A Phase 3 Trial of Epcoritamab vs Investigator's Choice Chemotherapy in Relapsed/Refractory (R/R) Diffuse Large B-cell Lymphoma (DLBCL)

NCT ID: NCT04628494

Last Updated: 2025-11-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 484 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-13
• Study Completion Date: 2028-04-30

Brief Summary

The purpose of this trial is to find out if epcoritamab, also known as EPKINLY™ and GEN3013, is safe and works well as treatment for participants with DLBCL that are not responding to treatment, have grown in size, or have come back following treatment with at least 1 prior systemic cancer therapy. All participants in this trial will be randomly assigned to receive either epcoritamab or a pre-specified investigator's choice (standard of care) chemotherapy (either rituximab + gemcitabine + oxaliplatin [R-GemOx], or bendamustine + rituximab [BR]). Participants must have failed or be ineligible to receive an autologous stem cell transplant (ASCT).

Epcoritamab will be injected under the skin. Investigator's choice chemotherapy will be given intravenously.

Trial details include:

• The trial duration will be up to 5 years after last participant is randomized.
• All trial participants have a 21-day screening period, a treatment period, and a follow-up period that continues until death.
• The estimated trial duration for an individual participant depends upon the treatment arm assigned:

• Participants who receive epcoritamab will have 28-day treatment cycles. Epcoritamab will be given once weekly for the first 3 months, then every other week for 6 months, then every 28 days until lymphoma progression or unacceptable adverse events.
• Participants who receive investigator's choice (standard of care) chemotherapy will receive treatments either:

• R-GemOx: On Day 1 (or Day 1 & Day 2), and Day 15 (or Day 15 & Day 16) every 28 days, for up to 4 months; or
• BR: On Day 1 and Day 2 every 3 weeks for up to 4.5 months.

Detailed Description

The trial is an open label, multi-center, global phase-3 randomized trial of epcoritamab. The goal of this randomized trial is to evaluate the efficacy of epcoritamab (GEN3013, DuoBody®-CD3xCD20) compared to investigator's choice of chemotherapy, in participants with relapsed, refractory DLBCL who have failed or are ineligible for high-dose chemotherapy and autologous stem cell transplant (HDT-ASCT). No change in chemotherapy is permitted for participants during the treatment phase of the trial.

Overall Survival (OS) is the primary endpoint in USA and in China, with the analysis population including all randomized participants. OS/Progression Free Survival (PFS) are dual-primary endpoints for rest of the world (outside US and China), with the analysis population also including all participants randomized.

The China sub-study of GCT3013-05 is registered under NCT07226752.

Conditions

Diffuse Large B-cell Lymphoma

Keywords

double-hit DLBCL; triple-hit DLBCL; follicular grade 3B; transformed DLBCL; T-cell histiocytes-rich large B cell lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Epcoritamab (GEN3013; DuoBody®CD3xCD20)

Epcoritamab will be administered in Cycles of 28 days until any of the discontinuation criteria is met

Group Type: EXPERIMENTAL

Epcoritamab

Intervention Type: BIOLOGICAL

Following mandatory pre-medication, participants will be administered epcoritamab as a subcutaneous injection.

Investigator's choice of chemotherapy

R-GemOx will be administrated in Cycles of 28 days until maximum cycles completion or any of the discontinuation criteria is met

BR will be administrated in Cycles of 21 days until maximum cycles completion or any of the discontinuation criteria is met

Group Type: ACTIVE_COMPARATOR

Investigator's Choice Chemotherapy

Intervention Type: DRUG

Following mandatory pre-medication, participants will be administered intravenously either BR or R-GemOx.

Interventions

Epcoritamab

Following mandatory pre-medication, participants will be administered epcoritamab as a subcutaneous injection.

Intervention Type: BIOLOGICAL

Investigator's Choice Chemotherapy

Following mandatory pre-medication, participants will be administered intravenously either BR or R-GemOx.

