The Overview
AbbVie and Genmab announced positive topline results from the Phase 3 EPCORE DLBCL-2 trial, evaluating fixed treatment duration epcoritamab in combination with R-CHOP against R-CHOP alone in newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients with an International Prognostic Index (IPI) score of 2 to 5. The study demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS), reducing the risk of disease progression or death by 51% (HR 0.49 [95% CI 0.36, 0.67]; p-value < 0.0001). The safety profile of the combination was generally well tolerated and consistent with previously reported data. Based on these results, the companies will engage global regulatory authorities.
Knolens Analysis
At a Glance
| Indication | Diffuse Large B-Cell Lymphoma |
| Drug | epcoritamab and R-CHOP |
| Mechanism of Action | T-cell engaging bispecific antibody |
| Company | AbbVie |
| Trial Phase | Phase 3 |
| Trial Acronym | EPCORE DLBCL-2 |
| NCT ID | NCT05578976 |
| Category | Clinical Trial Event |
| Sub Category | Topline Results Positive |
| Therapeutic Area | Oncology |
| Primary Endpoint | PFS in participants with an International Prognostic Index (IPI) of 3-5 |
| Key Secondary Endpoint | PFS in total participants (IPI score of 2-5) |
| Risk Reduction (IPI 2-5) | 51% (HR 0.49 [95% CI 0.36, 0.67]; p-value < 0.0001) |
| Comparator Arm | R-CHOP alone |
| Patient Population Details | Newly diagnosed DLBCL patients with an International Prognostic Index (IPI) score of 2 to 5 |
| Regulatory Action | Engage global regulatory authorities |
| Co-development Partner | Genmab |
| Administration Route | Subcutaneously |
| Randomization Ratio | 2:1 |
| Interim Analysis Outcome | Independent Data Monitoring Committee (IDMC) recommended unblinding the study |
Epcoritamab Plus R-CHOP Improves PFS in Newly Diagnosed DLBCL
AbbVie and Genmab announced positive topline results from the Phase 3 EPCORE DLBCL-2 trial, evaluating fixed treatment duration epcoritamab in combination with R-CHOP against R-CHOP alone in newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients with an International Prognostic Index (IPI) score of 2 to 5. The study demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS), reducing the risk of disease progression or death by 51% (HR 0.49 [95% CI 0.36, 0.67]; p-value < 0.0001). The safety profile of the combination was generally well tolerated and consistent with previously reported data. Based on these results, the companies will engage global regulatory authorities.
- The EPCORE DLBCL-2 trial is the first Phase 3 study of a bispecific antibody combination to demonstrate a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in frontline diagnosed DLBCL patients with an IPI score of 2 to 5. This included a 51% reduction in the risk of disease progression or death (HR 0.49 [95% CI 0.36, 0.67]; p-value < 0.0001).
- These positive topline results suggest that epcoritamab combined with R-CHOP could offer a potential new standard of care in newly diagnosed DLBCL patients. Experts believe these findings have the potential to reshape the frontline treatment landscape and mark an important step forward in bringing the opportunity of cure to more patients.
- The safety profile of epcoritamab when administered in combination with R-CHOP was generally well tolerated and consistent with the previously reported safety profiles of the individual agents. Following the first planned efficacy interim analysis, the Independent Data Monitoring Committee (IDMC) recommended unblinding the study, and AbbVie and Genmab will engage global regulatory authorities to determine next steps.
Frequently Asked Questions
Is R-CHOP an aggressive chemo?
R-CHOP is considered an aggressive chemotherapy regimen due to its multi-drug nature and the potency of its components. It combines the monoclonal antibody rituximab with four cytotoxic agents: cyclophosphamide, doxorubicin, vincristine, and prednisone. While highly effective and often curative for diffuse large B-cell lymphoma, its intensity is associated with a significant toxicity profile requiring careful patient management and supportive care.
Is epcoritamab better than chemo for lymphoma?
Epcoritamab is approved for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy, a setting where traditional chemotherapy options often have limited efficacy. In this heavily pretreated population, epcoritamab has demonstrated durable responses, offering a new mechanism of action compared to conventional chemotherapy. While direct head-to-head superiority over all chemotherapy regimens across all lymphoma settings is not established, epcoritamab provides a significant therapeutic advantage for patients who have failed prior chemoimmunotherapy.
What is the newest treatment for diffuse large B-cell lymphoma?
The newest treatments for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) are the CD20xCD3 bispecific T-cell engagers, glofitamab (Columvi) and epcoritamab (Epkinly). Both were approved in May and June 2023, respectively, for adult patients who have received two or more prior lines of systemic therapy. These off-the-shelf antibodies offer a novel mechanism of action for patients with difficult-to-treat R/R DLBCL.
What is the 5-year survival rate for patients with DLBCL?
The 5-year overall survival rate for patients with diffuse large B-cell lymphoma (DLBCL) is approximately 60-70%. This rate can vary significantly based on factors such as disease stage, patient age, and International Prognostic Index (IPI) score.
What is the standard of care for DLBCL?
R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) remains the foundational first-line standard of care for most patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). For relapsed or refractory DLBCL, autologous stem cell transplant (ASCT) following salvage chemotherapy is a standard for eligible patients. CAR T-cell therapies (e.g., axicabtagene ciloleucel, tisagenlecleucel, lisocabtagene maraleucel) have become a critical option for patients who relapse after two or more lines of therapy, and increasingly in earlier lines for high-risk patients. Other approved options for relapsed/refractory disease include tafasitamab plus lenalidomide and polatuzumab vedotin plus bendamustine and rituximab.
How quickly does diffuse large B-cell lymphoma spread?
Diffuse large B-cell lymphoma (DLBCL) is an aggressive, fast-growing non-Hodgkin lymphoma. It typically spreads rapidly, often disseminating from its primary site to other lymph nodes, bone marrow, spleen, liver, and extranodal tissues within weeks to months if untreated. This rapid progression underscores the urgency for timely diagnosis and initiation of systemic therapy.
What are the treatment guidelines for diffuse large B-cell lymphoma?
Standard first-line treatment for most newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). For high-risk or specific subtypes, dose-adjusted R-EPOCH or other intensified regimens may be considered. Relapsed or refractory DLBCL often involves salvage chemotherapy followed by autologous stem cell transplant (ASCT) for eligible patients, or CAR T-cell therapy for those who fail two or more lines of systemic therapy. Emerging therapies and clinical trials also play a crucial role in treatment decisions for advanced or difficult-to-treat cases.
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