Epcoritamab plus R-CHOP halves progression risk in first-line lymphoma trial

Overview

Updated 1 hour ago

AbbVie and Genmab said Monday that adding their bispecific antibody epcoritamab to the R-CHOP chemoimmunotherapy backbone cut the risk of disease progression or death by 51% in newly diagnosed diffuse large B-cell lymphoma (DLBCL). It is the first phase 3 trial of a bispecific antibody to beat R-CHOP in the frontline setting — a regimen that has anchored treatment for over 20 years.

The win positions epcoritamab against Roche's Polivy, approved for the same first-line indication in April 2023 after its own phase 3 success. But the topline carries no overall survival, complete response, or safety details yet, and epcoritamab's known risks — cytokine release syndrome, neurologic events, and step-up dosing that can require hospitalization — will shape whether community oncology centers adopt it.

Why it matters

If the data hold, this is the first frontline DLBCL regimen in 20 years to beat R-CHOP — and a test of bispecifics in community care.

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Key Indicators

51%

Reduction in risk of disease progression or death

Hazard ratio 0.49 for epcoritamab + R-CHOP versus R-CHOP alone.

0.49

Hazard ratio for progression-free survival

95% confidence interval 0.36–0.67, p-value less than 0.0001.

2–5

International Prognostic Index score of enrolled patients

Trial enrolled newly diagnosed DLBCL patients with IPI 2–5.

0.73

Hazard ratio from rival POLARIX trial (pola-R-CHP vs R-CHOP)

Benchmark win behind Roche's Polivy, in the same IPI 2–5 population.

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People Involved

Jan van de Winkel

Chief executive officer, Genmab

Leading Genmab's epcoritamab collaboration with AbbVie

Organizations Involved

AbbVie (Allergan)

Pharmaceutical company

Co-developer and co-commercializer of epcoritamab

American biopharmaceutical company spun off from Abbott Laboratories in 2013.

Genmab

Biotechnology company

Co-developer of epcoritamab

Danish antibody biotech, developer of the DuoBody platform used to make epcoritamab.

Roche / Genentech

Pharmaceutical company

Competitor; markets Polivy and runs a frontline glofitamab trial

Swiss pharma whose Polivy is the existing FDA-approved first-line DLBCL alternative to R-CHOP.

Incyte

Biopharmaceutical company

Competitor; Monjuvi (tafasitamab) in first-line DLBCL

American biopharma that reported a phase 3 win for Monjuvi plus R-CHOP in January 2026.

Timeline

August 2002 October 2026

7 events Latest: 3 days ago

Tap a bar to jump to that date

October 2026
Epcoritamab + R-CHOP cuts progression risk 51%
Latest Clinical trial

EPCORE DLBCL-2 interim analysis shows hazard ratio 0.49; IDMC recommends unblinding the study.
3 days ago
January 2026
Incyte reports Monjuvi phase 3 win
Clinical trial

Tafasitamab plus R-CHOP cuts first-line progression risk about 25%; US filing planned for H1 2026.
January 2026
May 2023
FDA approves Epkinly in relapsed DLBCL
Regulatory approval

Epcoritamab wins approval in relapsed/refractory DLBCL with CRS and neurologic warnings.
May 14th, 2023
April 2023
FDA approves Polivy for first-line DLBCL
Regulatory approval

Roche's pola-R-CHP becomes the first approved first-line regimen beyond R-CHOP.
April 19th, 2023
February 2023
EPCORE DLBCL-2 trial opens
Clinical trial

Randomizes newly diagnosed DLBCL patients with IPI 2–5 to epcoritamab + R-CHOP or R-CHOP alone.
February 8th, 2023
January 2022
POLARIX results published
Clinical trial

Polatuzumab vedotin plus R-CHP beats R-CHOP in first-line DLBCL, hazard ratio 0.73.
January 2022
August 2002
R-CHOP becomes the frontline standard
Clinical trial

GELA trial shows rituximab added to CHOP beats CHOP alone; R-CHOP anchors DLBCL treatment for 20 years.
August 2002

Scenarios

FDA approves epcoritamab plus R-CHOP for first-line DLBCL

Likely Resolves by Q2 2028

Discussed by: AbbVie and Genmab management; Truist analysts

AbbVie and Genmab said they will engage global regulators on next steps. If a filing follows and the FDA grants approval, epcoritamab becomes the first bispecific antibody approved in first-line DLBCL, joining Polivy as an alternative to R-CHOP. Adoption will hinge on full safety data: cytokine release syndrome rates, neurologic events, and whether the step-up dosing schedule works in community infusion centers.

