eligibility_summary
Adults ≥18 with relapsed/refractory LBCL (incl FL3B, transformed, or HGBCL), COO by Hans, 1–5 prior regimens, Zubrod 0–3, baseline imaging within 28 days (PET‑CT preferred, PET‑CT required at EOT), measurable disease, adequate labs/organ function (ANC ≥1.0k/µL, Plt ≥75k/µL, CrCl ≥30 mL/min, hepatic per limits), controlled HIV/HBV/HCV, NYHA ≤2B, able to take oral meds, consent. Exclude CNS lymphoma, MDS/MPN markers, T‑LBL/ALL, ASCT candidates, prior tafasitamab/lenalidomide/BTKi/tazemetostat, allergies, interacting anticoagulants/CYP3A drugs, pregnancy, interfering malignancy.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
NCT05890352 tests adding targeted agents to tafasitamab-lenalidomide in relapsed/refractory large B‑cell lymphoma. Drugs and mechanisms: • Tafasitamab: anti-CD19 IgG1 monoclonal antibody (Fc‑enhanced) inducing ADCC/ADCP and apoptosis of CD19+ B cells. • Lenalidomide: immunomodulatory agent (IMiD) binding cereblon to degrade Ikaros/Aiolos, enhancing T/NK activity, with direct tumor/anti-angiogenic effects. • Tazemetostat: oral small‑molecule EZH2 (PRC2) inhibitor, lowering H3K27me3 and reactivating tumor suppressor genes, particularly relevant in GCB/EZH2‑mutant/EZB subtypes. • Zanubrutinib: oral covalent BTK inhibitor, blocking B‑cell receptor signaling and NF‑κB survival pathways. Targets: malignant CD19+ B cells, pathways include BCR/BTK→NF‑κB, epigenetic EZH2/PRC2, and immune effector functions boosted by IMiD + anti‑CD19 synergy.