eligibility_summary
Adults 18–75 with inoperable/recurrent metastatic colorectal cancer (AJCC IV), measurable disease, RAS/BRAF WT, PD‑L1 CPS≥1 or TPS≥1% or CD8+ TILs≥2%, ECOG 0–1, life expectancy >3 mo, and adequate marrow/renal/hepatic/coagulation/thyroid function. No prior systemic therapy (adjuvant ≥6 mo allowed). Exclude prior anti‑EGFR/checkpoint therapy, active autoimmune/immunosuppression, major cardiac/ILD/infections (HBV/HCV/TB), recent cancer, live vaccine, pregnancy (use contraception), malabsorption, uncontrolled effusions, HIV, serious comorbidities.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 1b/2 single-arm trial in first-line RAS/BRAF wild-type metastatic colorectal cancer testing sintilimab + cetuximab + chemotherapy (mFOLFOX6, FOLFIRI, CAPEOX, or CAPIRI). Drugs/mechanisms: • Sintilimab: anti–PD-1 IgG4 monoclonal antibody, blocks PD-1 on T cells to reverse exhaustion and restore cytotoxic function. • Cetuximab: anti-EGFR chimeric IgG1 monoclonal antibody, inhibits EGFR signaling (MAPK/PI3K) and mediates ADCC via Fcγ receptors, enhancing immune cell killing. • Chemotherapy: fluoropyrimidines (5-FU/capecitabine, thymidylate synthase inhibition), oxaliplatin (DNA crosslinking), irinotecan (topoisomerase I inhibition) to cause tumor death and antigen release. Targeted cells/pathways: PD-1/PD-L1 checkpoint on CD8+ TILs, EGFR on tumor cells (in RAS/BRAF WT), NK cells and macrophages (FcγR-driven ADCC), with the combination aiming to increase TIL infiltration and convert “cold” to “hot” tumors.