AbbVie and Genmab are touting a much-anticipated first-line win for Epkinly as a combination treatment for diffuse large B-cell lymphoma (DLBCL), teeing up a potential change to the standard of care and fierce competition with Roche’s first-line Polivy regimen.
The drugmakers tested their bispecific antibody, also known as epcoritamab, in combination with the lymphoma standard of care rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine and prednisone (R-CHOP).
Together, Epkinly plus R-CHOP reduced the risk of disease progression or death by 51% in newly diagnosed patients with DLBCL compared with R-CHOP alone, according to topline results from the Epcore DLBCL-2 phase 3 trial. The study met its primary progression-free survival endpoint in patients with International Prognostic Index scores of 3 to 5, while the combination also reduced the risk of progression or death by 51% across the broader group of patients with IPI scores of 2 to 5.
AbbVie and Genmab said the combination was generally well tolerated and its safety profile was consistent with previously reported safety data for Epkinly and R-CHOP. Detailed results will be submitted for presentation at a future medical meeting.
"DLBCL is an aggressive disease and the need to advance treatment options is critical. These positive topline results suggest that epcoritamab combined with R-CHOP could offer a potential new standard of care in newly diagnosed DLBCL patients," said Daejin Abidoye, M.D., vice president and therapeutic area head of oncology, solid tumors and hematology at AbbVie.
The 51% drop in the risk of progression or death is “highly relevant to everyday practice. These results have the potential to be practice-changing," said Gilles Salles, M.D., Ph.D., chief of lymphoma service at Memorial Sloan Kettering. Salles was an investigator on both the Epcore DLBCL-2 trial and the landmark study that established R-CHOP as a standard of care nearly 25 years ago.
A bispecific antibody, Epkinly is given by subcutaneous injection and works by redirecting T cells to attack B cells in B-cell lymphoma. It’s currently approved under the FDA's accelerated approval pathway as a third-line therapy for DLBCL after patients have received at least two prior lines of systemic therapy. Epkinly, marketed as Tepkinly in Europe and some other markets, brought in $312 million in global sales during the first half of 2026 across its approved indications.
An estimated 25,000 cases of DLBCL are diagnosed each year in the U.S., representing a substantial market should the Epkinly-R-CHOP combination secure a first-line approval. TD Cowen analysts have said a positive first-line readout could give investors confidence that Epkinly can reach $3 billion in peak sales.
Such an approval would place Epkinly in a heated rivalry with Roche’s blockbuster Polivy, an infused antibody-drug conjugate approved in 2023 as part of a first-line combination with rituximab, cyclophosphamide, doxorubicin and prednisone, or R-CHP. In that regimen, Polivy takes the place of vincristine in R-CHOP. Polivy generated 808 million Swiss francs (about $972 million) in global sales in the first half of 2026.
The topline efficacy figures also set up a closely watched comparison with Polivy, though the results come from separate trials and cannot be directly compared. Epkinly plus R-CHOP posted a hazard ratio of 0.49 for disease progression or death in Epcore DLBCL-2. In Roche’s registrational Polarix study, Polivy plus R-CHP recorded a hazard ratio of 0.73, reflecting a 27% reduction in the risk of progression, relapse or death compared with R-CHOP.
The studies also differed somewhat in how their patient populations were analyzed. Epcore DLBCL-2 enrolled patients with IPI scores of 2 to 5, while its primary progression-free survival endpoint was assessed in patients with scores of 3 to 5. Polarix enrolled patients with IPI scores ranging from 2 to 5.
Roche’s Columvi, which works through the same CD20xCD3 bispecific mechanism as Epkinly, is also gunning for earlier placement in the DLBCL treatment lineup. Columvi is approved under the FDA's accelerated approval pathway for third-line or later DLBCL. But last year, the FDA rejected Roche’s bid for a second-line combination with GemOx, concluding that data from the phase 3 Starglo trial did not provide sufficient evidence to support the proposed indication in the U.S. patient population.
For AbbVie and Genmab, the latest readout is a welcome relief after a surprise phase 3 setback for Epkinly as a monotherapy in the Epcore DLBCL-1 trial earlier this year. While Epkinly improved progression-free survival, the study failed to show a statistically significant improvement in overall survival, which was the sole U.S. primary endpoint.
Hope rebounded in late June, when AbbVie and Genmab announced a positive phase 3 readout for Epkinly plus lenalidomide in patients with relapsed or refractory DLBCL who had received at least one prior line of treatment. The combination significantly improved progression-free survival compared with R-GemOx in the Epcore DLBCL-4 trial.
Neither the first-line Epkinly-R-CHOP regimen nor the Epkinly-lenalidomide regimen is approved for these uses. The drugmakers said they would work with global regulators to determine the next steps.