Epcoritamab Plus Rituximab/Lenalidomide Generates Promising Responses in High-Risk R/R Follicular Lymphoma

Phase I/II EPCORE NHL-2 trial

Epcoritamab is a novel bispecific antibody that targets CD3 and CD20 and induces T-cell–mediated cytotoxic activity against CD20-positive malignant B cells. During the ASCO Annual Meeting 2023, a comprehensive analysis was presented, pooling data from cohorts 2a and 2b of the ongoing Phase I/II EPCORE NHL-2 trial (NCT04663347). This trial, known as EPCORE NHL-2, aims to investigate the efficacy of the T-cell engager bispecific antibody called epcoritamab in various combinations for patients diagnosed with B-cell non-Hodgkin lymphoma. Cohorts 2a and 2b specifically focus on patients with relapsed or refractory follicular lymphoma who are receiving subcutaneous administration of epcoritamab in combination with R2 therapy.

Arm 2a of the trial enrolled individuals diagnosed with relapsed or refractory CD20-positive follicular lymphoma. They underwent a 12-cycle treatment regimen comprising subcutaneous administration of epcoritamab at a dose of 48 mg in combination with R2 therapy. Epcoritamab was administered weekly during the first three cycles, followed by every other week for cycles 4-9, and subsequently every four weeks from cycle 10 onwards. Participants in arm 2b, another group with relapsed or refractory CD20-positive follicular lymphoma, received the same treatment but with a different dosing schedule. Epcoritamab was administered once weekly for the initial two cycles and then every four weeks for the following cycles. The treatment duration for both arms lasted up to two years.

In the group of 104 patients who were evaluated for efficacy and received a combination of epcoritamab at a dose of 48 mg along with R2 therapy, the overall response rate (ORR) was found to be 98%. The ORR specifically to the immediate prior therapy was 85% at the data cutoff on January 31, 2023, with a median follow-up of 11.4 months. For the current therapy with epcoritamab, the complete metabolic response (CMR) was observed in 87% of patients, whereas it was 58% for the immediate prior therapy. Additionally, partial metabolic response (PMR) was observed in 12% and 27% of patients, stable disease in 1% and 5%, and progressive disease in 1% and 7%, respectively, for each treatment arm.

Across various subgroups, high overall response rate (ORR) and complete metabolic response (CMR) rates were consistently observed, with an ORR of 95% or greater in all groups. Specifically, patients who experienced disease progression within 24 months (POD24) exhibited a 75% CMR and 22.5% partial metabolic response (PMR), with an overall ORR of 98%.

In terms of safety, the analysis included 111 patients from cohorts 2a and 2b of the EPCORE NHL-2 trial, and the findings were consistent with previous reports. Treatment-emergent adverse events (TEAEs) of Grade 3 or higher were observed in 76% of patients, with 41% being related to subcutaneous epcoritamab (SC) administration. Immune effector cell-associated neurotoxicity syndrome occurred in 2% of patients, with a median resolution time of 5.5 days.

Delays in treatment due to TEAEs were necessary for 61% of patients, with 29% of those delays being related to SC epcoritamab. Thirteen percent of patients discontinued SC epcoritamab, with 5% discontinuing specifically due to SC epcoritamab.

Further exploration of cytokine release syndrome (CRS) events indicated that CRS occurrence was predictable. The majority of events were of low grade, and all events were resolved. The median time to resolution was 3 days, and 13% of patients received treatment with tocilizumab. No patients discontinued SC epcoritamab due to CRS.

KOL insights

“Based on these encouraging results, epcoritamab-based combinations are being studied in an ongoing, randomized phase 3 trial, the EPCORE FL-1 trial (NCT05409066), as well as in a non-randomized POD24 cohort in the EPCORE NHL-2 trial.” –Expert Opinion.

“The addition of epcoritamab to R2 leads to deep and so far, quite durable remissions in R/R FL, including POD24 patients and other high-risk populations. High overall and complete response rates were observed across all different patient subgroups.” –Expert Opinion.


Exciting developments have taken place in the field of lymphoma treatment with the US FDA granting accelerated approval to epcoritamab, marking a significant milestone in the fight against relapsed/refractory diffuse large B-cell lymphoma. This approval specifically caters to adults who have undergone at least two lines of systemic therapy. The impressive findings presented at ASCO 2023 have sparked new research opportunities. Epcoritamab-based combinations are now the focus of the Phase III EPCORE FL-1 trial (NCT05409066), where their potential is being rigorously evaluated in a randomized setting. Furthermore, the non-randomized POD24 cohort within the EPCORE NHL-2 trial is also being investigated, adding another dimension to the search for improved treatments