A Study of Subcutaneously Injected Epcoritamab Plus Oral Lenalidomide Tablets Compared to Intravenously (IV) Infused Rituximab Plus IV Infused Gemcitabine and IV Infused Oxaliplatin in Adult Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Phase 3

Recruiting

• Conditions: Diffuse Large B-Cell Lymphoma
• Interventions: Drug: Rituximab; Drug: Epcoritamab; Drug: Lenalidomide; Drug: Oxaliplatin; Drug: Gemcitabine

• Registration Number: NCT06508658
• Lead Sponsor: Genmab

Brief Summary

B-cell Lymphoma is an aggressive and rare cancer of a type of immune cells (a white blood cell responsible for fighting infections). This study will assess how safe and effective epcoritamab plus lenalidomide (E-Len) is compared to rituximab plus gemcitabine and oxaliplatin (R-GemOx) )in treating adult participants with relapsed or refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL). Adverse events and change in disease condition will be assessed.

Epcoritamab is an investigational drug being developed for the treatment of DLBCL. Study doctors put the participants in 1 of 2 groups, called treatment arms. Each group receives a different treatment. Around 320 adult participants with R/R DLBCL will be enrolled in approximately 165 sites across the world.

Participants in arm A will receive subcutaneous (SC) injections of epcoritamab plus oral lenalidomide capsules (E-Len) for up to 12 cycles (each cycle is 28 days). Participants "in arm B will receive intrav... (IV) infused R-GemOx for up to 4 cycles (each cycle is 28 days)

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-07-11
• Study First Submitted QC: 2024-07-14
• Study First Posted: 2024-07-18
• Study Start: 2024-08-13
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-03
• Last Update Posted: 2025-03-04
• Primary Completion: 2028-01
• Study Completion: 2028-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 360

Inclusion Criteria

• Eastern Cooperative Oncology Group Performance status score of 0 to 2.

• Histologically confirmed CD20+ Diffuse Large B-Cell Lymphoma (DLBCL) and documented in the most recent and representative pathology report, inclusive of the following according to the World Health Organization (WHO) 2022 as per the protocol.

• Must have relapsed or refractory (R/R) disease and have been previously treated with at least 1 line of systemic antineoplastic therapy including anti-CD20 mAb-containing combination chemotherapy since DLBCL diagnosis.

• . Participant must meet at least 1 of the following criteria:

  • Failed prior autologous stem cell transplant (ASCT), defined as relapsed after ASCT or been refractory to ASCT.

  • Not be considered a candidate for ASCT due to age, performance status, comorbidities and/or insufficient response to prior treatment, or have refused ASCT.

  • Be ineligible for or unable to receive chimeric antigen receptor T-cell (CAR-T) meeting at least 1 of the following criteria:

    • Unable to receive CAR-T therapy due to fitness and/or comorbidity.
    • Lymphocyte apheresis failure.
    • Unwilling to receive CAR-T therapy.
    • Unable to receive CAR-T therapy due to financial, geographic, insurance, access, and/or manufacturing constraints.
    • Relapsed/progressed after having achieved at least a Partial Response (PR) or Complete Response (CR) while on prior CAR-T therapy.

• Must have measurable disease.

• Life expectancy > 3 months on standard of care treatment at the time of enrolling in the study

Exclusion Criteria

• Current evidence of primary central nervous system (CNS) lymphoma or known CNS involvement by lymphoma including leptomeningeal disease, at screening.
• History of prior treatment with a bispecific antibody targeting CD3 and CD20 or prior treatment with rituximab plus gemcitabine and oxaliplatin (R-GemOx) or gemcitabine and oxaliplatin (GemOx).
• Documented refractoriness to lenalidomide.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A: Epcoritamab Plus Lenalidomide (E-Len)	Lenalidomide	Participants will receive E-Len for up to 12 cycles (each cycle is 28 days).
Arm B: Rituximab Plus Gemcitabine and Oxaliplatin (R-GemOx)	Rituximab	Participants will receive R-GemOx for up to 4 cycles (each cycle is 28 days)
Arm B: Rituximab Plus Gemcitabine and Oxaliplatin (R-GemOx)	Oxaliplatin	Participants will receive R-GemOx for up to 4 cycles (each cycle is 28 days)
Arm B: Rituximab Plus Gemcitabine and Oxaliplatin (R-GemOx)	Gemcitabine	Participants will receive R-GemOx for up to 4 cycles (each cycle is 28 days)
Arm A: Epcoritamab Plus Lenalidomide (E-Len)	Epcoritamab	Participants will receive E-Len for up to 12 cycles (each cycle is 28 days).