Intervention Type: DRUG

Other Intervention Names

GEN3013; DuoBody®-CD3xCD20; EPKINLY™; BR or R-GemOx

Eligibility Criteria

Inclusion Criteria

1. Relapsed or refractory disease and previously treated with at least 1 line of systemic antineoplastic therapy including anti-CD20 monoclonal antibody (mAb)-containing combination chemotherapy since lymphoma diagnosis

2. One of the confirmed histologies below with CD20-positivity:

1. DLBCL, not otherwise specified (NOS), including de novo or histologically transformed from follicular lymphoma (FL)

2. "Double-hit" or "triple-hit" DLBCL (technically classified in World Health Organization (WHO) 2016 as high-grade B-cell lymphoma (HGBCL), with MYC and BCL2 and/or BCL6 translocations), including de novo or histologically transformed from FL

3. FL Grade 3B

4. T-cell/histiocyte-rich large B-cell lymphoma

3. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0-2

4. Failed previous HDT-ASCT or not eligible for high-dose therapy autologous stem cell transplant (HDT-ASCT) at screening

5. Participants must have detectable disease by positron emission tomography (PET) scan and measurable by computed tomography (CT) scan or magnetic resonance imaging (MRI)

6. Acceptable renal and liver function

7. Life expectancy >2 months on standard of care treatment

Exclusion Criteria

1. Primary Central Nervous System (CNS) tumor or known CNS involvement

2. Any prior therapy with a bispecific antibody targeting CD3 and CD20

3. Major surgery within 4 weeks prior to randomization

4. Chemotherapy and other non-investigational antineoplastic agents (except CD20 mAbs) within 4 weeks or 5 half-lives (whichever is shorter) prior to randomization

5. Any investigational drug within 4 weeks or 5 half-lives, whichever is longer, prior to randomization

6. Autologous stem cell transplant (ASCT) within 100 days of randomization

7. Treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 100 days prior to randomization

8. Seizure disorder requiring anti-epileptic therapy

9. Clinically significant cardiac disease

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: collaborator

Genmab

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Indiana Blood and Marrow Transplantation

