Epcoritamab + R-CHOP for Diffuse Large B-Cell Lymphoma

(EPCORE DLBCL-2 Trial)

Not currently recruiting at 628 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Genmab

Must be taking: R-CHOP

Disqualifiers: Prior anti-lymphoma therapy, cardiovascular disease

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: 21-day cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for diffuse large B-cell lymphoma (DLBCL), a rare and aggressive cancer affecting certain white blood cells. Researchers aim to evaluate how epcoritamab, an investigational drug, performs when combined with the standard treatment known as R-CHOP, which includes multiple drugs administered orally and by injection. Participants will join one of two groups: one group will receive epcoritamab with R-CHOP, while the other will receive R-CHOP followed by rituximab. Individuals newly diagnosed with DLBCL and set to begin standard R-CHOP treatment might be suitable for this trial. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

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

The trial protocol does not specify if you need to stop your current medications. However, it does mention that participants should not have a history of prior systemic anti-lymphoma therapy for DLBCL, except for corticosteroids with or without vincristine during prephase treatment. It's best to discuss your current medications with the study doctors.

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

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study doctors to understand how your current medications might interact with the trial treatments.

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

Research shows that epcoritamab, when used alone, yields promising results and is generally safe. Studies found it was well-tolerated, with 63% of patients showing improvement and 39% having no detectable cancer in difficult-to-treat B-cell lymphoma. This indicates that most patients improved, and some had no signs of cancer remaining.

When combined with R-CHOP, a common chemotherapy mix for lymphoma, the treatment achieved high and lasting success rates. The side effects were mostly mild, suggesting the treatment is generally safe for individuals with high-risk diffuse large B-cell lymphoma.

R-CHOP is a standard treatment that includes drugs like rituximab, cyclophosphamide, and prednisone, which are familiar to doctors. It's widely used and has a known safety record. Adding epcoritamab enhances a treatment doctors already trust.

Overall, the evidence suggests this treatment is well-tolerated and potentially very effective. However, discussing with a healthcare provider is crucial to determine if joining a trial is the right choice. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Epcoritamab is unique because it introduces a novel approach to treating diffuse large B-cell lymphoma (DLBCL) by being a bispecific antibody that targets both CD3 and CD20 proteins on cancer cells, potentially enhancing the immune system's ability to attack the cancer. Unlike the standard R-CHOP regimen, which has been the backbone of DLBCL treatment, epcoritamab is administered subcutaneously, offering a different delivery method that might improve patient convenience and compliance. Researchers are excited about the potential of epcoritamab to work synergistically with the existing R-CHOP components, possibly leading to improved outcomes for patients with DLBCL.

What evidence suggests that this trial's treatments could be effective for diffuse large B-cell lymphoma?

In this trial, participants will receive either Epcoritamab combined with R-CHOP or R-CHOP followed by Rituximab. Research has shown that adding Epcoritamab to the standard treatment, R-CHOP, may effectively treat diffuse large B-cell lymphoma (DLBCL). In studies, 61% of patients who received Epcoritamab went into remission, with 38% achieving complete remission. Another study found a 64.3% overall response rate, with 47.6% of patients reaching a complete response. R-CHOP alone has been successful for many, and adding Epcoritamab appears to enhance its effectiveness. These findings suggest that combining Epcoritamab with R-CHOP could be a strong treatment option for DLBCL. ^{6 7 8 9 10}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

Adults with newly diagnosed CD20+ diffuse large B-cell lymphoma (DLBCL) who have not had prior systemic anti-lymphoma therapy, except certain steroids or vincristine for pre-treatment. Participants must have a specific level of disease severity (IPI score 2-5), be able to perform daily activities (ECOG score 0-2), and meet certain health criteria including heart function and measurable lesions.

Inclusion Criteria

Must have an IPI score of 2-5. The number of participants with IPI 2 will not exceed approximately 30% of the overall sample size

I can provide a recent tumor sample for the study.

I can perform daily activities with little to no assistance before starting R-CHOP treatment.

Exclusion Criteria

I have a serious heart condition.