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS)	Up to 4 Years	PFS is defined as the duration from the date of randomization to the date of disease progression determined per Lugano 2014 criteria as assessed by an independent review committee (IRC), or death, whichever occurs first.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Up to 4 Years	OS is defined as the time from randomization to death from any cause.
Percentage of Participants Who Achieve Minimal Residual Disease (MRD) Negativity Rate	Up to 4 Years	The MRD negativity rate is defined as the percentage of participants who achieve MRD negative status prior to the initiation of new anti-lymphoma therapy.
Percentage of Participants Who Achieve Complete response (CR)	Up to 4 Years	CR is defined as the percentage of participants who achieve CR determined by Lugano 2014 criteria, as assessed by an IRC that is blinded to treatment arm prior to the initiation of new anti-lymphoma therapy.

Trial Locations

Locations (122)

Hopital Saint Vincent de Paul /ID# 243070; 🇫🇷 Lille Cedex, France

Institut de cancérologie Strasbourg Europe (ICANS) /ID# 264068; 🇫🇷 Strasbourg, France

Adnan Menderes University /ID# 242418; 🇹🇷 Aydin, Turkey

Trakya University Medical Facu /ID# 242419; 🇹🇷 Edirne, Istanbul, Turkey

Ondokuz mayis University Facul /ID# 242412; 🇹🇷 Samsun, Turkey

Nottingham City Hospital /ID# 265129; 🇬🇧 Nottingham, Nottinghamshire, United Kingdom

UMHAT Sveti Georgi /ID# 242905; 🇧🇬 Plovdiv, Bulgaria

North Shore Hospital /ID# 266060; 🇳🇿 Auckland, New Zealand

Valkyrie Clinical Trials /ID# 269935; 🇺🇸 Los Angeles, California, United States

Lutheran Medical Center- Cancer Centers of Colorado /ID# 265823; 🇺🇸 Golden, Colorado, United States

Northwest Cancer Center - Dyer Clinic /ID# 269787; 🇺🇸 Dyer, Indiana, United States

Cancer Center of Kansas - Wichita /ID# 270117; 🇺🇸 Wichita, Kansas, United States

Gulfport Memorial Hospital /ID# 268104; 🇺🇸 Gulfport, Mississippi, United States

New York Medical College /ID# 265799; 🇺🇸 Valhalla, New York, United States

Thompson Cancer Survival Ctr /ID# 242149; 🇺🇸 Knoxville, Tennessee, United States

Community Cancer Trials Of Utah /ID# 271715; 🇺🇸 Ogden, Utah, United States

Canberra Hospital /ID# 265312; 🇦🇺 Canberra, Australian Capital Territory, Australia

Royal Prince Alfred Hospital /ID# 263242; 🇦🇺 Sydney, New South Wales, Australia

Wollongong Hospital /ID# 244646; 🇦🇺 Wollongong, New South Wales, Australia

Toowoomba Hospital /ID# 263243; 🇦🇺 Toowoomba, Queensland, Australia

Monash Health - Monash Medical Centre /ID# 262783; 🇦🇺 Clayton, Victoria, Australia

Royal Perth Hospital /ID# 243790; 🇦🇺 Perth, Western Australia, Australia

Universitair Ziekenhuis Brussel /ID# 242574; 🇧🇪 Jette, Bruxelles-Capitale, Belgium

Centre Hospitalier Epicura - site d'Hornu /ID# 265148; 🇧🇪 Boussu, Hainaut, Belgium