Indianapolis, Indiana, United States

Community Health Network Cancer Center North

Indianapolis, Indiana, United States

University of Kentucky Markey Cancer Center

Lexington, Kentucky, United States

Henry Ford Health System

Jackson, Michigan, United States

MMCORC Attn Delaney Anderson

Saint Louis Park, Minnesota, United States

MD Anderson Cancer Center at Cooper

Camden, New Jersey, United States

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States

The Christ Hospital Cancer Center

Cincinnati, Ohio, United States

TriHealth Cancer Institute- Good Samaritan Hospital

Cincinnati, Ohio, United States

Brooke Army Medical Center

Fort Sam Houston, Texas, United States

Community Cancer Trials of Utah

Ogden, Utah, United States

LDS Hospital

Salt Lake City, Utah, United States

Virginia Commonwealth University (VCU) Massey Cancer Center

Richmond, Virginia, United States

North Star Lodge Cancer Center

Yakima, Washington, United States

Waukesha Memorial Hospital

Waukesha, Wisconsin, United States

Flinders Medical Centre

Bedford Park, , Australia

Concord Repatriation General Hospital

Concord, , Australia

Peninsula Private Hospital Clinical Trials Unit

Frankston, , Australia

Icon Cancer Centre Corporate Office

South Brisbane, , Australia

Calvary Mater Newcastle

Waratah, , Australia

Westmead Hospital

Westmead, , Australia

Ordensklinikum Linz Barmherzige Schwestern

Linz, , Austria

Ordensklinikum Linz GmbH Elisabethinen

Linz, , Austria

Uniklinikum Salzburg, Universitätsklinik für Innere Medizin III der PMU

Salzburg, , Austria

ZNA Middelheim

Antwerp, , Belgium

AZ Sint-Jan

Bruges, , Belgium

Institut Jules Bordet

Brussels, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

UZ Brussel

Jette, , Belgium

Hôpital de Jolimont

La Louvière, , Belgium

Universitair Ziekenhuis gasthuisberg Leuven

Leuven, , Belgium

AZ Nikolaas- Verenigde Ziekenhuizen van Waas en Durme

Sint-Niklaas, , Belgium

AZ Turnhout, Campus Sint-Elisabeth

Turnhout, , Belgium

CHU de Quebec-Universite Laval

Québec, , Canada

Aalborg Universitetshospital

Aalborg, , Denmark

Aarhus University Hospital, Department of Hematology, Clinical Research Unit C116

Aarhus, , Denmark

Clinical Research Unit, Roskilde Sygehus

Roskilde, , Denmark

Vejle Hospital

Vejle, , Denmark

HUS Cancer Center/ Clinical Trial Unit

Helsinki, , Finland

Oulu university hospital, Department of hematology

Oulu, , Finland

Audrey ALEME

Amiens, , France

Centre Hospitalier de la Côte Basque

Bayonne, , France

CHRU de Brest - Hospital Morvan

Brest, , France

CHU Caen - IHBN

Caen, , France

Groupe Hospitalier de La Rochelle

La Rochelle, , France

CHU de LIMOGES

Limoges, , France

Centre Léon Bérard

Lyon, , France

Hopital de la Conception APHM

Marseille, , France

CHU de Nantes - Hôtel Dieu

Nantes, , France

Centre Antoine Lacassagne

Nice, , France

Clinique Victor Hugo

Paris, , France

Hôpital Saint-Louis

Paris, , France

CHU de Bordeaux Hôpital Haut-Lévêque

Pessac, , France

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

CHU de Poitiers - Hôpital la Milétrie

Poitiers, , France

Centre Hospitalier Rene Dubos

Pontoise, , France

Ch Cornouaille

Quimper, , France

Centre Henri Becquerel

Rouen, , France

CHRU Tours Hôpital Bretonneau

Tours, , France

Uniklinik Köln, Klinik I für Innere Medizin, CIO Gebäude 70, 5.094

Cologne, , Germany

Universitaetsklinikum Essen

Essen, , Germany

Universitätsklinikum Schleswig-Holstein Medizinische Klinik II Hämatologie und Onkologie

Kiel, , Germany

Universitätsklinikum Würzburg

Würzburg, , Germany

National Institute of Oncology

Budapest, , Hungary

Semmelweis Egyetem Belgyógyászati és Onkológiai Klinika

Budapest, , Hungary

Debreceni Egyetem Klinikai Kozpont, Belgyogyaszati Klinika, Hematologia

Debrecen, , Hungary

Belgyógyászati osztály Markhot Ferenc Kórház

Eger, , Hungary

Petz Aladar Egyetemi Oktato Korhaz

Győr, , Hungary

Josa Andras Teaching Hospital, Hematology Dept

Nyíregyháza, , Hungary

University of Pecs 1st. Internal medicine Clinic Dept. Hematology

Pécs, , Hungary

Szegedi Tudományegyetem II. sz. Belgyogyaszat, Hematologia

Szeged, , Hungary

Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz

Székesfehérvár, , Hungary

Bnai Zion Medical Center

Haifa, , Israel

Rambam Health Care Center

Haifa, , Israel

Hadassah University Hospital

Jerusalem, , Israel

Shaare Zedek Medical Center

Jerusalem, , Israel

Sourasky Medical Center

Tel Aviv, , Israel

IRCCS Istituto Tumori Giovanni Paolo II Bari

Bari, , Italy

Azienda Socio Sanitaria Territoriale Sette Laghi (Presidio Ospedale di Circolo e Fondazione Macchi)

Bergamo, , Italy

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)

Brescia, , Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.)

