Epcoritamab + R2 for Follicular Lymphoma

(EPCORE FL-1 Trial)

Not currently recruiting at 527 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Genmab

Must be taking: Rituximab, Lenalidomide

Must not be taking: Lenalidomide

Disqualifiers: 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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 cycles (approximately 48 weeks)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates a new treatment for follicular lymphoma, a type of blood cancer affecting white blood cells that often recurs after standard treatments. Researchers aim to determine if combining the investigational drug epcoritamab (also known as Epkinly or Tepkinly) with lenalidomide and rituximab (R2) is safe and effective for patients whose cancer has returned or not responded to earlier treatments. Participants will be divided into groups to receive different treatment combinations. This trial may suit adults with follicular lymphoma that has relapsed or is resistant to previous treatments, including an anti-CD20 drug combined with chemotherapy. Regular hospital or clinic visits will be necessary for medical assessments and monitoring. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot have taken lenalidomide within 12 months before joining the trial.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, if you have taken lenalidomide in the past 12 months, you cannot participate.

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

Research has shown that combining epcoritamab with lenalidomide and rituximab (R2) may be effective for individuals with relapsed or refractory follicular lymphoma. Many patients experienced significant and lasting improvements with this combination. However, awareness of possible side effects is important.

Earlier studies identified the most common side effects of the epcoritamab combination as injection site reactions, fatigue, and upper respiratory infections. Some patients also experienced cytokine release syndrome (CRS), which can cause fever and fatigue. These side effects were generally manageable.

Epcoritamab remains under study and is not yet approved for treating follicular lymphoma. In contrast, lenalidomide and rituximab are approved and have well-known safety records. Participants should discuss potential risks and benefits with their doctors to make an informed decision about joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because Epcoritamab, a bispecific antibody, brings a novel approach to treating follicular lymphoma. Unlike traditional options like chemotherapy or standard immunotherapy, Epcoritamab targets both CD3 on T-cells and CD20 on B-cells, which may enhance the immune system’s ability to attack cancer cells directly. Additionally, the combination of Epcoritamab with Lenalidomide and Rituximab (R2) might offer a synergistic effect, potentially leading to more effective treatment outcomes. This multi-pronged strategy could provide a new avenue for patients who haven't responded well to existing therapies.

What evidence suggests that this trial's treatments could be effective for follicular lymphoma?

Research has shown that combining epcoritamab with lenalidomide and rituximab (R2) holds promise for treating follicular lymphoma (FL). In this trial, participants will receive varying doses of epcoritamab with R2, or R2 alone. A study of 127 patients with this cancer found that 82% went into remission, significantly improving their condition, and 60% achieved complete remission, with no detectable cancer after treatment. Epcoritamab has also demonstrated long-lasting effects. These findings suggest that adding epcoritamab to the R2 treatment could benefit people with FL who have not responded to other treatments. ^{3 6 7 8 9}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

Adults with relapsed or refractory Follicular Lymphoma who've had prior treatments including an anti-CD20 monoclonal antibody can join. They need a positive PET scan showing the disease and at least one measurable lesion. Participants should be able to perform daily activities (ECOG score 0-2) and have not been treated with lenalidomide in the past year.

Inclusion Criteria

My doctor has approved me for R2 treatment.

My lymphoma is confirmed to be of a type that has not become more aggressive and tests positive for CD20.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

I have been treated with lenalidomide in the last 12 months.

My condition did not improve with lenalidomide treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive R2 (rituximab and lenalidomide) alone or in combination with epcoritamab for up to 12 cycles, each cycle being 28 days

12 cycles (approximately 48 weeks)

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 8 years

What Are the Treatments Tested in This Trial?

Interventions

• Epcoritamab
• Lenalidomide
• Rituximab

Trial Overview The trial is testing Epcoritamab combined with Rituximab and Lenalidomide (R2) for safety and effectiveness against Follicular Lymphoma. Patients are divided into groups receiving different treatments, including R2 alone or with Epcoritamab, over multiple cycles lasting 28 days each.

