eligibility_summary
Adults ≥18 with newly diagnosed primary CNS DLBCL confirmed by brain/CSF/vitreous, no systemic disease or prior PCNSL therapy, ECOG ≤2, adequate organs, HIV−, negative pregnancy test, contraception required. Exclude: MRI-ineligible, isolated ocular disease, active autoimmune disease, live vaccine <30d, other malignancy, pneumonitis, HBV/HCV/TB, GI absorption issues, prohibited meds (CYP3A4/5, EIAEDs), immunosuppression, prior allo-SCT, effusions/edema, psychiatric, pregnancy/breastfeeding.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Pilot, open-label Phase 1 study in newly diagnosed primary CNS diffuse large B‑cell lymphoma testing pembrolizumab with chemoimmunotherapy. Interventions and mechanisms: pembrolizumab (humanized IgG4 monoclonal antibody, PD‑1 checkpoint inhibitor) to restore T‑cell activation, rituximab (anti‑CD20 monoclonal antibody) to deplete malignant B cells via ADCC/CDC/apoptosis, methotrexate (antimetabolite antifolate, inhibits DHFR → blocks thymidine/purine synthesis, S‑phase cytotoxic), temozolomide (oral alkylating agent, O6‑guanine DNA methylation → DNA damage/apoptosis). Targets/pathways: PD‑1/PD‑L1 axis on T cells in the CNS lymphoma microenvironment, CD20 on B‑cell lymphoma cells, folate/nucleotide synthesis pathways and DNA integrity in rapidly dividing lymphoma cells. Pembrolizumab is given during induction and as consolidation to enhance antitumor immunity.