Epcoritamab, a bispecific antibody, has demonstrated promising results in two clinical trials for diffuse large B-cell lymphoma (DLBCL) and large B-cell lymphoma (LBCL). The data suggest that epcoritamab, as both a monotherapy and in combination with standard treatments, induces durable responses in patients with these aggressive lymphomas.
EPCORE NHL-2 Trial: First-Line DLBCL
The EPCORE NHL-2 trial evaluated epcoritamab in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in 46 evaluable patients with high-risk DLBCL, characterized by International Prognostic Index (IPI) scores of 3 to 5. These scores are associated with poor long-term outcomes. The study revealed that 35% of patients had bulky disease (>10 cm), and 21% had double-hit/triple-hit DLBCL, aggressive subtypes driven by significant genetic mutations.
Lorenzo Falchi, M.D., Lymphoma Specialist, Memorial Sloan Kettering Cancer Center, noted, "More first-line treatments for diffuse large B-cell lymphoma are needed, especially for patients with aggressive disease markers that may impact the efficacy of current standard first-line therapies. The durable responses observed in the study suggest significant potential for this first-line epcoritamab-based combination."
Key findings from the trial include:
- 91% of patients achieved minimal residual disease (MRD) negativity in blood samples (n=33), indicating no detectable disease as defined by ctDNA.
- The most common treatment-emergent adverse events (TEAEs) were neutropenia (70%), anemia (69%), cytokine release syndrome (CRS 60%), fatigue (49%), and nausea (47%).
- The majority of CRS events were low grade (45% Grade 1, 11% Grade 2, 4% Grade 3), occurring mainly after the first full dose, and all cases resolved without leading to discontinuation.
EPCORE NHL-1 Trial: Third-Line LBCL
The EPCORE NHL-1 trial assessed epcoritamab monotherapy in 157 patients with relapsed or refractory LBCL after two or more prior lines of therapy. Three-year follow-up results demonstrated that epcoritamab continues to provide durable responses in this challenging-to-treat population.
Key results from the trial include:
- An overall response rate (ORR) of 59% and a complete response (CR) rate of 41%.
- Median duration of response was 20.8 months (95% CI, 13.0-32.0), and median duration of CR was 36.1 months (95% CI, 20.2 to not reached).
- MRD analysis showed that 45.4% of patients achieved MRD negativity.
- The most common TEAEs were CRS (51%; 32% Grade 1, 16% Grade 2, 3% Grade 3), fatigue (25%), and pyrexia (25%).
Epcoritamab: A Bispecific Antibody
Epcoritamab, co-developed by Genmab and AbbVie, is an IgG1-bispecific antibody created using Genmab's DuoBody® technology. It is designed to bind simultaneously to CD3 on T cells and CD20 on B cells, inducing T-cell-mediated killing of CD20+ cells. Epcoritamab is approved under the brand name EPKINLY in the U.S. and Japan, and TEPKINLY in the EU, for certain lymphoma indications.
Mariana Cota Stirner, M.D., Ph.D., vice president, therapeutic area head for hematology, AbbVie, stated, "The results from these epcoritamab studies help provide confidence in our ongoing Phase 3 trials and highlight our commitment to advancing treatment standards for this challenging type of cancer. We remain dedicated to exploring epcoritamab both as a monotherapy and in combination with other therapies for earlier lines of treatment, as well as establishing it as a core therapy across B-cell malignancies."
