Epcoritamab Phase 3 Data and Bispecific Antibody Differentiation in DLBCL

Dr. Graff reviews the EPCORE DLBCL-1 Phase 3 trial comparing epcoritamab monotherapy against investigator's choice of R-GemOx or bendamustine-rituximab in relapsed/refractory DLBCL. The trial demonstrated progression-free survival, complete response rate, and duration of response superiority for epcoritamab monotherapy, though overall survival was not statistically significantly different, partly because many control arm patients went on to receive subsequent active therapies including CAR-T.

She and Dr. Westin agree that R-GemOx has now been beaten by multiple novel agents across trials (glofitamab-GemOx, mosunetuzumab-polatuzumab vedotin, and epcoritamab) and is no longer an appropriate comparator arm going forward.

Dr. Lunning differentiates available bispecific agents using a chess metaphor of a rook, bishop, and knight each with specific moves and roles. Mosunetuzumab spans the broadest age range but requires a partner drug in DLBCL. Epcoritamab is subcutaneously administered continuously until progression or intolerance, with IgG level monitoring and liberal intravenous immunoglobulin use to manage infection risk throughout the treatment course. Glofitamab is fixed-duration therapy for patients achieving complete or partial response, typically paired with GemOx. Prior exposure to polatuzumab vedotin in earlier lines makes mosunetuzumab-polatuzumab combinations less attractive for patients already treated with Pola-R-CHP.

Dr. Johnson notes that cytokine release syndrome risk varies between agents, which may influence agent selection for patients perceived as less tolerant of high-grade cytokine release syndrome events.