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

(EPCORE DLBCL-3 Trial)

Recruiting at 72 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

180 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to examine efficacy and safety of epcoritamab with and without lenalidomide in newly diagnosed elderly patients with Diffuse Large B-Cell Lymphoma (DLBCL) who cannot tolerate anthracycline therapy. Epcoritamab (also known as EPKINLY™, GEN3013 and DuoBody®-CD3xCD20) is an antibody that has already been tested in several clinical studies. All patients will receive active treatment. There is an equal chance of receiving epcoritamab or epcoritamab plus lenalidomide.

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.

What data supports the effectiveness of the drug lenalidomide for non-Hodgkin's lymphoma?

Lenalidomide has shown significant activity in treating non-Hodgkin's lymphoma, especially when combined with other drugs like rituximab, improving progression-free survival in patients with relapsed or refractory forms of the disease. ^{1 2 3 4 5}

Is the combination of Epcoritamab and Lenalidomide safe for treating Non-Hodgkin's Lymphoma?

Lenalidomide, used alone or with other drugs, generally has a manageable safety profile for treating various types of lymphoma. Common side effects include low white blood cell counts, which are usually managed with dose adjustments. Other side effects like fatigue and rash are typically mild and manageable. ^{1 5 6 7 8}

What makes the drug Epcoritamab +/- Lenalidomide unique for treating non-Hodgkin's lymphoma?

Epcoritamab combined with Lenalidomide is unique because it combines a novel bispecific antibody (Epcoritamab) with an immunomodulatory drug (Lenalidomide), potentially enhancing the immune system's ability to target and destroy lymphoma cells. This combination may offer a new approach for patients who have not responded to other treatments. ^{1 5 9 10 11}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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]

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, 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]

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]

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, 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 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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

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

2. England pubmed.ncbi.nlm.nih.gov

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

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

A New Salvage Regimen for Aggressive Lymphomas Based on Gemcitabine, Rituximab, and Oxaliplatin Followed by Lenalidomide (GROC-Rev). [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

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

6. England pubmed.ncbi.nlm.nih.gov

Clinical experience with lenalidomide alone or in combination with rituximab in indolent B-cell and mantle cell lymphomas. [2020]

7. Italy pubmed.ncbi.nlm.nih.gov

Efficacy and safety of lenalidomide in diffuse large B-cell lymphoma: a meta-analysis of randomized controlled trials. [2023]

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

Phase I trial of three-weekly docetaxel, carboplatin and oral lenalidomide (Revlimid) in patients with advanced solid tumors. [2022]

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

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

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

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

11. 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]