Université Catholique de Louvain-Namur - Centre Hospitalier Universitaire Dinant /ID# 242565; 🇧🇪 Yvoir, Namur, Belgium

Universitair Ziekenhuis Leuven /ID# 246671; 🇧🇪 Leuven, Vlaams-Brabant, Belgium

AZ-Delta /ID# 264740; 🇧🇪 Roeselare, West-Vlaanderen, Belgium

UMHAT Sveti Ivan Rilski /ID# 242389; 🇧🇬 Sofia, Bulgaria

SHAT Hematologic Diseases /ID# 242708; 🇧🇬 Sofia, Bulgaria

UMHAT Sveta Marina /ID# 262761; 🇧🇬 Varna, Bulgaria

Peking University Third Hospital /ID# 242941; 🇨🇳 Beijing, Beijing, China

Sun Yat-Sen University Cancer Center /ID# 242712; 🇨🇳 Guangzhou, Guangdong, China

Guangdong Provincial People's Hospital /ID# 242942; 🇨🇳 Guangzhou, Guangdong, China

The Second Hospital of Hebei Medical University /ID# 242944; 🇨🇳 Shijiazhuang, Hebei, China

Union Hospital affiliated to Tongji Medical College of Huazhong University of Sc /ID# 242702; 🇨🇳 Wuhan, Hubei, China

Hubei Cancer Hospital /ID# 242963; 🇨🇳 Wuhan, Hubei, China

The First Affiliated Hospital of Soochow University /ID# 242939; 🇨🇳 Suzhou, Jiangsu, China

The First Hospital of Jilin University /ID# 242940; 🇨🇳 Changchun, Jilin, China

Shandong Cancer Hospital /ID# 264036; 🇨🇳 Jinan, Shandong, China

Tianjin Cancer Hospital /ID# 243940; 🇨🇳 Tianjin, Tianjin, China

Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sc /ID# 243139; 🇨🇳 Tianjin, Tianjin, China

The Affiliated Cancer Hospital of Xinjiang Medical University /ID# 242966; 🇨🇳 Urumqi, Xinjiang, China

The second affiliated hospital of Zhejiang University school of medicine /ID# 243137; 🇨🇳 Hangzhou, Zhejiang, China

The First Affiliated Hospital of Wenzhou Medical University /ID# 263951; 🇨🇳 Wenzhou, Zhejiang, China

Klinicka bolnica Merkur /ID# 262619; 🇭🇷 Zagreb, Grad Zagreb, Croatia

Klinicki bolnicki centar Sestre milosrdnice /ID# 262620; 🇭🇷 Zagreb, Grad Zagreb, Croatia

Klinicki bolnicki centar Zagreb /ID# 262617; 🇭🇷 Zagreb, Grad Zagreb, Croatia

Klinicki bolnicki centar Osijek /ID# 262621; 🇭🇷 Osijek, Osjecko-baranjska Zupanija, Croatia

Klinički Bolnički Centar Rijeka /ID# 266004; 🇭🇷 Rijeka, Primorsko-goranska Zupanija, Croatia

Klinicki Bolnicki Centar (KBC) Split /ID# 262618; 🇭🇷 Split, Splitsko-dalmatinska Zupanija, Croatia

Fakultní nemocnice Hradec Králové - Sokolská /ID# 264071; 🇨🇿 Hradec Králové, Hradec Kralove, Czechia

Wellington Hospital /ID# 265966; 🇳🇿 Wellington, New Zealand

CHRU Tours - Hopital Bretonneau /ID# 244580; 🇫🇷 Tours CEDEX 9, Indre-et-Loire, France

Centre Hospitalier D'Avignon /ID# 243072; 🇫🇷 Avignon, Provence-Alpes-Cote-d Azur, France

Centre Hospitalier de la Cote Basque /ID# 243065; 🇫🇷 Bayonne, Pyrenees-Atlantiques, France

