Epcoritamab +/- Lenalidomide for Non-Hodgkin's Lymphoma

(EPCORE DLBCL-3 Trial)

Not currently recruiting at 117 trial locations

Overseen By Genmab Trial Information

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: Genmab

Must not be taking: Antineoplastics, Vaccines, Antiepileptics, others

Disqualifiers: Infections, Cardiovascular disease, CNS tumor, 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: Unknown

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new antibody treatment, epcoritamab, alone or with lenalidomide, for individuals with Diffuse Large B-Cell Lymphoma (DLBCL). It targets newly diagnosed elderly patients who cannot tolerate typical chemotherapy. Participants will receive either epcoritamab alone or with lenalidomide, with an equal chance of receiving either option. Ideal candidates are those diagnosed with CD20+ large cell lymphoma who cannot undergo standard chemotherapy due to age or other health issues. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer care.

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 certain treatments like non-investigational cancer drugs or investigational drugs within 4 weeks before starting the trial.

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

Research has shown that epcoritamab, the antibody used in this trial, has a manageable safety profile. In previous studies, patients with B-cell non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL), tolerated it well. The side effects aligned with expectations for this type of treatment, indicating general safety.

For the combination of epcoritamab and lenalidomide, studies have also demonstrated positive results and manageable safety. Patients with certain types of lymphoma who received this combination experienced significant benefits, and the safety outcomes matched expectations from similar treatments.

Overall, both treatments—epcoritamab alone and with lenalidomide—have demonstrated safety in past research, making them promising options for patients in this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Epcoritamab for Non-Hodgkin's Lymphoma because it offers a novel approach by directly engaging the immune system. Unlike traditional treatments such as chemotherapy, Epcoritamab is a bispecific antibody that targets both CD3 on T-cells and CD20 on B-cells, effectively recruiting the body's own immune cells to attack the cancerous B-cells. The combination of Epcoritamab with Lenalidomide further enhances the immune response, potentially leading to better outcomes. This dual strategy could provide a more targeted attack on lymphoma cells, reducing the side effects typically seen with conventional therapies.

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

Research has shown that epcoritamab, one of the treatments in this trial, yields promising results for patients with aggressive B-cell lymphomas when used alone. In one study, about 64.3% of patients responded well, with nearly half experiencing complete remission, meaning no signs of cancer were found. The benefits lasted a long time, with most patients maintaining improvements for over a year.

Another treatment arm in this trial combines epcoritamab with lenalidomide. This combination also shows strong potential, with trials indicating a similar response rate of 63%, and 40% of patients achieving complete remission. These findings suggest that both treatment options in this trial effectively manage symptoms of non-Hodgkin's lymphoma, especially for those who cannot handle standard treatments. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for elderly patients (≥75 years old with comorbidities or ≥80 years) newly diagnosed with CD20+ large cell lymphoma who can't handle standard anthracycline therapy. They should have a certain level of physical fitness (ECOG PS ≤2), measurable disease, and good organ function. Exclusions include major surgery within the last month, CNS tumors, active infections like hepatitis B/C or COVID-19, severe heart conditions, recent live vaccines, HIV positivity, other cancers or seizure disorders.

Inclusion Criteria

My cancer is at stage II, III, or IV according to the Ann Arbor classification.

My recent blood tests show my organs are functioning well.

Must have measurable disease as per Lugano criteria

Exclusion Criteria

I have been treated with specific therapies recently.

I have or had cancer types other than the one I'm seeking treatment for.

I have seizures and need medication for it, or I've had a seizure in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

Initial phase to assess safety of epcoritamab monotherapy and epcoritamab plus lenalidomide

4-8 weeks

Treatment

Participants receive either epcoritamab monotherapy or epcoritamab plus lenalidomide

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 days after last dose

What Are the Treatments Tested in This Trial?

Interventions

• Epcoritamab
• Lenalidomide

Trial Overview The study tests epcoritamab alone or combined with lenalidomide in treating Diffuse Large B-Cell Lymphoma in those unfit for anthracycline therapy. All participants receive treatment; they're randomly assigned to one of the two groups to compare effectiveness and safety.

How Is the Trial Designed?