How Is the Trial Designed?

Group I: Epcoritamab Dose B in Combination With R2 Experimental Treatment 3 Interventions

Participants will receive epcoritamab Dose B in combination with lenalidomide and rituximab (R2) for 12 cycles (each cycle is 28 days). Enrollment is closed for this arm.

Group II: Epcoritamab Dose A in Combination With R2 Experimental Treatment 3 Interventions

Participants will receive epcoritamab Dose A in combination with lenalidomide and rituximab (R2) for 12 cycles (each cycle is 28 days).

Group III: Lenalidomide and Rituximab (R2) Active Control 2 Interventions

Participants will receive lenalidomide and rituximab (R2) for 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

The combination of rituximab and lenalidomide (R2) significantly improves treatment efficacy for recurrent non-Hodgkin lymphoma compared to rituximab alone, leading to its approval for use in previously treated patients with follicular and marginal zone lymphoma.

R2 has a manageable safety profile, with common adverse events including grade 3/4 neutropenia, skin rashes, and gastrointestinal issues, indicating that while it is effective, careful monitoring and management of side effects are necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Adverse Events From the Combination of Rituximab and Lenalidomide in the Treatment of Patients With Follicular and Low-Grade Non-Hodgkin Lymphoma. Cheson, BD., Morschhauser, F., Martin, P.[2021]

The combination of lenalidomide and rituximab (LR) showed a significantly higher overall response rate (76%) compared to lenalidomide alone (53%) in patients with recurrent follicular lymphoma, indicating that LR is more effective in treating this condition.

Both treatment regimens had similar rates of severe adverse events (grade 3 to 4), but lenalidomide alone resulted in more treatment failures, suggesting that LR may provide a better balance of efficacy and tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance). Leonard, JP., Jung, SH., Johnson, J., et al.[2022]

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]

Rituximab maintenance therapy significantly improves progression-free survival in patients with follicular lymphoma after initial treatment, regardless of tumor burden or patient characteristics, based on multiple randomized studies.

Key questions remain about the best administration schedule, duration of treatment, and the cost-effectiveness of rituximab maintenance, especially for patients previously treated with bendamustine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody Therapy Maintenance in Follicular Lymphoma. Golfier, C., Salles, G.[2021]

In a phase 2 trial involving 80 patients with untreated high burden follicular lymphoma, the combination of lenalidomide and R-CHOP (R2-CHOP) resulted in a high complete response rate of 74% after six treatment cycles, indicating strong anti-cancer activity.

The treatment was generally safe, with the most common side effect being grade 4 neutropenia in 65% of patients, but no treatment-related deaths were reported, suggesting an acceptable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with R-CHOP (R2-CHOP) as first-line treatment of patients with high tumour burden follicular lymphoma: a single-arm, open-label, phase 2 study. Tilly, H., Morschhauser, F., Casasnovas, O., et al.[2019]

In the SAKK 35/10 phase 2 trial involving 154 untreated follicular lymphoma patients, the combination of rituximab and lenalidomide resulted in a significantly higher complete response rate at 6 months (36% vs 25% for rituximab alone).

The combination therapy also led to longer progression-free survival and time to next treatment, although it was associated with higher rates of severe toxicity (56% vs 22%), primarily due to neutropenia, indicating that while more effective, the combination requires careful management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short regimen of rituximab plus lenalidomide in follicular lymphoma patients in need of first-line therapy. Zucca, E., Rondeau, S., Vanazzi, A., et al.[2021]

The use of the anti-CD20 monoclonal antibody rituximab has significantly improved survival rates in patients with follicular lymphoma (FL), especially when used in combination with chemotherapy for both induction and maintenance therapy.