CHU Poitiers - La miletrie /ID# 243074; 🇫🇷 Poitiers, Vienne, France

CHU de CAEN - Hopital de la Cote de Nacre /ID# 243075; 🇫🇷 Caen, France

General Hospital of Athens Laiko /ID# 262809; 🇬🇷 Athens, Attiki, Greece

University General Hospital Attikon /ID# 242041; 🇬🇷 Athens, Attiki, Greece

General Hospital of Athens Evaggelismos and Ophthalmiatrio of Athens Polyclinic /ID# 242039; 🇬🇷 Athens, Greece

General University Hospital of Thessaloniki AXEPA /ID# 242038; 🇬🇷 Thessaloniki, Greece

Theageneio Anticancer Hospital /ID# 242036; 🇬🇷 Thessaloniki, Greece

Pecsi Tudomanyegyetem Klinikai Kozpont /ID# 262924; 🇭🇺 Pecs, Baranya, Hungary

Gyor-Moson-Sopron Varmegyei Petz Aladar Egyetemi Oktato Korhaz /ID# 262901; 🇭🇺 Gyor, Gyor-Moson-Sopron, Hungary

Debreceni Egyetem-Klinikai Kozpont /ID# 242451; 🇭🇺 Debrecen, Hajdu-Bihar, Hungary

Szabolcs-Szatmar-Bereg Varmegyei Oktatokorhaz /ID# 242468; 🇭🇺 Nyiregyhaza, Szabolcs-Szatmar-Bereg, Hungary

Semmelweis Egyetem /ID# 242455; 🇭🇺 Budapest, Hungary

Del-pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet /ID# 262923; 🇭🇺 Budapest, Hungary

Orszagos Onkologiai Intezet /ID# 242457; 🇭🇺 Budapest, Hungary

Fujita Health University Hospital /ID# 265968; 🇯🇵 Toyoake, Aichi, Japan

National Hospital Organization Shikoku Cancer Center /ID# 265977; 🇯🇵 Matsuyama, Ehime, Japan

Kyushu University Hospital /ID# 267624; 🇯🇵 Fukuoka-shi, Fukuoka, Japan

Fukushima Medical University Hospital /ID# 264667; 🇯🇵 Fukushima-shi, Fukushima, Japan

Sapporo Medical University Hospital /ID# 264928; 🇯🇵 Sapporo, Hokkaido, Japan

Kagoshima University Hospital /ID# 248259; 🇯🇵 Kagoshima-shi, Kagoshima, Japan

Tokai University Hospital /ID# 265433; 🇯🇵 Isehara, Kanagawa, Japan

Kansai Medical University Hospital /ID# 266018; 🇯🇵 Hirakata-shi, Osaka, Japan

Kindai University Hospital /ID# 265474; 🇯🇵 Osakasayama-shi, Osaka, Japan

Saitama Cancer Center /ID# 265277; 🇯🇵 Kitaadachi-gun, Saitama, Japan

University of Yamanashi Hospital /ID# 264671; 🇯🇵 Chuo, Yamanashi, Japan

Inje University - Busan Paik Hospital /ID# 262842; 🇰🇷 Busan, Busan Gwang Yeogsi, Korea, Republic of

Dong-A University Medical Center /ID# 262841; 🇰🇷 Busan, Busan Gwang Yeogsi, Korea, Republic of

Seoul National University Bundang Hospital /ID# 242405; 🇰🇷 Seongnam-si, Gyeonggido, Korea, Republic of

Keimyung University Dongsan Hospital /ID# 262840; 🇰🇷 Daegu, Gyeongsangbugdo, Korea, Republic of

Jeonbuk National University Hospital /ID# 242958; 🇰🇷 Jeonju, Jeonrabugdo, Korea, Republic of

Chonnam National University Hwasun Hospital /ID# 262843; 🇰🇷 Hwasun-gun, Jeonranamdo, Korea, Republic of

Seoul National University Hospital /ID# 242407; 🇰🇷 Seoul, Seoul Teugbyeolsi, Korea, Republic of

Asan Medical Center /ID# 242409; 🇰🇷 Seoul, Seoul Teugbyeolsi, Korea, Republic of

Samsung Medical Center /ID# 242408; 🇰🇷 Seoul, Seoul Teugbyeolsi, Korea, Republic of

