Genmab and AbbVie’s bispecific antibody halves progression-or-death risk in lymphoma trial

Why it matters: The companies call EPCORE DLBCL-2 the first Phase 3 trial of a bispecific antibody combination to significantly improve progression-free survival (PFS) — how long patients live without their lymphoma worsening — in newly diagnosed DLBCL. A frontline label would move epcoritamab — authorized in the EU as monotherapy for relapsed or refractory DLBCL after two or more lines of systemic therapy — into a setting where Roche’s antibody-drug conjugate Polivy has been approved since 2022.

• “While treatment advances have improved outcomes for patients with diffuse large B-cell lymphoma, options for newly diagnosed patients remain limited, reinforcing the need for additional therapies that can treat as many patients as possible in the frontline setting,” said Genmab CEO Jan van de Winkel.

By the numbers:

• Among patients with International Prognostic Index (IPI) risk scores of 3 to 5 — the trial’s primary population — epcoritamab plus R-CHOP lowered the risk of progression or death by 51% versus R-CHOP alone (hazard ratio 0.49; 95% CI 0.35–0.69), the companies said.
• Across all patients, with IPI scores of 2 to 5, the hazard ratio was also 0.49 (95% CI 0.36–0.67).

Zoom in: Epcoritamab binds CD20 on B cells and CD3 on T cells, prompting the T cells to kill the B cells. In the trial, designed to randomize about 900 patients 2:1, it was given as a fixed course of injections under the skin.

The competition: Epcoritamab would enter a frontline field that has begun to move beyond R-CHOP.

• Roche’s Polivy is approved with R-CHP — R-CHOP without vincristine. In the 879-patient POLARIX trial behind that approval, 76.7% of patients on the Polivy regimen were alive without progression at two years, against 70.2% on R-CHOP.
• Incyte’s CD19 antibody tafasitamab, added with lenalidomide to R-CHOP, improved PFS in the 899-patient frontMIND trial; Incyte says the data support regulatory applications worldwide.
• Rival CD20×CD3 bispecifics are in frontline Phase 3 trials too: Roche’s SKYGLO adds glofitamab to Polivy’s regimen and compares the combination with that regimen, while Regeneron’s OLYMPIA-3 pits odronextamab plus CHOP, without rituximab, against R-CHOP.

Reality check: EPCORE DLBCL-2 tested the combination against R-CHOP, not against Polivy’s regimen, which 2025 European Hematology Association guidelines list alongside R-CHOP for advanced-stage disease with IPI scores of 2 to 5.

• The companies have released hazard ratios but no absolute PFS rates, overall-survival results or adverse-event rates from the trial, saying the combination was generally well tolerated. They will submit the data for presentation at a future medical meeting.

Backstory: Epcoritamab’s Phase 3 record in DLBCL is mixed. In January, the drug alone improved PFS in relapsed or refractory disease but did not significantly improve overall survival, the trial’s sole primary endpoint in the U.S. In June, a combination with lenalidomide significantly improved PFS in the same setting, European Biotechnology reported.

Market reaction: Genmab shares were up about 8% in Copenhagen in morning trading on Tuesday. On Monday, Phase 2 ovarian cancer data for rinatabart sesutecan (Rina-S), the centerpiece of Genmab’s $1.8 billion (€1.7 billion at the time) ProfoundBio takeover, had lifted them more than 4% in early trading.