Epcoritamab Combo Trial Results

Among 111 patients with a median follow-up of over two years, overall response rate (ORR) was 96%, and complete response (CR) rate was 87%. The data (Abstract #342) were shared at ASH 2024.

"These data highlight the potential benefits of epcoritamab in treating patients with relapsed or refractory follicular lymphoma. Moreover, they show that epcoritamab in combination with the commonly used therapy of lenalidomide with rituximab (R²) could offer a potentially strong and durable treatment option," said Dr. Mariana Cota Stirner,  vice president, therapeutic area head for hematology, AbbVie. "These data are very encouraging as we continue to further evaluate the potential of epcoritamab in combination with R² in an ongoing pivotal Phase III trial and further establish epcoritamab as a core therapy for the treatment of B-cell malignancies."

FL is typically an indolent (or slow-growing) form of non-Hodgkin's lymphoma (NHL) that arises from B-lymphocytes and is the second most common form of NHL accounting for 20-30% of all cases. About 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 and, with each relapse the remission and time to next treatment is shorter. Over time, transformation to diffuse large B-cell lymphoma (DLBCL), an aggressive form of NHL associated with poor survival outcomes, can occur in more than 25% of FL patients.

Overview of Phase Ib/II EPCORE NHL-2 Data Results: This study's primary endpoint was ORR per Lugano criteria, and adult patients with R/R FL received subcutaneous epcoritamab + R² for up to 12 cycles, followed by 12 additional cycles of epcoritamab monotherapy (28 days each cycle). Among 111 patients with a median follow-up of over two years, the ORR was 96%, and the CR rate was 87%. At 18 months an estimated 89% of complete responders to the combination therapy remained in CR (duration of CR; DoCR), 41 patients completed treatment per protocol. Minimal residual disease (MRD) analysis from blood samples showed that 88% of patients were MRD negative, indicating no detectable disease at 10^-6 threshold. 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.

About the EPCORE NHL-2 Trial: EPCORE NHL-2 is a Phase Ib/II open-label interventional trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics/biomarkers, immunogenicity, and preliminary efficacy of epcoritamab as a monotherapy and in combination with other standard of care agents in patients with B-cell non-Hodgkin's lymphoma (B-NHL). The trial consists of two parts: Part 1 (Dose Escalation) and Part 2 (Dose Expansion). The primary objective of Part 1 is safety, and it includes Arm 1-5 and Arm 10. Part 2 includes all 10 arms (Arm 1-10) and the primary goal of all arms, except Arm 7, is preliminary efficacy. Arm 2 of the trial is epcoritamab + rituximab and lenalidomide (R²) in participants with relapsed/refractory (R/R) follicular lymphoma (FL). More information on this trial can be found at https://www.clinicaltrials.gov/ (NCT: 04663347). The primary endpoint was overall response rate (ORR) based on best overall response per Lugano criteria. MRD negativity was assessed as a secondary endpoint.