Epcoritamab + Lenalidomide for B-Cell Lymphoma

(EPCORE DLBCL-4 Trial)

Recruiting at 211 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Genmab

Must not be taking: Bispecific antibodies

Disqualifiers: CNS lymphoma, Lenalidomide refractoriness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months for E-Len, 4 months for R-GemOx

360 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for Diffuse Large B-Cell Lymphoma (DLBCL), an aggressive cancer affecting certain white blood cells. Researchers aim to determine if combining epcoritamab (a type of immunotherapy) with lenalidomide is more effective than current treatments. Individuals with DLBCL that has recurred or not responded to previous treatments may be suitable candidates, especially if they have already tried therapies like stem cell transplants or CAR-T therapy without success. Participants will join one of three groups to receive different treatments and will attend regular hospital visits for check-ups and tests. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants access to potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop your current medications. It's best to discuss this with the study doctors to understand how your current medications might interact with the trial treatments.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that epcoritamab is generally safe for treating relapsed or refractory B-cell lymphoma. Common side effects include a temporary immune reaction called cytokine release syndrome, fever, tiredness, and low levels of neutrophils, a type of white blood cell. These side effects were manageable and did not prevent most patients from continuing treatment.

When combined with lenalidomide, the safety profile remains similar. Early results indicate that this combination is well-tolerated and effective against tumors in patients with diffuse large B-cell lymphoma (DLBCL).

Previous studies on the combination of rituximab, gemcitabine, and oxaliplatin (R-GemOx) in patients with DLBCL have shown promising results. The treatment was generally safe, although specific side effects were not detailed.

The trial is in an advanced phase, indicating that safety has been thoroughly evaluated. This suggests the treatments are expected to be well-tolerated, but participation still involves regular monitoring for side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for B-cell lymphoma because they offer new mechanisms of action compared to current options like rituximab, gemcitabine, and oxaliplatin. Epcoritamab is unique as it is a bispecific antibody designed to engage both T-cells and cancer cells, potentially leading to a more direct and potent immune response. Adding lenalidomide in the E-Len combination arm could enhance this immune response through its immunomodulatory effects, which is a different approach from standard chemotherapy regimens. These innovative strategies could provide more targeted and effective treatment options, offering hope for better outcomes for patients with B-cell lymphoma.

What evidence suggests that this trial's treatments could be effective for B-cell Lymphoma?

Research has shown that epcoritamab, one of the treatments in this trial, helps about 61% of patients with relapsed or hard-to-treat diffuse large B-cell lymphoma (DLBCL) improve when used alone. In these cases, about 38% of patients achieved complete remission, with no signs of the disease. In this trial, some participants will receive epcoritamab alone, while others will receive a combination of epcoritamab with lenalidomide. This combination has shown a similar improvement rate of 64.3%, with 47.6% of patients achieving complete remission. Another treatment option in this trial is rituximab combined with gemcitabine and oxaliplatin (R-GemOx), which has demonstrated an improvement rate of 83%, with half of the patients reaching complete remission. These findings suggest that the various treatments tested in this trial hold promising potential for combating this aggressive type of lymphoma. ^{1 5 6 7 8}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

Adults with relapsed or refractory Diffuse Large B-Cell Lymphoma who have tried at least one prior therapy, are not candidates for stem cell transplant due to various reasons, and cannot receive CAR-T therapy. They should be in a relatively stable condition as indicated by an ECOG score of 0 to 2.

Inclusion Criteria

I am not eligible for or have refused a stem cell transplant.

My lymphoma is confirmed to be CD20+ DLBCL by recent tests.

My cancer returned or did not respond after a stem cell transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Epcoritamab plus Lenalidomide for up to 12 cycles or Rituximab plus Gemcitabine and Oxaliplatin for up to 4 cycles

12 months for E-Len, 4 months for R-GemOx

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 4 years

What Are the Treatments Tested in This Trial?

Interventions

• Epcoritamab
• Gemcitabine
• Lenalidomide
• Oxaliplatin
• Rituximab

Trial Overview The trial is testing the effectiveness of two treatments: subcutaneous injections of epcoritamab plus oral lenalidomide capsules (E-Len) versus intravenous infusions of rituximab with gemcitabine and oxaliplatin (R-GemOx). Participants will be randomly assigned to either treatment arm.

How Is the Trial Designed?

