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Epcoritamab with or without lenalidomide for elderly patients with Diffuse Large B-Cell Lymphoma

Efficacy and Safety of Epcoritamab Monotherapy and in Combination With Lenalidomide as First-line Therapy for Anthracycline-ineligible Diffuse Large B-Cell Lymphoma Patients, an Open-label, Randomized, Multicenter, Global Phase 2 Trial

PHASE2 · Genmab · NCT05660967

This study is testing if a new treatment called epcoritamab, alone or with another drug called lenalidomide, can help older patients with Diffuse Large B-Cell Lymphoma who can’t take standard chemotherapy.

Quick facts

PhasePHASE2
Study typeInterventional
Enrollment180 (estimated)
Ages75 Years and up
SexAll
SponsorGenmab (industry)
Drugs / interventionsepcoritamab, CAR-T, chemotherapy
Locations78 sites (Waukesha, Wisconsin and 77 other locations)
Trial IDNCT05660967 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of epcoritamab, both as a standalone treatment and in combination with lenalidomide, for elderly patients newly diagnosed with Diffuse Large B-Cell Lymphoma (DLBCL) who cannot tolerate anthracycline therapy. The trial is open-label and multicenter, designed in two stages: a safety run-in phase followed by an expansion of the selected treatment. Participants will receive either epcoritamab alone or epcoritamab plus lenalidomide, with all patients receiving active treatment. The study aims to provide a viable treatment option for those ineligible for traditional chemotherapy.

Who should consider this trial

Good fit: Ideal candidates are elderly patients aged 75 years or older with newly diagnosed CD20+ large cell lymphoma who are ineligible for anthracycline-based therapy.

Not a fit: Patients with active, clinically significant infections or those who do not meet the eligibility criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a safer and effective therapy option for elderly patients with DLBCL who cannot tolerate standard chemotherapy.

How similar studies have performed: Previous studies have shown promise with epcoritamab, but this specific combination approach is novel and has not been extensively tested.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Must have newly diagnosed CD20+ large cell lymphoma.
* Is ineligible for anthracycline-based therapy/cytotoxic chemotherapy due to:

  * Being age ≥80 years; AND/OR
  * Being age ≥75 years and having important comorbid condition(s), which are likely to have a negative impact on tolerability of anthracycline-based therapy/cytotoxic chemotherapy.
* Have Immune Effector Cell-Associated Encephalopathy (ICE) score of at least 8 out of 10.
* Have Ann Arbor Stage II-IV disease.
* Have ECOG PS of 0, 1, or 2; (ECOG PS of 3 may be considered if impairment is attributed to current lymphoma/DLBCL and if pre-phase treatment during the screening phase results in an improvement of ECOG PS to ≤2 prior to enrollment).
* Have measurable disease as per Lugano criteria.
* Have acceptable organ function based on baseline bloodwork.
* Must have fresh (preferred) or archival biopsy material at screening.

Exclusion Criteria:

* Has known active, clinically significant bacterial, viral, fungal, mycobacterial, parasitic, or other infection at trial enrollment, including COVID-19 infection.
* Has severe cardiovascular disease (other than those eligibility criteria that preclude the subject from receiving anthracycline-based therapy/cytotoxic chemotherapy),
* Has been exposed to/received any of the following prior therapies, treatments, or procedures within the specified timeframes:

  * Major surgery within 4 weeks prior to the first dose of epcoritamab;
  * Non-investigational antineoplastic agents (except anti-CD20 monoclonal antibodies) or any investigational drug within 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of epcoritamab;
  * Autologous hematopoietic stem cell transplantation (HSCT), CAR-T, allogeneic stem cell transplantation, or solid organ transplantation;
  * Live, attenuated vaccines within 30 days prior to initiation of epcoritamab;
  * Investigational vaccines within 28 days before the planned first dose of epcoritamab (ie, experimental and/or non-authorized SARS-CoV-2 vaccinations and therapies are not allowed);
  * Invasive investigational medical device use within 28 days before the planned first dose of epcoritamab.
* Has primary central nervous system (CNS) tumor or known CNS involvement or intracranial involvement as confirmed by mandatory brain magnetic resonance imaging/computed tomography (MRI/CT) scan at screening and, if clinically indicated, by lumbar puncture.
* Has a seizure disorder requiring anti-epileptic therapy or experienced a seizure within 6 months of signing an informed consent form.
* Has known past or current malignancy other than inclusion diagnosis, with exceptions as stated in protocol.
* Has known or suspected allergies, hypersensitivity, or intolerance to either of the trial treatments or has known or suspected contraindication to the use of all locally available anti-cytokine therapies per local guidelines for management of cytokine release syndrome (CRS).
* Has active hepatitis B virus (HBV) (DNA polymerase chain reaction \[PCR\]-positive) or hepatitis C virus (HCV) (RNA PCR-positive) infection, current alcohol abuse, or cirrhosis.
* Has active cytomegalovirus (CMV) infection (DNA PCR-positive) requiring treatment.
* Has suspected active or inadequately treated latent tuberculosis.
* Has a known history of seropositivity for HIV. Note: HIV testing is required at screening only if required per local health authorities or institutional standards.

Note: Other protocol defined inclusion/exclusion criteria may apply.

Where this trial is running

Waukesha, Wisconsin and 77 other locations

+28 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Diffuse Large B-Cell Lymphoma, Double-hit lymphoma, Triple-hit lymphoma, Follicular grade 3B, T-cell/histiocyte rich LBCL, DuoBody®, Anti-CD3, Anti-CD20

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.