eligibility_summary
Include: consent, ECOG ≤1, KRAS mutation or KRAS WT amplification (copy ≥8) via tissue or liquid biopsy, tumor tissue available, ≥1 measurable lesion (RECIST 1.1), adequate organ function, contraception (women >7 d after BGB-53038, >120 d after tislelizumab, >2 mo after cetuximab, men during and ≥4 mo after). Exclude: KRAS G12R, prior anti‑RAS therapy, active LM or uncontrolled brain mets (treated/stable allowed), other cancer <2 y, active HBV/HCV, significant infection ≤14 d.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Study tests BGB-53038, an oral small-molecule pan-KRAS inhibitor, as monotherapy and combined with tislelizumab (anti–PD-1 IgG4 monoclonal antibody) or cetuximab (anti-EGFR IgG1 monoclonal antibody) in advanced solid tumors with KRAS mutations or KRAS wild-type amplification. Mechanisms: BGB-53038 directly inhibits KRAS (multiple mutant alleles and amplified WT), aiming to block downstream RAS signaling (RAF–MEK–ERK/MAPK and PI3K–AKT) in tumor cells. Cetuximab blocks upstream EGFR receptor signaling to prevent RAS-pathway reactivation/bypass. Tislelizumab inhibits PD-1 on T cells to relieve immune checkpoint suppression and enhance antitumor T-cell activity. Targets: KRAS-driven tumor cells, EGFR-expressing tumor cells (notably CRC), and PD-1 on tumor-infiltrating T cells within the tumor microenvironment. Phase 1a/1b dose escalation/expansion.