Group I: Arm C: Epcoritamab Experimental Treatment 1 Intervention

Participants will receive epcoritamab for up to 12 cycles (each cycle is 28 days).

Group II: Arm B: Rituximab Plus Gemcitabine and Oxaliplatin (R-GemOx) Experimental Treatment 3 Interventions

Participants will receive R-GemOx for up to 4 cycles (each cycle is 28 days)

Group III: Arm A: Epcoritamab Plus Lenalidomide (E-Len) Experimental Treatment 2 Interventions

Participants will receive E-Len for up to 12 cycles (each cycle is 28 days).

Epcoritamab is already approved in United States, European Union for the following indications:

Approved in United States as Epkinly for:

• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy
• Diffuse large B-cell lymphoma after two or more lines of systemic therapy

Approved in European Union as Tepkinly for:

• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy
• Relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy

Who Is Running the Clinical Trial?

Genmab

Lead Sponsor

Trials

76

Recruited

15,300+

Dr. Jan van de Winkel

Genmab

Chief Executive Officer since 2010

PhD in Immunology, University of Utrecht

Dr. Judith Klimovsky

Genmab

Chief Medical Officer since 2019

MD, University of Copenhagen

AbbVie

Industry Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Published Research Related to This Trial

Lenalidomide enhances the immune response against tumor cells by boosting the activity of natural killer (NK) and T-cells, and it has shown clinical responses in patients with various types of B-cell lymphomas and relapsed/refractory chronic lymphocytic leukemia (CLL).

While lenalidomide has a favorable safety profile and is particularly suitable for elderly or chemotherapy-unfit patients, there are risks of serious side effects like tumor lysis syndrome, which complicate its use in certain patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The emerging role of lenalidomide in the management of lymphoid malignancies. Hernandez-Ilizaliturri, FJ., Batoo, SA.[2021]

In a phase II trial involving 66 patients with untreated follicular lymphoma, the combination of lenalidomide and rituximab achieved a high overall response rate of 95% and a complete response rate of 72%, indicating strong efficacy.

The treatment was associated with low rates of severe toxicity (grade 3-4), with a 5-year overall survival rate of 100%, suggesting that lenalidomide plus rituximab could be a safe and effective alternative to traditional chemotherapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of lenalidomide plus rituximab in previously untreated follicular non-Hodgkin's lymphoma (NHL): CALGB 50803 (Alliance). Martin, P., Jung, SH., Pitcher, B., et al.[2023]

Lenalidomide is an orally bioavailable immunomodulator that has shown significant antitumor activity in treating various types of B-cell lymphomas, including mantle cell lymphoma and diffuse large B-cell lymphoma.

The drug has a favorable safety profile and is effective both as a standalone treatment and in combination with other therapies, marking a shift from traditional chemotherapy approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving role of lenalidomide in non-Hodgkin lymphoma. Galanina, N., Petrich, A., Nabhan, C.[2019]

Lenalidomide is an FDA-approved immunomodulatory drug that shows strong efficacy in treating multiple myeloma and certain B-cell malignancies, particularly when combined with monoclonal antibodies like rituximab.

The drug works by modifying the tumor microenvironment and enhancing the activity of T and natural-killer (NK) cells, demonstrating excellent tolerability and potential to change treatment approaches for non-Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comprehensive review of lenalidomide in B-cell non-Hodgkin lymphoma. Arora, M., Gowda, S., Tuscano, J.[2022]

Lenalidomide, an immunomodulatory drug, shows promise in treating diffuse large B-cell lymphoma (DLBCL) due to its multiple mechanisms of action that may enhance the effectiveness of existing immunochemotherapy treatments.

Current survival rates for DLBCL indicate a need for new treatment options, and lenalidomide has demonstrated potential benefits in both relapsed/refractory cases and as a first-line treatment based on recent clinical trial results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in diffuse large B-cell lymphoma. Thieblemont, C., Delfau-Larue, MH., Coiffier, B.[2021]

In a phase II trial involving 217 patients with relapsed or refractory aggressive non-Hodgkin's lymphoma, lenalidomide demonstrated an overall response rate of 35%, with 13% achieving complete remission and 22% achieving partial remission.