ASH 2026 readout shows no OS gain; safety costs slow adoption

Uncertain Resolves by End of 2026

Discussed by: apoapenews treatment analysis; Medscape

The topline offers no overall survival, complete response, or adverse-event numbers. If the full presentation at the American Society of Hematology meeting in December 2026 shows no significant OS benefit and meaningful grade 3+ CRS or neurologic events requiring step-up dosing and hospitalization, community oncology uptake will lag. Polivy would keep the frontline lead despite its smaller hazard ratio, given its proven profile.

Roche's glofitamab trial reads positive, splitting the frontline market

Uncertain Resolves by End of 2027

Discussed by: apoapenews frontline-trial comparison

Roche's glofitamab plus pola-R-CHP trial (NCT06047080) enrolled 1,130 patients and is due at primary completion in October 2027. If it reports a positive PFS result, the first-line choice shifts from chemoimmunotherapy versus chemoimmunotherapy-plus-one to which bispecific on which backbone: glofitamab on the Polivy backbone or epcoritamab on R-CHOP.

Historical Context

3 moments from history that rhyme with this story — and how they unfolded.

August 2002

GELA LNH-98-5 trial — R-CHOP becomes the standard (2002)

The French GELA group randomized 399 previously untreated elderly DLBCL patients to CHOP chemotherapy alone or CHOP plus the anti-CD20 antibody rituximab. At five years, overall survival was 58% with R-CHOP versus 45% with CHOP, a decisive win published in the New England Journal of Medicine.

Then

R-CHOP became the frontline DLBCL backbone worldwide within a few years.

Now

It has held for over 20 years; every major first-line advance since, including Polivy, has been layered onto it.

Why this matters now

Epcoritamab aims to replicate the rituximab step-change — an immune-targeting agent that materially beats R-CHOP — for the first time since 2002.

January 2022 – April 2023

POLARIX trial — Polivy wins the first frontline DLBCL approval (2022–2023)

POLARIX randomized 879 previously untreated DLBCL patients with an IPI of 2–5 to polatuzumab vedotin plus R-CHP (vincristine dropped) or R-CHOP. At 28.2 months median follow-up, two-year PFS was 76.7% versus 70.2%, a hazard ratio of 0.73. The FDA approved the regimen in April 2023 while documenting peripheral neuropathy and no overall-survival or complete-response difference.

Then

pola-R-CHP became the first FDA-approved first-line regimen beyond R-CHOP.

Now

It set the approval benchmark and the IPI 2–5 patient population that EPCORE DLBCL-2 now mirrors.

Why this matters now

EPCORE's hazard ratio of 0.49 looks larger than POLARIX's 0.73, but the trials differ: POLARIX was blinded and placebo-controlled, EPCORE is open-label with no absolute PFS, OS, or safety figures yet published.

May 2023

Epkinly (epcoritamab) first approval (2023)

The FDA approved epcoritamab in May 2023 for relapsed/refractory DLBCL after two or more prior lines, based on an open-label trial showing durable complete responses around 40%. The label warns of cytokine release syndrome and life-threatening neurologic problems, mandates step-up dosing, and states DLBCL patients may need hospitalization after the first full dose on day 15 of cycle 1.

Then

Epkinly established the bispecific as viable in later-line DLBCL.

Now

Its safety framework — CRS monitoring, step-up dosing, hospitalization — is the template any first-line use must answer to.

Why this matters now

The same safety requirements now apply in the frontline setting, where patients are fitter and typically treated in community infusion centers rather than specialized referral hospitals.