Genmab and AbbVie's epcoritamab cuts lymphoma progression risk by 51% in frontline Phase 3

Genmab and AbbVie said on 5 October 2026 that adding their bispecific antibody epcoritamab to standard R-CHOP chemotherapy cut the risk of disease progression or death by 51% in newly diagnosed diffuse large B-cell lymphoma (DLBCL), in the Phase 3 EPCORE DLBCL-2 trial ¹. The companies will now engage global regulatory authorities ¹.

What the trial found

EPCORE DLBCL-2 is a global, open-label, multi-centre, randomised Phase 3 trial comparing fixed-duration, subcutaneous epcoritamab plus R-CHOP with R-CHOP alone ¹. It enrolled patients with an International Prognostic Index (IPI) score of 2 to 5, and BioPharma Dive reports that 900 people at intermediate or high risk took part ¹². Patients were randomised 2:1 to six cycles of epcoritamab plus R-CHOP followed by two cycles of epcoritamab alone, or six cycles of R-CHOP followed by two cycles of rituximab ¹.

The primary endpoint was progression-free survival (PFS) in patients with an IPI of 3 to 5. In that group the risk of progression or death fell by 51% (HR 0.49 [95% CI 0.35, 0.69]; p-value < 0.0001) ¹. The key secondary endpoint, PFS across all patients with an IPI of 2 to 5, showed the same 51% reduction (HR 0.49 [95% CI 0.36, 0.67]; p-value < 0.0001) ¹. The companies describe it as the first Phase 3 study of a bispecific antibody combination to show a statistically significant and clinically meaningful PFS improvement in frontline DLBCL ¹. They said the combination was generally well tolerated, with a safety profile consistent with that of epcoritamab and R-CHOP given separately ¹.

Daejin Abidoye, AbbVie's therapeutic area head for oncology, solid tumour and haematology, said the combination "could offer a potential new standard of care in newly diagnosed DLBCL patients" ³. Gilles Salles of Memorial Sloan Kettering Cancer Center, an investigator on the trial, said the results "have the potential to be practice-changing" ¹.

What it means for the market

DLBCL is the most common type of non-Hodgkin lymphoma, at approximately 25-30 percent of cases, with approximately 25,000 new diagnoses a year in the US ¹. Epcoritamab is sold as Epkinly in the US and Japan and Tepkinly in the EU, and is approved in certain lymphoma indications in more than 65 countries ¹. Genmab and AbbVie share commercial responsibilities in the US and Japan, and AbbVie leads commercialisation elsewhere ¹. Genmab reported $312 million in global net sales of the drug in the first half of the year, and its shares rose as much as 14% after the news ².

BioPharma Dive reports that the result exceeded investor expectations of around a 40% relative risk reduction and puts Epkinly on track to become the first drug of its kind approved in first-line DLBCL ². TD Cowen analyst Yaron Werber wrote that it "should become the undisputed" standard of care, with eventual sales of $3 billion a year, and Jefferies analyst Benjamin Jackson wrote that his firm's forecast of $1.4 billion in first-line peak sales "could prove conservative" ². Jackson cautioned that reaching those figures depends on the partners' ability to gain market share ².

Other competitors are in development. Roche's Lunsumio has completed a Phase 2 trial, and AstraZeneca's Calquence is in a Phase 3 trial in frontline disease with results expected early next year ². For hospitals, bispecifics carry immune-related side effects that have made them hard to deliver outside academic medical centres, as inpatient monitoring is sometimes recommended, although many providers now assess side effects remotely ².

Caveats

These are topline results only, and the announcement reports progression-free survival but no overall survival data ¹. Comparisons with Roche's Polivy, which BioPharma Dive says the data topped, cross trials and can mislead ². The combination is investigational and not approved by any regulator ¹. The trial began on 8 February 2023 and is ongoing, and the data will be submitted for presentation at a future medical meeting ¹.