Epcoritamab + R2 for Follicular Lymphoma

(EPCORE FL-1 Trial)

Recruiting at 444 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)

549 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug combination to treat adults with a type of cancer called follicular lymphoma that has returned or resisted other treatments. The new drug, epcoritamab, is used with lenalidomide and rituximab to help the immune system fight the cancer. The study will check how safe and effective this treatment is.

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.

What data supports the idea that Epcoritamab + R2 for Follicular Lymphoma is an effective treatment?

The available research shows that the combination of lenalidomide and rituximab, which is part of the Epcoritamab + R2 treatment, has been effective for follicular lymphoma. In the AUGMENT trial, this combination significantly delayed the progression of the disease compared to a placebo with rituximab. This benefit was especially noted in patients with follicular lymphoma, including older patients. Additionally, the MAGNIFY trial showed that this combination was active in patients whose disease had returned or was resistant to rituximab. These studies suggest that Epcoritamab + R2 is a promising option for treating follicular lymphoma. ^{1 2 3 4 5}

What data supports the effectiveness of the drug combination Epcoritamab + R2 for Follicular Lymphoma?

Research shows that the combination of lenalidomide and rituximab, which are part of the R2 regimen, significantly improves progression-free survival in patients with follicular lymphoma. This combination has been effective in both previously treated and untreated cases, making it a promising option for managing this type of lymphoma. ^{1 2 3 4 5}

What safety data is available for the Epcoritamab + R2 treatment in follicular lymphoma?

The safety data for the R2 regimen (lenalidomide and rituximab) in follicular lymphoma shows that it has a manageable safety profile. Common adverse events include grade 3/4 neutropenia, rash, and gastrointestinal issues. These are generally predictable and manageable with dose adjustments and supportive care. The combination has been shown to improve efficacy over rituximab monotherapy, with acceptable toxicity levels. Hematologic adverse events like neutropenia are the most frequent, but they are typically managed by dose interruption and reduction. Nonhematologic toxicities such as fatigue are generally low-grade and manageable. The addition of lenalidomide to rituximab significantly improves response rates and progression-free survival, though it comes with higher, but manageable, toxicity. ^{1 6 7 8 9}

Is the combination of Epcoritamab, Lenalidomide, and Rituximab safe for treating follicular lymphoma?

The combination of Lenalidomide and Rituximab (R2) has been shown to have a manageable safety profile in treating follicular lymphoma, with common side effects including low white blood cell counts (neutropenia), skin rashes, and digestive issues. These side effects are generally predictable and can be managed with dose adjustments and supportive care. ^{1 6 7 8 9}

Is the drug Epcoritamab, Lenalidomide, Rituximab a promising treatment for Follicular Lymphoma?

Yes, the combination of Epcoritamab, Lenalidomide, and Rituximab is promising for treating Follicular Lymphoma. Lenalidomide and Rituximab have shown to significantly improve progression-free survival in patients, meaning they help keep the disease from getting worse for a longer time. This combination is especially beneficial for patients who have already been treated for Follicular Lymphoma, offering a new and effective option. ^{1 5 10 11 12}

What makes the drug Epcoritamab + R2 unique for treating follicular lymphoma?

The combination of Epcoritamab with Lenalidomide and Rituximab (R2) is unique because it combines a novel bispecific antibody (Epcoritamab) that targets two different proteins on cancer cells with an established immunomodulatory drug (Lenalidomide) and a monoclonal antibody (Rituximab), potentially enhancing the immune system's ability to fight follicular lymphoma more effectively than traditional treatments. ^{1 5 10 11 12}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

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]

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 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]

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]

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]

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 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]

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]

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 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]

References

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

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

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

How have outcomes for patients with follicular lymphoma changed with the addition of monoclonal antibodies? [2019]

3. 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]

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

Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance). [2022]

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

Antibody Therapy Maintenance in Follicular Lymphoma. [2021]

6. United States 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. [2021]

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

Lenalidomide plus rituximab can produce durable clinical responses in patients with relapsed or refractory, indolent non-Hodgkin lymphoma. [2018]

8. 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]

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

Short regimen of rituximab plus lenalidomide in follicular lymphoma patients in need of first-line therapy. [2021]

10. United States 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. [2016]

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

A phase 2 trial of extended induction epratuzumab and rituximab for previously untreated follicular lymphoma: CALGB 50701. [2021]

12. England 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. [2019]