I have had treatment for DLBCL, excluding certain steroids or palliative radiotherapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous epcoritamab combined with intravenous and oral R-CHOP or R-CHOP followed by rituximab in 21-day cycles

21-day cycles

Regular visits at an approved institution

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 46 months

Long-term follow-up

Participants are monitored for overall survival and event-free survival

Up to approximately 76 months

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Doxorubicin
• Epcoritamab
• Prednisone
• Rituximab
• Vincristine

Trial Overview The trial is testing the effectiveness of Epcoritamab combined with R-CHOP chemotherapy compared to standard R-CHOP alone in treating DLBCL. Patients are randomly assigned to one of two groups: one receiving subcutaneous Epcoritamab plus R-CHOP, the other receiving just R-CHOP followed by Rituximab, both in cycles lasting 21 days.

How Is the Trial Designed?

Group I: R-CHOP and Rituximab Experimental Treatment 5 Interventions

Participants will receive intravenous rituximab, cyclophosphamide, doxorubixin hydrochloride, vincristine and oral prednisone (R-CHOP) followed by intravenous rituximab in 21-day cycles.

Group II: Epcoritamab and R-CHOP Experimental Treatment 6 Interventions

Participants will receive subcutaneous epcoritamab combined with intravenous rituximab, cyclophosphamide, doxorubixin hydrochloride, vincristine and oral prednisone (R-CHOP) followed by epcoritamab in 21-day cycles.

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

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 a study involving 946 patients with non-Hodgkin's lymphoma, the use of nonpeghylated liposomal doxorubicin (NPLD) as a substitute for standard doxorubicin resulted in a high complete remission rate of 72.6%, demonstrating its efficacy in treating this population.

The incidence of major cardiotoxic events was relatively low at 5%, indicating that NPLD significantly reduces the risk of heart-related complications, making it a safer option for elderly patients and those with pre-existing cardiac conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonpeghylated liposomal doxorubicin combination regimen (R-COMP) for the treatment of lymphoma patients with advanced age or cardiac comorbidity. Rigacci, L., Annibali, O., Kovalchuk, S., et al.[2020]

In a study of 397 newly diagnosed diffuse large B-cell lymphoma patients treated with R-CHOP, non-neutropenic fever (NNF) occurred in 9.8% of patients, primarily after the third cycle, with interstitial pneumonitis being the most common cause.

NNF was associated with a higher mortality rate of 10.3% compared to febrile neutropenia (FN), which had a mortality rate of only 1.3%, highlighting the need for careful monitoring and management of febrile complications during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Significance of Non-neutropenic Fever in the Management of Diffuse Large B-Cell Lymphoma Patients Treated with Rituximab-CHOP: Comparison with Febrile Neutropenia and Risk Factor Analysis. Park, S., Kang, CI., Chung, DR., et al.[2018]

In a study of 112 patients under 65 years old with diffuse large B-cell lymphoma, the combination of rituximab and high-dose sequential chemotherapy led to an impressive 80% clinical remission rate, demonstrating its efficacy in treating this aggressive cancer.

At a median follow-up of 48 months, 78% of patients remained alive and 73% were in continuous remission, indicating that this treatment significantly improves life expectancy compared to conventional chemotherapy for younger patients with higher risk scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged survival in poor-risk diffuse large B-cell lymphoma following front-line treatment with rituximab-supplemented, early-intensified chemotherapy with multiple autologous hematopoietic stem cell support: a multicenter study by GITIL (Gruppo Italiano Terapie Innovative nei Linfomi). Tarella, C., Zanni, M., Di Nicola, M., et al.[2022]

The R-CHOP regimen, which includes rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, is a standard first-line treatment for diffuse large B-cell lymphoma, highlighting its importance in oncology.

Nursing implications of administering R-CHOP are significant, as the combination of these drugs requires careful monitoring for side effects and patient management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nursing Alchemy: Transforming R-CHOP Information Into Essentials. Sakowski, AK., Patel, PR.[2023]

In a study of 180 patients with aggressive non-Hodgkin's lymphoma, the use of dexrazoxane significantly reduced the risk of cardiac events and congestive heart failure (CHF) during treatment with the CHOP/R-CHOP regimen, with a 5-year cumulative risk of cardiac events dropping from 29% to 8% after its introduction.

