Subcutaneous Epcoritamab With or Without Lenalidomide as First Line Therapy for Diffuse Large B-Cell Lymphoma (EPCORE DLBCL-3)

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

The purpose of the study is to examine efficacy and safety of epcoritamab with and without lenalidomide in newly diagnosed elderly patients with Diffuse Large B-Cell Lymphoma (DLBCL) who cannot tolerate anthracycline therapy. Epcoritamab (also known as EPKINLY™, GEN3013 and DuoBody®-CD3xCD20) is an antibody that has already been tested in several clinical studies. All patients will receive active treatment. There is an equal chance of receiving epcoritamab or epcoritamab plus lenalidomide.

Study Overview

• Status: Active, not recruiting
• Conditions: Diffuse Large B-Cell Lymphoma
• Intervention / Treatment: Biological: Epcoritamab; Drug: Lenalidomide

Detailed Description

This is an open-label, multicenter, global phase-2 trial evaluating the efficacy and safety of epcoritamab monotherapy and epcoritamab plus lenalidomide in elderly patients who are deemed anthracycline ineligible.

The trial is designed in two stages:

• Stage 1 which includes a safety run-in phase in each arm
• Stage 2, an expansion of the selected treatment from Stage 1

• Study Type: Interventional
• Enrollment (Actual): 111
• Phase: Phase 2

Expanded Access

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Contacts and Locations

Study Locations

• Austria
  • Linz, Austria
    • Kepler Universitätsklinikum
  • Salzburg, Austria
    • LKH - Universitätsklinikum der PMU Salzburg
  • Wels, Austria
    • Klinikum Wels-Grieskirchen GmbH
• Belgium
  • Anderlecht, Belgium
    • Institut Jules Bordet
  • Antwerp, Belgium
    • ZNA
  • Jette, Belgium
    • UZ Brussels
  • Leuven, Belgium
    • UZ Leuven
  • Roeselare, Belgium
    • AZ Delta
  • Temse, Belgium
    • Vitaz
  • Turnhout, Belgium
    • AZ Turnhout - Campus Sint-Elisabeth
• Czechia
  • Hradec Králové, Czechia
    • Fakultni Nemocnice Hradec Kralove
  • Prague, Czechia
    • Fakultni nemocnice v Motole
  • Prague, Czechia
    • Vseobecna fakultni nemocnice v Praze
• France
  • Angers, France
    • Chu Angers - Hôpital Hôtel Dieu
  • Créteil, France
    • Hôpital Henri Mondor
  • Lille, France
    • Hopital Claude Huriez - CHRU Lille
  • Marseille, France
    • Hopital de la Conception - APHM
  • Nantes, France
    • CHU de Nantes - Hotel Dieu
  • Paris, France
    • Hôpital Saint-Antoine
  • Paris, France
    • Hôpital Saint-Louis
  • Pessac, France
    • CHU de Bordeaux - Hopital Haut-Leveque
  • Salouël, France
    • CHU Amiens - Hopital Sud
  • Tours, France
    • CHU Tours - Hôpital BRETONNEAU
• Germany
  • Aachen, Germany
    • Universitaetsklinikum Aachen AoeR
  • Berlin, Germany
    • Vivantes Klinikum Neukoelln
  • Würzburg, Germany
    • Universitaetsklinikum Wuerzburg
  • Baden-Wurttemberg
    • Freiburg im Breisgau, Baden-Wurttemberg, Germany
      • Universitaetsklinikum Freiburg
• Italy
  • Ancona, Italy
    • Clinica di Ematologia AOU Ospedali Riuniti di Ancona
  • Aviano, Italy
    • IRCCS Centro di Riferimento Oncologico
  • Bologna, Italy
    • Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS
  • Brescia, Italy
    • Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
  • Candiolo, Italy
    • Fondazione del Piemonte per l'Oncologia IRCC Candiolo
  • Meldola, Italy
    • IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori "Dino Amadori" - IRST
  • Milan, Italy
    • Ospedale San Raffaele
  • Milan, Italy
    • IEO Istituto Europeo di Oncologia Parent
  • Palermo, Italy
    • Azienda Ospedaliera Vincenzo Cervello
  • Piacenza, Italy
    • AUSL Piacenza Ospedale Guglielmo da Saliceto
  • Trieste, Italy
    • Azienda sanitaria integrata università di Trieste
• Japan
  • Fukuoka, Japan
    • Kyushu University Hospital