Meldola, , Italy

Istituto Oncologico Europeo

Milan, , Italy

San Raffaele Hospital

Milan, , Italy

Azienda Ospedaliero - Universitaria Maggiore delle Carita SCDU Ematologia building C

Novara, , Italy

Fondazione IRCCS Policlinico San matteo

Pavia, , Italy

Ospedale Santa Maria delle Croci

Ravenna, , Italy

Azienda Ospedaliera Universitaria Policlinico Umberto I Università di Roma La Sapienza, Dip Med Tra

Rome, , Italy

IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, , Italy

Azienda Sanitaria Universitaria Giuliano Isontina (ASU GI) Ospedale Maggiore di Trieste

Trieste, , Italy

SC di Ematologia - AON SS Antonio e Biagio e Cesare Arrigo

Venezia, , Italy

Kyushu University Hospital

Fukuoka, , Japan

Fukushima Medical University Hospital

Fukushima, , Japan

Chugoku Central Hospital

Fukuyama, , Japan

Hokkaido University Hospital

Hokkaido, , Japan

National Cancer Center Hospital East

Kashiwa, , Japan

Kyoto University Medical Hospital

Kyoto, , Japan

Matsuyama Red Cross Hospital

Matsuyama, , Japan

Mie University Hospital

Mie, , Japan

Japanese Red Cross Nagoya Daini Hospital

Nagoya, , Japan

NHO Nagoya Medical Center

Nagoya, , Japan

Okayama University Hospital

Okayama, , Japan

Kindai University Hospital

Ōsaka-sayama, , Japan

Tohoku University Hospital

Sendai, , Japan

Keio University Hospital

Tokyo, , Japan

National Cancer Center Hospital

Tokyo, , Japan

Tokai University Hospital

Tokyo, , Japan

Fujita Health University Hospital

Toyoake, , Japan

Yamagata University Hospital

Yamagata, , Japan

Rijnstate Arnhem

Arnhem, , Netherlands

Amphia Ziekenhuis, Interne Geneeskunde, Oncologie. Route 43

Breda, , Netherlands

Albert Schweitzer Ziekenhuis

Dordrecht, , Netherlands

Admiraal de Ruyter Ziekenhuis

Goes, , Netherlands

Bravis Ziekenhuis

Roosendaal, , Netherlands

Erasmus MC

Rotterdam, , Netherlands

Franciscus Gasthuis And Vlietland

Rotterdam, , Netherlands

Oslo University Hospital location Radium hospital

Oslo, , Norway

St. Olavs Hospital HF

Trondheim, , Norway

Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii

Gdansk, , Poland

Pratia Onkologia Katowice

Katowice, , Poland

Pratia MCM Kraków

Krakow, , Poland

Instytut Centrum Zdrowia Matki Polki

Lodz, , Poland

Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii

Lodz, , Poland

Centrum Medyczne Pratia Poznan

Skorzewo, , Poland

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu

Wroclaw, , Poland

State Autonomous Institution of Healthcare Republican Clinical Oncological Dispensary of the Ministr

Kazan', , Russia

Federal State Budgetary Institution of Science

Moscow, , Russia

Federal State Budgetary Institution

Moscow, , Russia

State Budgetary Institution of Healthcare of Nizhniy Novgorod region, 1st inpatient facility, 5th fl

Nizhny Novgorod, , Russia

Federal State Budgetary Institution V.A. Almazov National Medical Research Center of the Ministry of

Saint Petersburg, , Russia

State Budgetary Institution of Healthcare Leningrad Regional Clinical Hospital

Saint Petersburg, , Russia

National University Hospital

Kent Ridge, , Singapore

Clinical Trials and Research Centre

Singapore, , Singapore

National Cancer Centre Singapore

Singapore, , Singapore

Dong-A University Hospital

Busan, , South Korea

Pusan National University Hospital

Busan, , South Korea

Pusan National University Hosptial

Busan, , South Korea

Keimyung University Dongsan Hospital

Daegu, , South Korea

Chonbuk National University Hospital

Geumam, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Seoul National University Bundang Hospital

