Phase 2 epcoritamab CD20×CD3 bispecific antibody plus R-CHOP in newly diagnosed aggressive B-cell NHL

This Phase 2, open-label, two-arm, sequential-assignment study tests epcoritamab (a subcutaneous CD20×CD3 T-cell–engaging bispecific antibody) combined with R-CHOP in newly diagnosed, CD20+ aggressive B-cell non-Hodgkin lymphoma, with the key comparison being two dexamethasone prophylaxis approaches in cycle 2 to manage cytokine release syndrome (CRS). R-CHOP includes rituximab (CD20 monoclonal antibody; originally from Genentech/Roche), cyclophosphamide (alkylator), doxorubicin/hydroxydaunorubicin (topoisomerase II inhibitor anthracycline), vincristine/oncovin (microtubule inhibitor), and prednisone/prednisolone (glucocorticoid). Eligible histologies include de novo or transformed DLBCL, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double-/triple-hit; a small subset of DLBCL, commonly ~5–10%), PMBCL, T-cell/histiocyte-rich LBCL, EBV+ DLBCL, and follicular lymphoma grade 3b. The scientific/commercial angle is moving AbbVie and Genmab’s epcoritamab (EPKINLY) earlier into front-line chemoimmunotherapy to potentially deepen complete responses while proactively optimizing CRS mitigation to make outpatient delivery practical. Today’s care for most newly diagnosed aggressive CD20+ B-cell lymphomas is R-CHOP (or intensified regimens for select high-risk biology) with response assessment by PET/CT; patients not cured proceed to salvage chemo and/or CAR T-cell therapy depending on fitness and access, and this study explores whether adding a CD20×CD3 engager up front can improve depth and durability of remission beyond chemoimmunotherapy alone.