  • Kagoshima, Japan
    • Kagoshima University Hospital
  • Kanazawa, Japan
    • Kanazawa University Hospital
  • Kashiwa, Japan
    • National Cancer Center Hospital East
  • Kōtoku, Japan
    • Cancer Institute Hospital of Jfcr
  • Matsuyama, Japan
    • Matsuyama Red Cross Hospital
  • Nagoya, Japan
    • NHO Nagoya Medical Center
  • Yamagata, Japan
    • Yamagata University Hospital
  • Ōsaka-sayama, Japan
    • Kindai University Hospital
• Poland
  • Biała Podlaska, Poland
    • Wojewodzki Szpital Specjalistyczny w Bialej Podlaskiej
  • Krakow, Poland
    • Pratia McM Krakow
  • Skorzewo, Poland
    • Centrum Medyczne Pratia Poznan
  • Torun, Poland
    • MICS Centrum Medyczne Torun
• South Korea
  • Daegu, South Korea
    • Keimyung University Dongsan Hospital
  • Goyang-si, South Korea
    • National Cancer Center
  • Jeonju, South Korea
    • Jeonbuk National University Hospital
  • Seoul, South Korea
    • Asan Medical Center
  • Seoul, South Korea
    • Samsung Medical Center
  • Seoul, South Korea
    • Seoul National University Hospital
• Spain
  • Badalona, Spain
    • Ico Badalona - Hospital Universitari Germans Trias I Pujol
  • Barcelona, Spain
    • Hospital Clínic de Barcelona
  • Barcelona, Spain
    • ICO l'Hospitalet - Hospital Duran i Reynals
  • Cáceres, Spain
    • Hospital San Pedro De Alcantara
  • Madrid, Spain
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain
    • Hospital Universitario Ramon Y Cajal
  • Madrid, Spain
    • Hospital Universitario Fundacion Jimenez Diaz
  • Seville, Spain
    • Hospital Universitario Virgen Macarena
  • Seville, Spain
    • Hospital Universitario Nuestra Señora de Valme
  • Seville, Spain
    • Hospital Universitario Puerta Del Mar
• United Kingdom
  • London, United Kingdom
    • Royal Marsden Hospital - Fulham
  • Plymouth, United Kingdom
    • Derriford Hospital
  • Southampton, United Kingdom
    • Southampton General Hospital
  • Sutton, United Kingdom
    • Royal Marsden Hospital
  • Truro, United Kingdom
    • Royal Cornwall Hospital NHS Trust
• United States
  • Wisconsin
    • Waukesha, Wisconsin, United States, 53188
      • UW Cancer Center at ProHealth Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 75 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Epcoritamab monotherapy	Biological: Epcoritamab; Epcoritamab will be administered by subcutaneous (SC) injections in 28-day cycles for up to 12 cycles.; Other Names: GEN3013; DuoBody®-CD3×CD20; EPKINLY™
Experimental: Epcoritamab in combination with lenalidomide	Biological: Epcoritamab; Epcoritamab will be administered by subcutaneous (SC) injections in 28-day cycles for up to 12 cycles.; Other Names: GEN3013; DuoBody®-CD3×CD20; EPKINLY™; Drug: Lenalidomide; Lenalidomide will be administered orally (capsules; starting dose of 10 or 20 mg) once daily on Day 1 to Day 21 of each 28-day cycle for up to 12 cycles.; Other Names: Revlimid®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response (CR) rate	Percentage of participants achieving CR. Assessed by the Investigator per Lugano criteria	From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DOR)	Defined as the time between date of first response to the date of first documented tumor progression or death (due to any cause) whichever occurs first	From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years
Duration of complete response (DOCR)	Defined as the time between the date of first CR to the date of the first documented tumor progression or death due to any cause, whichever comes first	From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years
Time to response (TTR)	Defined as the time from first dose to first documentation of objective tumor response (CR or PR)	From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 1 year