Younger patients (under 60 years) also showed a lower risk of cardiac events, indicating that both dexrazoxane and age are important factors in protecting against the cardiotoxic effects of chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and risk-factors of CHOP/R-CHOP-related cardiotoxicity in patients with aggressive non-Hodgkin's lymphoma. Limat, S., Daguindau, E., Cahn, JY., et al.[2022]

In a retrospective analysis of 371 high-risk DLBCL patients, adding rituximab to standard chemotherapy (R-CHOP) significantly improved overall response rates (ORR) from 76.7% to 95.6% (P <0.05).

R-CHOP with rituximab also enhanced 5-year overall survival (OS) and progression-free survival (PFS) in both younger and older patients, with younger patients showing OS of 42% vs 38% and PFS of 46% vs 27%, and older patients showing OS of 82% vs 52% and PFS of 67% vs 45% (all P <0.05).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of rituximab in the first-line therapy of high-risk diffuse large B-cell lymphoma: a retrospective analysis by the Polish Lymphoma Research Group. Jurczak, W., Ochrem, B., Giza, A., et al.[2019]

In a study involving 166 patients with aggressive B-cell lymphoma, the addition of radiotherapy (RT) to the standard R-CHOP treatment significantly improved event-free survival (EFS) for those with bulky disease, indicating that RT is beneficial for this patient group.

Patients who did not receive RT had a higher risk of disease progression and lower overall survival rates, suggesting that RT effectively mitigates the risks associated with bulky disease in elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of radiotherapy to bulky disease in elderly patients with aggressive B-cell lymphoma. Held, G., Murawski, N., Ziepert, M., et al.[2022]

The medication instruction sheet (MIS) developed for patients receiving R-CHOP therapy effectively predicted 71% of adverse drug reactions (ADRs) during the treatment period, demonstrating its usefulness in managing these reactions.

The MIS accurately matched the onset timing of infusion reactions and peripheral neuropathy, although its effectiveness was lower for predicting thrombocytopenia-related ADRs, indicating areas for improvement in monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Medication Instruction Sheets for Patients Undergoing R-CHOP Therapy in Non-Hodgkin's Lymphoma. Uchida, M., Kawai, R., Hisamitsu, R., et al.[2022]

In a study of 50 patients treated with R-CHOP-14 for aggressive B-cell lymphoma, 82% achieved a complete or improved response, indicating high efficacy of this treatment regimen.

Despite its effectiveness, R-CHOP-14 was associated with significant toxicities, including grade 3-4 neutropenia in 32% of patients and peripheral neuropathy in 45%, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with biweekly CHOP plus rituximab chemoimmunotherapy for the treatment of aggressive B-cell non-Hodgkin lymphoma. Aguiar Bujanda, D., Aguiar Morales, J., Bohn Sarmiento, U., et al.[2021]

The CEOP chemotherapy regimen, which substitutes epirubicin for doxorubicin, demonstrated a high efficacy with a complete remission rate of 64.3% in 186 patients with intermediate- or high-grade non-Hodgkin lymphoma, particularly benefiting elderly patients.

Long-term follow-up showed that 79.8% of patients who achieved complete remission remained disease-free at a median of 86.9 months, indicating that CEOP is not only effective but also well-tolerated, with no deaths from cardiac toxicity reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of patients with intermediate or high-grade non-Hodgkin lymphoma treated with a combination of cyclophosphamide, epirubicin, vincristine, and prednisone. Rossini, F., Terruzzi, E., Perego, D., et al.[2015]

In a study of 40 patients with low-grade or follicular B-cell non-Hodgkin's lymphoma, the combination of Rituxan (Rituximab) and CHOP chemotherapy resulted in a high overall response rate of 95%, with 55% achieving complete remission.

The combination therapy showed promising safety, with common side effects being manageable, and it also indicated potential for clearing minimal residual disease, as evidenced by the conversion of the bcl-2 translocation from positive to negative in several patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. Czuczman, MS., Grillo-López, AJ., White, CA., et al.[2022]

In a study of 435 patients with diffuse large B-cell lymphoma (DLBCL), the addition of rituximab to CHOP chemotherapy (R-CHOP) was associated with a reduced risk of central nervous system (CNS) relapse, showing a trend of 6.4% risk in R-CHOP patients compared to 9.7% in those treated with CHOP.

