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: Epcoritamab; Drug: Rituximab; 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 3 groups, called treatment arms. Each group receives a different treatment. Around 360 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 intravenously (IV) infused R-GemOx for up to 4 cycles (each cycle is 28 days). Participants in arm C will receive SC injections of epcoritamab for up to 12 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: 2025-09
• Last Update Submitted: 2025-09-01
• Last Update Posted: 2025-09-03
• Primary Completion: 2028-01
• Study Completion: 2028-01-01

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 high-dose therapy (HDT)-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 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 C: Epcoritamab	Epcoritamab	Participants will receive epcoritamab for up to 12 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).
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)

Primary Outcome Measures

Name	Time	Method
Arm A vs Arm B: 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
Arm A vs Arm B: 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.
Arm A vs Arm B: Overall Survival (OS)	Up to 4 Years	OS is defined as the time from randomization to death from any cause.
Arm A vs Arm B: 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.

Trial Locations

Locations (155)

City Of Hope - Atlanta /ID# 273092; 🇺🇸 Newnan, Georgia, United States

City Of Hope - Chicago /ID# 274430; 🇺🇸 Zion, Illinois, United States

Fundaleu /Id# 242789; 🇦🇷 Ciudad Autonoma de Buenos Aire, Buenos Aires F.D., Argentina

Guangdong Provincial Peoples Hospital /ID# 242942; 🇨🇳 Guangzhou, Guangdong, China

The Second Affiliated Hospital of Zhejiang University School of Medicine /ID# 243137; 🇨🇳 Hangzhou, Zhejiang, China

Shonankamakura General Hospital /ID# 277671; 🇯🇵 Kamakura, Kanagawa, Japan

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

City of Hope National Medical Center /ID# 273338; 🇺🇸 Duarte, California, United States

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

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

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