eligibility_summary
Adults (≥18) with histologically confirmed MZL (splenic/nodal/extranodal), relapsed/refractory, ≥1 measurable lesion on CT/MRI, ECOG 0–2, and prior systemic therapy including ≥1 anti‑CD20 regimen (combo ≥2 cycles, monotherapy ≥4 doses, waived if progressed on treatment). Exclude recent anticancer therapy (<2 wks), investigational drug (<4 wks)/other trials, prior BTK inhibitor, R2‑refractory disease, or CNS/meningeal involvement.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 3, randomized, open-label trial in relapsed/refractory marginal zone lymphoma compares: 1) Orelabrutinib (oral small‑molecule, covalent Brutons tyrosine kinase [BTK] inhibitor) + rituximab vs 2) Lenalidomide (oral immunomodulatory drug, IMiD) + rituximab. Mechanisms: • Orelabrutinib blocks BTK in the B‑cell receptor (BCR) pathway, suppressing downstream NF‑κB/PI3K–AKT/MAPK signaling to inhibit proliferation/survival of malignant B cells. • Rituximab is an anti‑CD20 monoclonal IgG1 antibody that depletes CD20+ B cells via ADCC, CDC, and apoptosis. • Lenalidomide binds cereblon (CRBN) to degrade IKZF1/3, enhancing T‑cell and NK‑cell activation, boosting ADCC with rituximab, and exerting anti‑tumor/anti‑angiogenic effects. Targets: CD20+ marginal zone B cells, BTK/BCR signaling, immune effector cells via CRBN‑IKZF pathway.