eligibility_summary
Adults 18-75, ECOG 0-1, >=3 mo survival, unresectable metastatic colorectal cancer, MSI-L/MSS. Only prior 1L oxaliplatin (FOLFOX/CAPOX), measurable disease. Provide 15 FFPE slides, adequate marrow, renal (CrCl>=50, proteinuria<=1+), hepatic (TBil/AST/ALT within limits, ALB>=28). Exclude MSI-H/dMMR, BRAF mut, recent cancers, prior immunotherapy, active autoimmune/IBD, immunodeficiency/HIV, TB/syphilis, transplant, ILD, infection, active HBV/HCV (controlled HBV ok) recent/planned major surgery.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Single-arm Phase 2 testing AK104 (cadonilimab), a bispecific immune-checkpoint monoclonal antibody that blocks PD-1 and CTLA-4, plus FOLFIRI chemotherapy and either cetuximab or bevacizumab as second-line therapy for MSS metastatic colorectal cancer, with biologic selection guided by RAS status (cetuximab for RAS WT, bevacizumab for RAS mutant). Mechanisms: AK104 restores antitumor T-cell activity by inhibiting PD-1/CTLA-4 signaling. Cetuximab is an anti-EGFR IgG1 mAb that blocks EGFR signaling on tumor cells. Bevacizumab is an anti-VEGF-A mAb that inhibits angiogenesis via VEGF pathway blockade. FOLFIRI: 5-FU (thymidylate synthase inhibitor) + irinotecan (topoisomerase I inhibitor) + leucovorin (enhances 5-FU). Targets: T-cell checkpoints (PD-1, CTLA-4), tumor EGFR pathway, VEGF-driven endothelial angiogenesis, and tumor DNA synthesis/replication.