Lenalidomide was found to be well tolerated, although myelosuppression was a common side effect, particularly with grade 4 neutropenia occurring in 17% of patients, indicating that while effective, monitoring for blood-related side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma. Witzig, TE., Vose, JM., Zinzani, PL., et al.[2022]

Lenalidomide is an effective oral immunomodulatory drug that enhances the immune response against tumor cells, particularly in non-Hodgkin lymphoma, by stimulating natural killer (NK) cells and promoting their cytotoxic activity.

The drug's efficacy is linked to its interaction with the E3 ubiquitin ligase cereblon, which is crucial for its antitumor effects, and it shows improved responses when combined with other treatments like rituximab, making it a valuable option for various lymphoma subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanisms of Action of Lenalidomide in B-Cell Non-Hodgkin Lymphoma. Gribben, JG., Fowler, N., Morschhauser, F.[2023]

In a phase II trial involving 50 patients with indolent B-cell or mantle cell lymphomas who were previously resistant to rituximab, the combination of lenalidomide and rituximab resulted in a significant increase in overall response rate from 30.2% after lenalidomide alone to 62.8% after adding rituximab.

The median progression-free survival for patients receiving the lenalidomide-rituximab combination was 22.2 months, which was significantly longer than the 9.13 months observed with prior rituximab treatment, indicating that this combination can effectively overcome previous resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of Lenalidomide and Rituximab Overcomes Rituximab Resistance in Patients with Indolent B-cell and Mantle Cell Lymphomas. Chong, EA., Ahmadi, T., Aqui, NA., et al.[2022]

Lenalidomide is an FDA-approved immunomodulatory drug effective in treating bortezomib-resistant mantle-cell lymphoma and shows promise in various other lymphoma subtypes.

Its mechanism of action involves enhancing immune responses, such as T-cell and NK-cell activity, and ongoing clinical trials are focused on identifying biomarkers to improve its integration into lymphoma treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in non-Hodgkin lymphoma: biological perspectives and therapeutic opportunities. Kritharis, A., Coyle, M., Sharma, J., et al.[2021]

Citations

1. ashpublications.org ashpublications.org/blood/article/146/18/2177/546196/Real-world-outcomes-of-patients-with-aggressive-B

Real-world outcomes of patients with aggressive B-cell ... A total of 201 of 245 patients (82.0%) were efficacy-evaluable (124 treated with epcoritamab [80%], and 77 treated with glofitamab [87%]).

2. news.abbvie.com news.abbvie.com/2025-09-03-AbbVie-Announces-Updated-Results-From-Phase-2-EPCORE-R-NHL-6-Study-Evaluating-the-Potential-for-Outpatient-Monitoring-of-Epcoritamab-in-Patients-With-Relapsed-Refractory-R-R-Diffuse-Large-B-Cell-Lymphoma-DLBCL

AbbVie Announces Updated Results From Phase 2 ... The study also showed an overall response rate (ORR) of 64.3% and a complete response (CR) rate of 47.6%, at a median follow-up of 5.8 months, ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39322711/

Epcoritamab in relapsed/refractory large B-cell lymphoma As of April 21, 2023, overall response rate was 63.1% and complete response (CR) rate was 40.1%. Estimated 24-month progression-free survival ( ...

4. epkinly.com epkinly.com/clinical-trial-results

Clinical Trial Results - EPKINLY® (epcoritamab-bysp) DLBCL: In a clinical study of 148 patients receiving EPKINLY, 61% (90 patients) achieved remission: complete remission in 38% (56 patients) and partial ...

5. ir.genmab.com ir.genmab.com/news-releases/news-release-details/genmab-announces-updated-results-phase-2-epcorer-nhl-6-study

Genmab Announces Updated Results from Phase 2 ... The study also demonstrated an overall response rate (ORR) of 64.3% and a complete response (CR) rate of 47.6%, at a median follow up of 5.8 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40434509/

Efficacy and safety of epcoritamab in Japanese patients ... Results: As of July 12, 2024, 36 patients received epcoritamab (median follow-up, 36.7 months). Overall/complete response rates were 56%/47%.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265025023766

Safety and Efficacy of Epcoritamab in Relapsed, Refractory ... Our study demonstrated pooled ORR of 73% in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, 71.7% for DLBCL and 82.5% for FL. However, ...

8. nature.com nature.com/articles/s41375-024-02410-8

Epcoritamab in relapsed/refractory large B-cell lymphoma The most common treatment-emergent adverse events were cytokine release syndrome (51.0%), pyrexia (24.8%), fatigue (24.2%), and neutropenia ( ...