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

(EPCORE DLBCL-2 Trial)

Recruiting at 562 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: Genmab

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests a new drug called epcoritamab combined with a mix of cancer-fighting drugs in adults with a rare type of aggressive cancer called DLBCL. Epcoritamab helps the immune system attack cancer cells, while the other drugs work together to kill them. This combination has been used as the standard treatment for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) for many years.

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.

What data supports the idea that Epcoritamab + R-CHOP for Diffuse Large B-Cell Lymphoma is an effective treatment?

The available research shows that adding rituximab to the R-CHOP treatment improves outcomes for patients with Diffuse Large B-Cell Lymphoma. For example, one study found that patients treated with R-CHOP had better progression-free survival compared to those who did not receive rituximab. Another study compared R-CHOP to a more intensive treatment called DA.R-EPOCH and found that R-CHOP had similar outcomes but was less expensive. These findings suggest that R-CHOP, which includes rituximab, is an effective treatment option. However, there is no specific data provided on the combination of Epcoritamab with R-CHOP, so its effectiveness cannot be directly assessed from the available information. ^{1 2 3 4 5}

What safety data exists for Epcoritamab + R-CHOP treatment in Diffuse Large B-Cell Lymphoma?

The safety data for the R-CHOP regimen, which includes rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, highlights several key points. Doxorubicin is known for its cardiotoxicity, especially in elderly patients or those with pre-existing cardiac conditions. Studies have shown that substituting doxorubicin with liposomal doxorubicin can reduce cardiotoxicity. The R-CHOP regimen is associated with severe adverse drug reactions, and medication instruction sheets have been developed to manage these. Cardiotoxicity remains a significant concern, with factors like age and cardiac history influencing risk. Epcoritamab, a newer addition, may have its own safety profile, but specific data on its combination with R-CHOP is not detailed in the provided research. ^{6 7 8 9 10}

Is the drug combination Epcoritamab + R-CHOP promising for treating Diffuse Large B-Cell Lymphoma?

The R-CHOP drug combination is a standard and effective first-line treatment for Diffuse Large B-Cell Lymphoma. Adding Epcoritamab, a new drug, could potentially enhance its effectiveness, making it a promising option. ^{11 12 13 14 15}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

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.

Treatment Details

Interventions

• Cyclophosphamide (Alkylating agents)
• Doxorubicin (Anti-tumor antibiotic)
• Epcoritamab (Monoclonal Antibodies)
• Prednisone (Corticosteroid)
• Rituximab (Monoclonal Antibodies)
• Vincristine (Vinca alkaloids)

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.

Participant Groups

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 Canada, Japan for the following indications:

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

Findings from Research

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 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]

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 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]

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]

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 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]

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 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 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]

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 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]

References

1. England 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). [2022]

2. England 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. [2022]

3. Italy pubmed.ncbi.nlm.nih.gov

Clinical experience with biweekly CHOP plus rituximab chemoimmunotherapy for the treatment of aggressive B-cell non-Hodgkin lymphoma. [2021]

4. England 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. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Diffuse large B-cell lymphoma with testicular involvement: outcome and risk of CNS relapse in the rituximab era. [2017]

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

Nonpeghylated liposomal doxorubicin combination regimen (R-COMP) for the treatment of lymphoma patients with advanced age or cardiac comorbidity. [2020]

7. United States 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. [2015]

8. United States 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. [2022]

9. Greece pubmed.ncbi.nlm.nih.gov

Evaluation of Medication Instruction Sheets for Patients Undergoing R-CHOP Therapy in Non-Hodgkin's Lymphoma. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Incidence and risk-factors of CHOP/R-CHOP-related cardiotoxicity in patients with aggressive non-Hodgkin's lymphoma. [2022]

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

Nursing Alchemy: Transforming R-CHOP Information Into Essentials. [2023]

12. Poland 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. [2019]

13. England 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. [2020]

14. Korea (South) 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. [2018]

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

Role of radiotherapy to bulky disease in elderly patients with aggressive B-cell lymphoma. [2022]