eligibility_summary
Adults ≥18 with unresectable/metastatic pancreatic adenocarcinoma, measurable disease, ECOG 0–1. Progression after prior therapy (C1:any, C2:5‑FU). Adequate organ function, recovered from prior therapy, contraception. Exclude non‑adenocarcinoma, obstruction, prior PD‑(L)1, immunosuppression/autoimmune disease, pneumonitis/ILD, serious cardiac disease, active CNS mets, pregnancy, recent live vaccine, active infection, other active malignancy. HBV/HCV/HIV allowed if controlled.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Interventions: AGEN1423 (IV anti-CD73/TGFβ-trap bifunctional monoclonal antibody) plus botensilimab (IV Fc‑engineered anti‑CTLA‑4 monoclonal antibody), with or without gemcitabine (antimetabolite nucleoside analog) and nab‑paclitaxel (albumin‑bound microtubule stabilizer). Mechanisms: AGEN1423 inhibits CD73 (ecto‑5′‑nucleotidase) to reduce immunosuppressive adenosine and traps/neutralizes TGF‑β to relieve stromal fibrosis and T‑cell exclusion, botensilimab blocks CTLA‑4 to enhance T‑cell priming/activation and, via enhanced FcγR engagement, can deplete intratumoral Tregs. Targets/pathways: CD73–adenosine axis on tumor/immune cells, TGF‑β signaling in CAFs/Tregs, and CTLA‑4 on T cells, chemotherapy kills proliferating PDAC cells and can increase antigen release.