Epcoritamab, a CD3xCD20 bispecific T-cell-engaging antibody, in combination with lenalidomide and rituximab (R2), has demonstrated promising results in patients with relapsed or refractory (R/R) follicular lymphoma (FL). The Phase 1b/2 EPCORE® NHL-2 trial, evaluating this fixed-duration investigational therapy, reported a 96% overall response rate (ORR) and an 87% complete response (CR) rate among 111 patients with a median follow-up of over two years. These findings, presented at the 66th Annual Meeting and Exposition of the American Society of Hematology (ASH), highlight the potential of epcoritamab as a durable treatment option for B-cell malignancies.
High Response Rates and Durability
The EPCORE® NHL-2 trial's primary endpoint was ORR per Lugano criteria. Adult patients with R/R FL received subcutaneous epcoritamab + R2 for up to 12 cycles, followed by 12 additional cycles of epcoritamab monotherapy. The study revealed that an estimated 89% of complete responders to the combination therapy remained in CR at 18 months (duration of CR; DoCR). Minimal residual disease (MRD) analysis from blood samples showed that 88% of patients were MRD negative, indicating no detectable disease at a threshold of 10-6.
Mariana Cota Stirner, M.D., Ph.D., vice president, therapeutic area head for hematology, AbbVie, noted, "These data highlight the potential benefits of epcoritamab in treating patients with relapsed or refractory follicular lymphoma... [it] could offer a potentially strong and durable treatment option."
Follicular Lymphoma Context
FL, an indolent form of non-Hodgkin's lymphoma (NHL), arises from B-lymphocytes and accounts for 20-30% of all NHL cases. Approximately 15,000 people develop FL each year in the U.S., and it is considered incurable with current standard of care therapies. Patients often relapse, with each relapse resulting in shorter remission and time to next treatment. Over time, FL can transform into diffuse large B-cell lymphoma (DLBCL), an aggressive form of NHL associated with poor survival outcomes, in more than 25% of patients.
FDA Breakthrough Therapy Designation
The U.S. Food and Drug Administration (FDA) recently granted breakthrough therapy designation (BTD) for epcoritamab plus R2 for the treatment of adult patients with R/R FL who have received at least one prior line of therapy. This designation underscores the potential of epcoritamab, which is being further studied in the ongoing, randomized, Phase 3 EPCORE FL-1 trial (NCT05409066).
Safety Profile
COVID-19 was reported in 57% of patients and led to epcoritamab discontinuation in 13% of patients. Five cases of COVID-19 led to fatal treatment-emergent adverse events (TEAEs; COVID-19, n=3; COVID-19 pneumonia, n=2). The other most common TEAEs were neutropenia (62%) and cytokine release syndrome (CRS; 51%). CRS events with the 2-step step-up dose regimen were mostly low grade (38% Grade 1, 12% Grade 2, 2% Grade 3) and primarily occurred following the first full dose. All CRS cases resolved. One case of immune effector cell-associated neurotoxicity syndrome (ICANS) was reported (Grade 1). The CRS and ICANS cases did not lead to treatment discontinuation.
Lorenzo Falchi, M.D., Lymphoma Specialist, Department of Medicine, Memorial Sloan Kettering Cancer Center, stated, "The durable responses seen in the EPCORE NHL-2 trial support the ongoing investigation of epcoritamab in combination with the standard regimen of rituximab plus lenalidomide."
Ongoing Research
Genmab and AbbVie continue to evaluate the use of epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies. This includes five ongoing Phase 3, open-label, randomized trials, further solidifying epcoritamab's potential as a core therapy for B-cell malignancies.
