At the 66th Annual Meeting of the American Society of Hematology (ASH), AbbVie shared new data from two ongoing clinical trials evaluating epcoritamab, a CD3xCD20 bispecific T-cell-engaging antibody. Administered subcutaneously, epcoritamab demonstrated encouraging outcomes in adult patients with diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin lymphoma (NHL).
High Efficacy in First-Line Treatment
In the Phase 1b/2 EPCORE NHL-2 multi-arm trial, epcoritamab was combined with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in untreated high-risk DLBCL patients. Among 46 evaluable patients with International Prognostic Index (IPI) scores of 3 to 5—a group with poor long-term outcomes—100% achieved an overall response rate (ORR), and 87% attained a complete response (CR). Remarkably, 83% of those achieving a CR remained in remission after two years.
Minimal residual disease (MRD) analysis from blood samples revealed that 91% of patients achieved MRD negativity, signifying no detectable disease as assessed by circulating tumor DNA (ctDNA).
The most common treatment-emergent adverse events (TEAEs) included neutropenia (70%), anemia (69%), cytokine release syndrome (CRS, 60%), fatigue (49%), and nausea (47%). CRS events, mostly mild to moderate, occurred predominantly after the first full dose and resolved in all cases. Two patients experienced immune effector cell-associated neurotoxicity syndrome (ICANS), both of which resolved without treatment discontinuation.
Promising Durability in Third-Line Treatment
Three-year follow-up results from the Phase 2 EPCORE NHL-1 trial evaluated epcoritamab monotherapy in 157 adult patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) who had undergone at least two prior lines of therapy. The study showed durable responses in this challenging-to-treat population, with a 41% CR rate. Among patients achieving CR, 52% maintained their response at three years, with a median CR duration of 36.1 months.
MRD analysis indicated that 45.4% of patients achieved MRD negativity, reflecting effective disease control.
The most frequent TEAEs were CRS (51%), fatigue (25%), and fever (25%). Although 20 patients experienced fatal TEAEs, 10 of these were attributed to COVID-19, reflecting ongoing challenges in managing immunocompromised populations. Over two years, 73% of patients avoided severe infections, and cytopenia rates declined significantly after the first eight weeks of treatment.
Addressing Challenges in DLBCL
DLBCL is a fast-growing cancer affecting B-cell lymphocytes, often arising in lymph nodes or external organs. It accounts for 25-30% of all NHL cases globally, with approximately 25,000 new cases diagnosed annually in the U.S. The disease disproportionately affects older adults and men. Despite advancements in therapies, managing relapsed or refractory DLBCL remains a significant challenge, underscoring the need for novel approaches.
“More first-line treatments for DLBCL are needed, especially for patients with aggressive disease markers that may reduce the efficacy of standard therapies,” noted Dr. Lorenzo Falchi, a lymphoma specialist at Memorial Sloan Kettering Cancer Center. “The durable responses observed in this study suggest significant potential for epcoritamab-based combinations.”
Advancing Treatment Standards
The results presented at ASH bolster confidence in AbbVie’s ongoing Phase 3 trials, aiming to establish epcoritamab as a core therapy across B-cell malignancies. AbbVie is committed to exploring its use both as a standalone treatment and in combination with other therapies, potentially improving outcomes for patients with challenging lymphoma subtypes.
“The findings from these epcoritamab studies highlight our dedication to redefining treatment paradigms for aggressive cancers like DLBCL,” said Dr. Mariana Cota Stirner, Vice President and Therapeutic Area Head for Hematology at AbbVie.
Regulatory Landscape
Epcoritamab is approved for specific lymphoma indications in the U.S. (under the brand name EPKINLY), Japan, and the EU (TEPKINLY). However, its combination with R-CHOP in first-line DLBCL remains investigational and is not yet approved in any territory. Ongoing trials will further evaluate its safety and efficacy in this context.
A Path Toward Better Outcomes
Epcoritamab’s demonstrated durability and safety profile in both first-line and later-line DLBCL treatments signal meaningful progress for patients facing aggressive disease. As research continues, the hope is to provide broader access to innovative, life-extending therapies for those affected by this challenging cancer.