Radioimmunotherapy (RIT) using radiolabelled anti-CD20 mAbs, such as (90)Y Ibritumomab tiuxetan and (131)I Tositumomab, has shown high response rates and durable remissions, particularly when used as consolidation therapy after initial treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How have outcomes for patients with follicular lymphoma changed with the addition of monoclonal antibodies? Illidge, T., Chan, 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]

The combination of epratuzumab and rituximab was well-tolerated in 59 untreated patients with follicular lymphoma, showing a high response rate of 88.2%, with 42.4% achieving complete responses.

At a 3-year follow-up, 60% of patients remained in remission, indicating that this non-chemotherapy approach can provide effective long-term outcomes similar to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 trial of extended induction epratuzumab and rituximab for previously untreated follicular lymphoma: CALGB 50701. Grant, BW., Jung, SH., Johnson, JL., et al.[2021]

In a phase II study involving 30 patients with relapsed/refractory indolent non-Hodgkin lymphoma, the combination of lenalidomide and rituximab achieved a high overall response rate of 74%, with 44% of patients experiencing complete responses.

The treatment demonstrated a median progression-free survival of 12.4 months, and while there were some significant adverse events like neutropenia and lymphopenia, the overall toxicity was considered acceptable, indicating a promising safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide plus rituximab can produce durable clinical responses in patients with relapsed or refractory, indolent non-Hodgkin lymphoma. Tuscano, JM., Dutia, M., Chee, K., et al.[2018]

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]

In a study of 60 patients with symptomatic or bulky follicular lymphoma, a combination of short-course chemoimmunotherapy (CHOP-R) followed by radioimmunotherapy (RIT) led to a significant increase in complete response (CR) rates, from 40% after CHOP-R to 82% after RIT, as assessed by imaging.

The study found that patients who did not achieve a complete metabolic response on PET imaging after CHOP-R had a higher risk of relapse, highlighting the importance of early PET assessment in predicting treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma. Jacobs, SA., Swerdlow, SH., Kant, J., et al.[2016]

Citations

1. epkinlyhcp.com epkinlyhcp.com/fl/clinical-trial-results

FL Clinical Trial Results - EPKINLY® (epcoritamab-bysp) ... Even with a high enrollment of patients with difficult-to-treat disease,* 60% CR was observed in EPCORE® NHL-11-4. 82% of patients had a response (n equals ...

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

Clinical Trial Results - EPKINLY® (epcoritamab-bysp) FL: In a clinical study of 127 patients receiving EPKINLY, 82% (104 patients) achieved remission: complete remission in 60% (76 patients) and partial remission ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12296760/

3-year follow-up from the EPCORE NHL-3 trial With > 3 years of follow-up, epcoritamab treatment has consistently shown durable responses and high rates of MRD negativity in Japanese ...

4. 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, ...

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. 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 ... Epcoritamab plus rituximab and lenalidomide met the dual primary end points of the EPCORE FL-1 in relapsed/refractory follicular lymphoma.

7. clinicaltrials.gov clinicaltrials.gov/show/NCT06191744

NCT06191744 | Study of Subcutaneous Epcoritamab in ... This study will assess how safe and effective epcoritamab is in combination with lenalidomide and rituximab (R2) in treating adult participants ...

8. ashpublications.org ashpublications.org/blood/article/doi/10.1182/blood.2025029909/547148/Fixed-Duration-Epcoritamab-Plus-R2-Drives

Fixed-Duration Epcoritamab Plus R2 Drives Favorable ... Key Points. Fixed-duration epcoritamab plus R2 showed deep, durable responses with favorable long-term outcomes in R/R FL regardless of risk ...

9. ir.genmab.com ir.genmab.com/news-releases/news-release-details/genmab-announces-phase-3-epcorer-fl-1-clinical-trial-met-dual

Genmab Announces Phase 3 EPCORE® FL-1 Clinical ... The safety and efficacy of epcoritamab in combination with R2 in R/R FL is currently being evaluated in clinical trials and is not approved or ...