The Catholic University of Korea, Seoul St. Marys Hospital /ID# 242406; 🇰🇷 Seoul, Seoul Teugbyeolsi, Korea, Republic of

Ulsan University Hospital /ID# 242956; 🇰🇷 Ulsan, Ulsan Gwang Yeogsi, Korea, Republic of

Medisch Centrum Leeuwarden /ID# 245501; 🇳🇱 Leeuwarden, Friesland, Netherlands

Jeroen Bosch Ziekenhuis, locatie 's-Hertogenbosch /ID# 265204; 🇳🇱 's-Hertogenbosch, Noord-Brabant, Netherlands

OLVG - Locatie Oost /ID# 263355; 🇳🇱 Amsterdam, Noord-Holland, Netherlands

St. Antonius Ziekenhuis /ID# 245197; 🇳🇱 Nieuwegein, Utrecht, Netherlands

Albert Schweitzer Ziekenhuis, locatie Dordwijk /ID# 263361; 🇳🇱 Dordrecht, Zuid-Holland, Netherlands

Pratia MCM Krakow /ID# 262882; 🇵🇱 Krakow, Malopolskie, Poland

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Bada /ID# 263314; 🇵🇱 Warsaw, Mazowieckie, Poland

Swietokrzyskie Centrum Onkologii Samodzielny Publiczny Zaklad Opieki Zdrowotnej /ID# 242436; 🇵🇱 Kielce, Swietokrzyskie, Poland

Aidport sp z o.o. /ID# 262766; 🇵🇱 Poznan, Wielkopolskie, Poland

Hospital da Luz /ID# 262965; 🇵🇹 Lisbon, Lisboa, Portugal

Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE /ID# 262961; 🇵🇹 Porto, Portugal

Unidade Local de Saude de Sao Joao, EPE /ID# 262962; 🇵🇹 Porto, Portugal

Fundeni Clinical Institute /ID# 266734; 🇷🇴 Bucharest, Bucuresti, Romania

Institutul Oncologic Prof Dr I Chiricuta /ID# 243753; 🇷🇴 Cluj Napoca, Cluj, Romania

Institutul Regional de Oncologie /ID# 244367; 🇷🇴 Jassi, Iasi, Romania

Spitalul Clinic Coltea /ID# 243694; 🇷🇴 Bucharest, Romania

Clinical Hospital Center Zvezdara /ID# 263059; 🇷🇸 Belgrade, Beograd, Serbia

Institute for Oncology and Radiology of Serbia /ID# 263055; 🇷🇸 Belgrade, Beograd, Serbia

University Clinical Center Serbia /ID# 263057; 🇷🇸 Belgrade, Beograd, Serbia

Clinical Hospital Center - Bežanijska Kosa /ID# 263053; 🇷🇸 Belgrade, Beograd, Serbia

University Clinical Center Nis /ID# 263701; 🇷🇸 Niš, Nisavski Okrug, Serbia

Institute for Oncology of Vojvodina /ID# 263052; 🇷🇸 Sremska Kamenica, Vojvodina, Serbia

University Clinical Center Vojvodina /ID# 264138; 🇷🇸 Novi Sad, Serbia

National Cancer Centre Singapore /ID# 267015; 🇸🇬 Singapore, Central Singapore, Singapore

National University Hospital /ID# 264016; 🇸🇬 Singapore, Singapore

Alberts Cellular Therapy /ID# 262720; 🇿🇦 Pretoria, Gauteng, South Africa

Haemalife Inc. /ID# 262719; 🇿🇦 Kuilsrivier, Western Cape, South Africa

National Taiwan University Hospital /ID# 243300; 🇨🇳 Taipei City, Taipei, Taiwan

China Medical University Hospital /ID# 242931; 🇨🇳 Taichung, Taiwan

Taichung Veterans General Hospital /ID# 242937; 🇨🇳 Taichung, Taiwan

National Cheng Kung University Hospital /ID# 243301; 🇨🇳 Tainan, Taiwan