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

The Catholic University of Korea Seoul St. Marys Hospital

Seoul, , South Korea

Ulsan University Hospital

Ulsan, , South Korea

ICO Badalona - Hospital Universitari Germans Trias i Pujol

Badalona, , Spain

ICO l'Hospitalet - Hospital Duran i Reynals

Barcelona, , Spain

Hospita Universitario Puerta Del Mar

Cadiz, , Spain

Hospital San Pedro de Alcántara

Cáceres, , Spain

Hospital Universitario Reina Sofía

Córdoba, , Spain

Hospital Arnau de Vilanova

Lleida, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario Fundacion Jimenez Diaz

Madrid, , Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Md Anderson Cancer Center

Madrid, , Spain

Hospital Universitario de Salamanca

Salamanca, , Spain

Hospital Universitario Marqués de Valdecilla

Santander, , Spain

Hospital Universitario Virgen De Valme

Seville, , Spain

Hospital Universitario Virgen del Rocío

Seville, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Karolinska university Hospital

Stockholm, , Sweden

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

National Cheng Kung University Hospital

Tainan, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Tri-Service General Hospital

Taipei, , Taiwan

Ankara University Medical Faculty

Ankara, , Turkey (Türkiye)

Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi

Ankara, , Turkey (Türkiye)

Gazi University Medical Faculty

Ankara, , Turkey (Türkiye)

Amerikan Hospital

Istanbul, , Turkey (Türkiye)

Iqvia Tibbi Istatistik

Istanbul, , Turkey (Türkiye)

Istanbul University Cerrahpasa - Cerrahpasa Tip Fakultesi

Istanbul, , Turkey (Türkiye)

Istanbul University Medical Faculty

Istanbul, , Turkey (Türkiye)

Dokuz Eylul University Medical Faculty

Izmir, , Turkey (Türkiye)

Ege University Medical Faculty

Izmir, , Turkey (Türkiye)

Tekirdag Namik Kemal University

Tekirdağ, , Turkey (Türkiye)

Karadeniz Technical University

Trabzon, , Turkey (Türkiye)

Haematology - University Hospitals Birmingham NHS Foundation Trust

Birmingham, , United Kingdom

Guys and St Thomas NHS Foundation Trust

London, , United Kingdom

Hammersmith Hospital

London, , United Kingdom

Norfolk and Norwich University Hospitals NHS Foundation Trust

Norwich, , United Kingdom

Nottingham University Hospitals NHS Trust

Nottingham, , United Kingdom

Derriford Hospital

Plymouth, , United Kingdom

University Hospital Southampton

Southampton, , United Kingdom

Royal Marsden NHS Foundation Trust (Sutton)

Sutton, , United Kingdom

Royal Cornwall Hospital

Truro, , United Kingdom

Countries

China; United States; Australia; Austria; Belgium; Canada; Denmark; Finland; France; Germany; Hungary; Israel; Italy; Japan; Netherlands; Norway; Poland; Russia; Singapore; South Korea; Spain; Sweden; Taiwan; Turkey (Türkiye); United Kingdom

Other Identifiers

286972

Identifier Type: OTHER

Identifier Source: secondary_id

2023-504830-23-00

Identifier Type: CTIS

Identifier Source: secondary_id

2020-003016-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

jRCT2021220017

Identifier Type: REGISTRY

Identifier Source: secondary_id

CTR20221558

Identifier Type: REGISTRY

Identifier Source: secondary_id

MOH_2021-01-18_009672

Identifier Type: REGISTRY

Identifier Source: secondary_id

NL75079.056.20

Identifier Type: REGISTRY

Identifier Source: secondary_id

GCT3013-05

Identifier Type: -

Identifier Source: org_study_id