Rituximab significantly lowered the risk of CNS relapse (hazard ratio 0.45) and this benefit was even greater for patients who achieved a complete response (hazard ratio 0.18), indicating that R-CHOP is particularly effective in preventing CNS involvement in DLBCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and risk factors for central nervous system relapse in patients with diffuse large B-cell lymphoma: the impact of the addition of rituximab to CHOP chemotherapy. Villa, D., Connors, JM., Shenkier, TN., et al.[2022]

In a study of 80 patients with high-risk diffuse large B cell lymphoma (DLBCL), the DA.R-EPOCH treatment showed comparable progression-free and overall survival rates to the standard R-CHOP treatment, indicating similar efficacy.

However, DA.R-EPOCH was associated with significantly higher treatment costs, averaging around USD 106,940 compared to USD 58,509 for R-CHOP, highlighting a trade-off between cost and treatment choice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost Analysis of R-CHOP Versus Dose-Adjusted R-EPOCH in Treatment of Diffuse Large B-Cell Lymphoma with High-Risk Features. Dholaria, B., Vanegas, YAM., Diehl, N., et al.[2021]

In a study of 134 patients with diffuse large B-cell lymphoma (DLBCL) involving the testis, the addition of rituximab to standard chemotherapy (R-CHOP) significantly improved progression-free survival and overall survival, with hazard ratios of 0.42 and 0.39 respectively, indicating a strong protective effect.

Despite the benefits of rituximab in reducing lymphoma recurrence, the risk of central nervous system (CNS) relapse remained high, suggesting that additional strategies for CNS prophylaxis are necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diffuse large B-cell lymphoma with testicular involvement: outcome and risk of CNS relapse in the rituximab era. Kridel, R., Telio, D., Villa, D., et al.[2017]

In a study of 582 patients with diffuse large B-cell lymphoma (DLBCL) treated in Germany, both R-CHOP-14 and R-CHOP-21 regimens showed similar overall survival rates at 3 years, with 84% for R-CHOP-14 and 84% for R-CHOP-21.

The findings confirm previous randomized clinical trials that indicated no superiority of the dose-dense R-CHOP-14 over the standard R-CHOP-21, supporting the use of either regimen in routine clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Similar effectiveness of R-CHOP-14 and -21 in diffuse large B-cell lymphoma-data from the prospective German Tumour Registry Lymphatic Neoplasms. Knauf, W., Abenhardt, W., Mohm, J., et al.[2020]

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. 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/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 EPCORE® NHL-6 trial results are notable, as current bispecific antibody treatments for relapsed and refractory diffuse large B-cell ...

4. 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 ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39322711/

Epcoritamab in relapsed/refractory large B-cell lymphoma As of April 21, 2023, overall response rate was 63.1% and complete response (CR) rate was 40.1%. Estimated 24-month progression-free survival ( ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05578976

NCT05578976 | A Study to Evaluate Change in Disease ... The purpose of this study is to assess the change in disease activity of epcoritamab when combined with intravenous and oral rituximab, cyclophosphamide, ...

7. asco.org asco.org/abstracts-presentations/ABSTRACT417108

Phase 3 trial of subcutaneous epcoritamab + R-CHOP ... Epcoritamab monotherapy demonstrated deep and durable responses (overall response rate [ORR], 63%; complete response rate, 39%) and was generally well tolerated ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9430177/

P1214: SUBCUTANEOUS EPCORITAMAB + R-CHOP ... Epcoritamab is a subcutaneously administered, well-tolerated, bispecific antibody with single-agent antitumor activity in relapsed/refractory (R/R) aggressive B ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265023013198

ABCL-429 Epcoritamab + R-CHOP in Patients With ... Epcoritamab SC + R-CHOP induces high and durable CMR rates with a manageable safety profile in 1L high-risk DLBCL, including double-hit/triple-hit.

10. 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, ...