Epcoritamab + Lenalidomide for B-Cell Lymphoma

(EPCORE DLBCL-4 Trial)

Recruiting at 143 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

Trial Summary

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.

What data supports the effectiveness of the drug combination Epcoritamab and Lenalidomide for B-Cell Lymphoma?

Research shows that Lenalidomide, when combined with Rituximab, has shown impressive effectiveness in treating B-cell lymphomas, including overcoming resistance to Rituximab. This suggests that Lenalidomide can enhance the effectiveness of other treatments in B-cell lymphomas. ^{1 2 3 4 5}

What makes the drug Epcoritamab + Lenalidomide unique for B-cell lymphoma?

Epcoritamab + Lenalidomide is unique because it combines Epcoritamab, a bispecific antibody that targets CD3 and CD20 to engage T-cells in attacking B-cell lymphoma, with Lenalidomide, an immunomodulatory drug that enhances immune cell activity and has shown effectiveness in various lymphoma subtypes. This combination leverages both direct tumor targeting and immune system enhancement, offering a novel approach compared to traditional therapies. ^{5 6 7 8 9}

What is the purpose of this trial?

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.

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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 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]

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]

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 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, 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

The evolving role of lenalidomide in non-Hodgkin lymphoma. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Combination of Lenalidomide and Rituximab Overcomes Rituximab Resistance in Patients with Indolent B-cell and Mantle Cell Lymphomas. [2022]

3. England pubmed.ncbi.nlm.nih.gov

A comprehensive review of lenalidomide in B-cell non-Hodgkin lymphoma. [2022]

4. England 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). [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Mechanisms of Action of Lenalidomide in B-Cell Non-Hodgkin Lymphoma. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Lenalidomide in non-Hodgkin lymphoma: biological perspectives and therapeutic opportunities. [2021]

7. England pubmed.ncbi.nlm.nih.gov

The emerging role of lenalidomide in the management of lymphoid malignancies. [2021]

8. England 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. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Lenalidomide in diffuse large B-cell lymphoma. [2021]