Epkinly (epcoritamab-bysp)

P3, N=72, Active, not recruiting, Genmab

P2, N=33, Not yet recruiting, City of Hope Medical Center

Currently, approximately sixty percent of patients are cured with R-CHOP as frontline treatment, while the remaining patients experience primary refractory or relapsed (R/R) disease. Recently, the introduction of Pola-R-CHP as front-line therapy has represented a major advance in the management of DLBCL, resulting in improved outcomes...The most extensively studied BsAbs, in both the frontline and relapsed/refractory (R/R) settings, include epcoritamab, glofitamab, mosunetuzumab, and odronextamab...EMA has also approved glofitamab in combination with gemcitabine and oxaliplatin (GemOx) for patients with R/R DLBCL ineligible for ASCT, whereas this indication has not been approved by FDA...BsAbs represent a breakthrough therapy in the treatment of DLBCL, especially in R/R diseases. The purpose of this article is to review the landscape of BsAbs in DLBCL.

We comprehensively evaluate FDA-approved targeted agents, including monoclonal antibodies (rituximab, brentuximab vedotin, obinutuzumab, mogamulizumab), immune checkpoint inhibitors (nivolumab, pembrolizumab), CAR T-cell therapies (axi-cel, tisa-cel, liso-cel, brexu-cel), bispecific T-cell engagers (mosunetuzumab, epcoritamab), and small-molecule inhibitors (ibrutinib, idelalisib, venetoclax). In conclusion, understanding the molecular basis of lymphoma and resistance mechanisms is critical to optimizing targeted therapy. This review synthesizes current evidence to inform clinical decision-making and outlines future directions for durable, personalized lymphoma care.

P2, N=30, Recruiting, Massachusetts General Hospital | Not yet recruiting --> Recruiting

P1, N=26, Recruiting, Memorial Sloan Kettering Cancer Center | Not yet recruiting --> Recruiting

Traditional chemoimmunotherapy (e.g., R-CHOP) yields complete response rates around 20-30% and median overall survival of 6-12 months; intensified regimens (R-EPOCH, hyper-CVAD) offer only modest gains...Bispecific antibodies (e.g., CD3×CD20 agents epcoritamab and mosunetuzumab) show promising activity and tolerable toxicity in relapsed/refractory RT. Ongoing trials are exploring combinations with checkpoint inhibitors, triplet regimens, and novel targets such as ROR1, CD47, and CDK9. Continued research into optimized induction, consolidation, and innovative immunotherapies is essential to improve outcomes in this biologically distinct, high-risk CLL-related lymphoma.

This case highlights the potential of epcoritamab combined with debulking therapy for treating CAR-T-refractory CD19-negative DLBCL. This is the first validated case in Japan showing that epcoritamab is a viable and safe treatment option for post-CAR-T relapse, addressing a critical unmet need in the current therapeutic landscape.

We evaluated fixed-duration epcoritamab with rituximab plus lenalidomide (R2) in R/R FL in arm 2 of EPCORE® NHL-2 (phase 1b/2; NCT04663347). CRS events were mostly low grade (38% G1, 11% G2, 2% G3), all resolved, and none led to epcoritamab discontinuation. Fixed-duration epcoritamab plus R2 demonstrated deep, durable responses with manageable safety and favorable outcomes in R/R FL, irrespective of risk features.

This study aimed to investigate the efficacy of CD20×CD3 BsAbs (mosunetuzumab, glofitamab, odronextamab, and epcoritamab) in patients with LBCL who experienced relapse or refractory disease following CAR-T therapy. To validate these findings and determine the optimal sequencing of BsAbs and CAR-T therapy for R/R LBCL patients, prolonged follow-up periods and further prospective clinical trials are warranted. https://www.crd.york.ac.uk/prospero/, identifier CRD42024621005.

P3, N=116, Not yet recruiting, Australasian Leukaemia and Lymphoma Group

Novel therapies have significantly improved DLBCL outcomes, however challenges remain, including treatment toxicity, accessibility, and variability in patients' response. Future research should aim to optimize combination therapies, identify biomarkers predictive of response, and enhance toxicity management to improve patient care.