Epcoritamab + Lenalidomide for B-Cell Lymphoma

Overseen By Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Northwestern University

Must not be taking: Bispecific T-cell engagers

Disqualifiers: HIV, CNS disease, Cardiac disease, others

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

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

Compensation: Varies

Number of Visits: 32

Duration: 12 months

34 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of combining two treatments, epcoritamab and lenalidomide, for individuals with B-cell lymphoma that has either not responded to treatment or has recurred. Epcoritamab is an immunotherapy that helps the immune system target cancer cells, while lenalidomide enhances the immune system's ability to fight cancer. The trial aims to determine if using both treatments together is more effective. This trial may suit individuals with immunodeficiency-related large B-cell lymphoma who have experienced a relapse or whose disease has not responded to previous treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received chemotherapy or other antineoplastic agents (except certain antibodies, steroids, or radiation) within 1 week or 5 half-lives before joining the trial.

Is there any evidence suggesting that the combination of epcoritamab and lenalidomide is likely to be safe for humans?

Research has shown that both epcoritamab and lenalidomide have been tested for safety in patients with B-cell lymphoma. Epcoritamab has undergone various trials and can be safely used outside of a hospital, offering a more convenient treatment option. Some patients experienced side effects, but these were usually manageable.

Lenalidomide has also been widely studied. In one study, 54% of patients reported at least one significant side effect. However, lenalidomide is already used to treat other blood cancers, indicating a well-known safety record.

Overall, while both treatments can cause side effects, research suggests they are generally well-tolerated. Clinical trial participants receive close monitoring to manage any side effects that may occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of epcoritamab and lenalidomide for treating B-cell lymphoma because of its unique approach and potential benefits. Epcoritamab is an innovative bispecific antibody that targets both CD3 on T-cells and CD20 on B-cells, helping the immune system directly attack the cancer cells. While lenalidomide is already known for its immune-modulating effects, the combination with epcoritamab may enhance the overall anti-tumor activity. This dual-action strategy could offer a more effective treatment option compared to traditional therapies that mainly focus on chemotherapy or single-target approaches.

What evidence suggests that the combination of epcoritamab and lenalidomide might be an effective treatment for B-cell lymphoma?

In this trial, participants will receive a combination of epcoritamab and lenalidomide to treat aggressive B-cell lymphomas. Research has shown that epcoritamab, a treatment that aids the immune system in fighting cancer, is promising. Earlier studies indicated that 64.3% of patients responded well, and 47.6% went into complete remission. Lenalidomide, another immune-boosting treatment, has also proven effective, with about 42% of patients responding and 18% achieving complete remission. By combining these treatments, the trial aims to leverage the strengths of both to better treat large B-cell lymphoma that has returned or not responded to other treatments. ^{1 2 3 4 5}

Who Is on the Research Team?

Reem Karmali

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

This trial is for patients with immunodeficiency-related large B-cell lymphoma that has either not responded to previous treatments or has returned after treatment. Participants should have a type of non-Hodgkin's lymphoma and be in a relapsed or refractory state.

Inclusion Criteria

I have chronic hepatitis B but it's under control with treatment.

I agree to use birth control if I can become pregnant.

Patients must have measurable disease per Lugano criteria

Exclusion Criteria

My cancer did not respond or came back within 30 days after CAR-T therapy.

Patients with human immunodeficiency virus (HIV) with detectable viral load and CD4 count ≤350 cells/mm3 & not on treatment for more than 1 year

I have active cancer in my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive epcoritamab subcutaneously and lenalidomide orally in cycles repeating every 28 days for up to 12 months

12 months

Weekly visits during cycle 1, then multiple visits per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Visits at 30 days, 12, 18, and 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Epcoritamab
• Lenalidomide

Trial Overview The trial is testing the effectiveness of combining two drugs, Epcoritamab and Lenalidomide, on treating this specific lymphoma. Epcoritamab helps direct the immune system's T-cells to attack cancer cells, while Lenalidomide boosts the immune response against these cells.

How Is the Trial Designed?

Group I: Treatment (epcoritamab, lenalidomide) Experimental Treatment 6 Interventions

Patients receive epcoritamab SC weekly during cycle 1 and on days 1, 8, 15, and 22 of cycles 2-3, and day 1 of cycles 4-12. Patients also receive lenalidomide PO on days 1-21 of each cycle. Cycles repeat every 28 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo PET/CT and collection of blood samples throughout the study and may undergo MRI during screening.

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?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In the phase III AUGMENT trial, lenalidomide combined with rituximab significantly improved progression-free survival in patients with relapsed or refractory follicular lymphoma compared to placebo, showing particular benefit for elderly patients.

Lenalidomide has an acceptable safety profile, although it can cause more frequent cases of severe neutropenia, which can be managed with dosage adjustments and growth factor support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: A Review in Previously Treated Follicular Lymphoma. Blair, HA.[2021]

Lenalidomide significantly improves the complete response rate (CRR) in patients with diffuse large B-cell lymphoma (DLBCL), achieving a CRR of 47.7% compared to 37.8% in the control group, based on a meta-analysis of 6 randomized controlled trials involving 1938 patients.

While lenalidomide enhances progression-free survival (PFS), it is associated with a higher risk of severe hematological adverse events, particularly neutropenia and febrile neutropenia, indicating a trade-off between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of lenalidomide in diffuse large B-cell lymphoma: a meta-analysis of randomized controlled trials. Liu, J., Mi, R., Chen, L., et al.[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, 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]

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 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 immunomodulator approved for treating relapsed/refractory mantle cell lymphoma (MCL) after two prior therapies, showing significant activity in various B-cell non-Hodgkin lymphomas (NHL).

Combining lenalidomide with rituximab (R2) has demonstrated promising results in both first-line and relapsed/refractory settings, and ongoing trials are evaluating its use in combination with immunochemotherapy regimens like R-CHOP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comprehensive review of lenalidomide therapy for B-cell non-Hodgkin lymphoma. Witzig, TE., Nowakowski, GS., Habermann, TM., et al.[2020]

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 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]

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/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%.

4. 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 ...

5. 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 ...