Initial Data Analysis Shows 95% Response Rate for Epcoritamab Combo in Untreated Follicular Lymphoma

Copenhagen, Denmark; June 2, 2024 – Genmab (Nasdaq: GMAB) has released new data from two ongoing clinical trials evaluating the efficacy and safety of epcoritamab, a T-cell engaging bispecific antibody, in patients with various forms of follicular lymphoma (FL).

The EPCORE™ NHL-2 study (NCT04663347) demonstrates a remarkable overall response rate (ORR) of 95% and a complete response rate (CRR) of 85% when epcoritamab is combined with rituximab-lenalidomide (R2) in patients with previously untreated FL. These results were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. However, it is important to note that the safety and efficacy of this treatment approach have not yet been officially established.

The EPCORE™ NHL-1 study (NCT03625037) focused on patients with relapsed/refractory (R/R) FL and highlighted significant reductions in cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) due to optimized mitigation strategies. CRS was reported in 49% of patients in the optimized cohort, a decrease from 66% in the pivotal group. Moreover, there were no occurrences of Grade 3 or higher CRS events or ICANS, which are serious adverse reactions requiring careful monitoring.

"Follicular lymphoma is considered incurable, and patients across all stages need innovative treatment options," stated Judith Klimovsky, Executive Vice President & Chief Development Officer at Genmab. The data from ASCO indicate that epcoritamab may offer promising outcomes for FL patients, whether newly diagnosed or post-relapse. Klimovsky emphasized the importance of reducing CRS and ICANS incidences through optimized dosing safety for patients with relapsed/refractory diseases.

Detailed Findings from EPCORE™ NHL-2

The EPCORE NHL-2 study included results from two arms. Arm 6 assessed epcoritamab in combination with R2 in untreated FL patients, showing durable responses with 89% of patients remaining progression-free and 93% maintaining complete response (CR) at 18 months. Common treatment-emergent adverse events (TEAEs) included COVID-19 (63%), CRS (56%), and neutropenia (56%). All CRS events were low grade and resolved without leading to treatment discontinuation.

Arm 7 evaluated epcoritamab administered every eight weeks for patients in CR or partial response (PR) following standard-of-care treatment. The results revealed that 100% of patients who entered with a PR converted to a CR, and 90% remained alive at 21 months. TEAEs included COVID-19 (70%) and CRS (55%), with only one Grade 1 CRS event occurring during maintenance dosing.

Insights from EPCORE™ NHL-1

The C1 optimization cohort in EPCORE™ NHL-1 involved patients with R/R FL who received epcoritamab in three step-up doses, with additional prophylactic measures to mitigate CRS. The study showed a 49% CRS rate, primarily occurring during the first treatment cycle, with all events resolving. Importantly, there were no ICANS events, and the ORR was 91% with a CR rate of 68%, suggesting that the mitigation measures did not compromise the treatment's efficacy.

Regulatory and Future Directions

On February 26, 2024, the FDA granted Priority Review for the supplemental Biologics License Application (sBLA) for epcoritamab for treating adult patients with R/R FL after two or more lines of systemic therapy. Currently, the use of epcoritamab in FL is not approved in the U.S., the EU, or any other territory.

Genmab continues to evaluate epcoritamab in various clinical settings, including four ongoing Phase 3 trials. These trials are investigating the antibody as a monotherapy and in combination with other treatments across different B-cell malignancies.

About Epcoritamab

Epcoritamab is a bispecific antibody created using Genmab's DuoBody® technology, designed to engage and direct T cells to target and kill malignant B cells. The antibody has received regulatory approval for certain lymphoma indications in various regions and is being co-developed with AbbVie. The two companies share commercial responsibilities in the U.S. and Japan, with AbbVie handling further global commercialization.

Genmab aims to continue the development of epcoritamab as a core therapy for B-cell malignancies, striving to provide new treatment options for patients with limited therapeutic choices.

How to obtain the latest research advancements in the field of biopharmaceuticals?

In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!