) Envafolimab, a subcutaneous humanized single‑domain monoclonal antibody PD‑L1 inhibitor that restores T‑cell antitumor activity by blocking PD‑1/PD‑L1. Targets/pathways: tumor Topo I, EGFR-driven signaling on CRC cells, and the immune checkpoint axis in the tumor microenvironment.