Phase 1b REBEL tests EBRT then epcoritamab/glofitamab CD20×CD3 T‑cell engagers in R/R DLBCL.

This Phase 1b, single-group, open-label study at University of Utah evaluates whether a short course of external beam radiation therapy (up to ~20 Gy, delivered over 5 days) can be safely followed immediately by a CD20×CD3 bispecific antibody—either epcoritamab (Genmab + AbbVie) or glofitamab/Columvi (Roche/Genentech). Both antibodies are T‑cell–redirecting agents that bind CD20 on malignant B cells and CD3 on T cells to drive tumor cell killing; the key feasibility question is whether “radiation priming” can improve local control and systemic immune activity without unacceptable cytokine release syndrome, neurotoxicity, or overlapping cytopenias/infections in heavily pretreated patients. Eligible patients have relapsed/refractory large B‑cell lymphoma (including DLBCL NOS and related entities) after at least two prior systemic regimens, with Lugano-measurable disease including at least one non-irradiated lesion for response assessment. In this 3rd-line+ setting, today’s care commonly includes CAR‑T for eligible patients, antibody-drug conjugates and other systemic options, or palliative radiation for symptomatic sites; this study explores a practical sequence that could pair a familiar local modality with off-the-shelf bispecific immunotherapy.