Overall Response Rate (ORR)	Defined as the percentage of patients who achieve best overall response of complete response (CR) or partial response (PR) determined by Lugano criteria	From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years
Progression-free survival (PFS)	Defined as the time from first dose to date of PD or death (due to any cause) whichever occurs first	From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years
Time to next anti-lymphoma therapy (TTNT)	Defined as the time from first dose to administration of subsequent anti-lymphoma therapy	From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years
Rate of minimal residual disease (MRD) negativity	Percentage of participants with at least 1 post-screening MRD negative result	From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years
Overall survival (OS)	Defined at the timeframe from first dose to death	From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 3 years
Incidence and severity of adverse events (AEs)	An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment	From screening until end of the safety follow-up period (60 days after last dose)
Incidence of clinically significant shifts in laboratory parameters	Clinical laboratory parameters assessed: hematology, chemistry, coagulation, tumor lysis, cardiac enzymes, immunoglobulins, and urinalyses	From screening until end of the safety follow-up period (60 days after last dose)
Incidence of anti-drug antibodies (ADAs) to epcoritamab in plasma	To evaluate immunogenicity	From first dose until treatment discontinuation (assessed up to 12 months)
Evaluate patient-reported outcomes (PROs) related to lymphoma symptoms	Changes in lymphoma symptoms as measured by the Functional Assessment of Cancer Therapy Lymphoma (FACT-Lym). Scale from 0-168 obtained by summing individual subscale scores. Higher scores for the scales indicate better quality of life	From cycle 1, day 1 until 90 days after last dose (each cycle is 28 days)
Assess pharmacokinetics (PK) of epcoritamab	Total body clearance of drug from the plasma (CL)	From first dose and at multiple time points until treatment discontinuation (assessed up to 12 months)
Assess pharmacokinetics (PK) of epcoritamab	Maximum observed concentration (Cmax)	From first dose and at multiple time points until treatment discontinuation (assessed up to 12 months)
Assess pharmacokinetics (PK) of epcoritamab	Time to reach Cmax (Tmax)	From first dose and at multiple time points until treatment discontinuation (assessed up to 12 months)
Assess pharmacokinetics (PK) of epcoritamab	Terminal Elimination Half-Life (t 1/2)	From first dose and at multiple time points until treatment discontinuation (assessed up to 12 months)

Collaborators and Investigators

• Sponsor: Genmab
• Collaborators: AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2023
• Primary Completion (Estimated): June 14, 2026
• Study Completion (Estimated): June 28, 2026

Study Registration Dates

• First Submitted: November 29, 2022
• First Submitted That Met QC Criteria: December 14, 2022
• First Posted (Actual): December 21, 2022

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Subcutaneous; Bispecific antibody; DuoBody®; Anti-CD20; Anti-CD3; Double-hit lymphoma; Triple-hit lymphoma; Follicular grade 3B; T-cell/histiocyte rich LBCL; EPCORE
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, Large B-Cell, Diffuse; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carboxylic Acids; Piperidines; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide
• Other Study ID Numbers: GCT3013-06; 2021-005744-29 (EudraCT Number); jRCT2021230015 (Registry Identifier: Japan Registry for Clinical Trials (jRCT)); 1006219 (Other Identifier: IRAS ID; UK Research Summaries Database); 2023-504832-16-00 (Ctis: EU CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No