Group I: Epcoritamab monotherapy Experimental Treatment 1 Intervention

Group II: Epcoritamab in combination with lenalidomide Experimental Treatment 2 Interventions

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

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, especially when combined with rituximab (the 'R(2)' regimen), shows enhanced efficacy in treating indolent B-cell and mantle cell lymphomas, even in patients resistant to rituximab, while maintaining a manageable safety profile.

The most common serious side effect is asymptomatic neutropenia, which can be managed through dose adjustments, and while immune-related symptoms like rash are more frequent with the R(2) regimen, they are generally low-grade and manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with lenalidomide alone or in combination with rituximab in indolent B-cell and mantle cell lymphomas. Ruan, J., Shah, B., Martin, P., et al.[2020]

The study determined that the maximum tolerated dose of docetaxel and carboplatin combined with lenalidomide is docetaxel 60 mg/m² and carboplatin AUC 6, with lenalidomide at 5 mg daily for 14 days in a 21-day cycle, showing manageable toxicity without treatment-related deaths.

Out of 14 patients with solid tumors, 5 achieved a partial response, particularly 5 out of 9 patients with non-small cell lung cancer, indicating that this combination therapy is active and warrants further investigation in phase II trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of three-weekly docetaxel, carboplatin and oral lenalidomide (Revlimid) in patients with advanced solid tumors. Kalmadi, S., Davis, M., Dowlati, A., et al.[2022]

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 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]

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 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 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]

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]

In a study of 33 patients with relapsed/refractory non-Hodgkin lymphoma, the GROC-Rev chemotherapy regimen followed by lenalidomide maintenance therapy resulted in a 61% overall response rate, with 39% achieving complete response (CR).

The treatment was generally well-tolerated, although some patients experienced significant adverse events like neutropenia and infections, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A New Salvage Regimen for Aggressive Lymphomas Based on Gemcitabine, Rituximab, and Oxaliplatin Followed by Lenalidomide (GROC-Rev). Cabanillas, F., Rivera, N., Acosta, M., et al.[2022]

Citations

1. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/438/501964/Subcutaneous-Epcoritamab-Plus-Lenalidomide-in

Subcutaneous Epcoritamab Plus Lenalidomide in Patients ... Single-agent epcoritamab has demonstrated deep and durable responses (overall response rate, 63%; complete responses, 40%) and a manageable ...

2. 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 ...

3. news.abbvie.com news.abbvie.com/2024-12-09-Two-Data-Analyses-From-Clinical-Trials-Show-Epcoritamab-DuoBody-R-CD3xCD20-Induces-Durable-Complete-Reponses-As-Monotherapy-and-Combination-Treatment-in-Patients-With-Diffuse-Large-B-Cell-Lymphoma

Two Data Analyses From Clinical Trials Show Epcoritamab ... Among complete responders, an estimated 83% remained in remission after two years. Separately, three-year follow-up results from the Phase 2 ...

4. onclive.com onclive.com/view/epcoritamab-plus-rituximab-and-lenalidomide-hits-both-primary-end-points-in-r-r-follicular-lymphoma

Epcoritamab Plus Rituximab and Lenalidomide Hits Both ... The epcoritamab, rituximab, and lenalidomide combination showed significant efficacy in relapsed/refractory follicular lymphoma, reducing death ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04663347

NCT04663347 | Safety and Efficacy Trial of Epcoritamab ... The purpose of this trial is to measure the safety and effectiveness of epcoritamab (EPKINLY™), either by itself or together with other therapies, ...

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

Safety and Efficacy of Epcoritamab in Relapsed, Refractory ... Conclusions. 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 ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04663347

NCT04663347 | Safety and Efficacy Trial of Epcoritamab ... The purpose of this trial is to measure the safety and effectiveness of epcoritamab (EPKINLY™), either by itself or together with other therapies, ...

8. 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 ... The median OS for epcoritamab was 7.8 months (95% CI, 6.0-13.0) and 9.7 months (95% CI, 6.8 months to not reached) for glofitamab. There were no ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10392166/

Epcoritamab-bysp (Epkinly) – A phenomenal breakthrough ... Epcoritamab-bysp has demonstrated a manageable safety profile in clinical trials, with adverse events consistent with those expected for ...

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

Epcoritamab in relapsed/refractory large B-cell lymphoma We report long-term efficacy and safety results in patients with LBCL (N = 157; 25.1-month median follow-up). As of April 21, 2023, overall ...