eligibility_summary
Eligible: metastatic or unresectable ESCC confirmed histologically/cytologically, progressed after 1 prior platinum-based line and prior PD‑1/PD‑L1 IO, tumor tissue available, prior AEs recovered to ≤Grade1 (endocrine AEs on replacement and ≤Grade2 neuropathy allowed). Exclude: aortic/tracheal invasion, >10% recent weight loss, severe ocular surface disease, IBD, recent investigational use, other active cancers, active CNS mets/meningitis, HIV with Kaposi’s/MCD, allogeneic transplant, recent serious CV disease, high GI‑bleed risk.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
NCT05319730 (KEYMAKER-U06 Substudy 06B) is a Phase 1/2 umbrella trial in 2L esophageal squamous cell carcinoma post–PD-1/PD-L1 therapy. Interventions and mechanisms: - Pembrolizumab: anti–PD-1 monoclonal antibody, restores T‑cell antitumor activity (immune checkpoint inhibitor). - MK‑4830: anti‑ILT4 (LILRB2) monoclonal antibody, reverses myeloid-derived immunosuppression (myeloid checkpoint inhibitor). - Lenvatinib: oral multi‑target tyrosine kinase inhibitor (VEGFR1‑3, FGFR1‑4, PDGFRα, RET, KIT), anti‑angiogenic and immunomodulatory. - Sacituzumab tirumotecan (SKB264/MK‑2870): TROP2‑directed antibody–drug conjugate delivering a topoisomerase I inhibitor to TROP2+ tumor cells. - Paclitaxel: cytotoxic microtubule stabilizer (mitotic arrest). - Irinotecan: cytotoxic topoisomerase I inhibitor (DNA damage). Targeted cells/pathways: PD‑1/PD‑L1 axis on T cells/tumor, ILT4 on tumor‑associated myeloid cells (TAMs/MDSCs), angiogenesis via VEGF/FGF signaling in tumor vasculature, TROP2 on ESCC cells, microtubules (β‑tubulin) and DNA replication via topo I.