Epcoritamab plus R-CHOP significantly improves progression free survival in newly diagnosed diffuse large B-cell lymphoma

AbbVie and Genmab have reported positive topline results from the Phase 3 EPCORE DLBCL-2 trial, which tested a fixed duration course of epcoritamab, a subcutaneously delivered T-cell engaging bispecific antibody, added to the standard R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine and prednisone). The comparison was against R-CHOP alone in newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) who had an International Prognostic Index score of 2 to 5.

Adding epcoritamab lowered the risk of disease progression or death by 51 per cent (HR 0.49; 95% CI 0.36 to 0.67; p<0.0001), a statistically significant and clinically meaningful gain in progression free survival. This is the first Phase 3 trial of a bispecific antibody combination to show such a benefit in patients newly diagnosed with DLBCL. Epcoritamab given alongside R-CHOP was generally well tolerated, and its safety profile matched what has been reported before for epcoritamab and R-CHOP individually.

The result came from the first planned interim efficacy analysis. Because the benefit was so clear, the Independent Data Monitoring Committee advised that the study be unblinded.

Daejin Abidoye, MD, vice president and therapeutic area head for oncology, solid tumour and haematology at AbbVie, said DLBCL is an aggressive disease and that better treatment options are urgently needed. He said the findings suggest epcoritamab with R-CHOP could become a new standard of care for newly diagnosed patients, and that they add to the company’s understanding of what bispecifics can do across lymphoma as it works to meet pressing needs in this group.

Jan van de Winkel, Ph.D., chief executive officer of Genmab, said the topline results could reshape the frontline treatment landscape, as no other Phase 3 study of a bispecific antibody combination has shown a significant progression free survival improvement in newly diagnosed DLBCL. He said that although treatment advances have improved outcomes in DLBCL, options for people newly diagnosed remain limited, which underlines the need for further therapies that can help as many frontline patients as possible.

Gilles Salles, MD, PhD, chief of the Lymphoma Service and holder of the Steven A. Greenberg Chair at Memorial Sloan Kettering Cancer Center, said he had worked on both the landmark trial that made R-CHOP a standard of care almost 25 years ago and on EPCORE DLBCL-2, so seeing the potential of bispecific antibody therapy in newly diagnosed DLBCL was especially meaningful to him. He called the 51 per cent reduction in the risk of progression or death clinically meaningful and highly relevant to everyday practice, and said the results could change practice and bring the chance of cure to more patients.

DLBCL is the most common type of non-Hodgkin lymphoma worldwide, making up roughly 25 to 30 per cent of all cases.

Epcoritamab plus R-CHOP is an investigational combination that has not been approved by any regulatory authority. AbbVie and Genmab will talk to regulators around the world to decide on next steps, and the data will be submitted for presentation at a future medical meeting.

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Related Topics and Keywords

DIFFUSE LARGE B-CELL LYMPHOMA, epcoritamab, large b cell lymphoma, lymphoma, R-CHOP