Genmab’s epcoritamab therapy delivers promising results for relapsed follicular lymphoma

Relapsed or refractory follicular lymphoma (FL) remains a persistent challenge for patients, particularly those with high-risk features. Genmab A/S, alongside its development partner AbbVie, announced exceptional results from the Phase 1b/2 EPCORE NHL-2 trial at the 66th Annual Meeting of the American Society of Hematology (ASH). The trial showcased the efficacy of epcoritamab, a T-cell-engaging bispecific antibody, in combination with rituximab and lenalidomide (R2). With an overall response rate (ORR) of 96% and a complete response (CR) rate of 87% among 111 patients after a median follow-up of two years, the investigational therapy is poised to reshape treatment strategies.

Epcoritamab, based on Genmab’s proprietary DuoBody technology, works by simultaneously binding to CD3 on T cells and CD20 on B cells, promoting targeted immune responses against cancer cells. The trial also reported an estimated progression-free survival (PFS) rate of 80% at 21 months and a two-year overall survival (OS) rate of 90%, further underscoring its clinical potential.

COVID-19’s impact and durable outcomes

The EPCORE NHL-2 trial, conducted amid the global COVID-19 pandemic, faced significant challenges. More than half of the participants contracted COVID-19 during the study, leading to therapy discontinuation in 13% of cases. Unfortunately, five patients succumbed to COVID-19-related complications. Despite these setbacks, the trial demonstrated remarkable durability, with 89% of complete responders maintaining remission at 18 months.

Dr. Lorenzo Falchi from Memorial Sloan Kettering Cancer Center noted that the long-term efficacy seen in this study supports epcoritamab’s potential as a much-needed option for relapsed or refractory FL patients. He highlighted that durable response rates represent critical progress in an area with limited therapeutic alternatives.

Adverse events and safety profile

While promising, the treatment’s safety profile requires attention. Common treatment-emergent adverse events (TEAEs) included neutropenia (62%) and cytokine release syndrome (CRS; 51%), which was predominantly low-grade and resolved post-treatment. Additionally, one case of immune effector cell-associated neurotoxicity syndrome (ICANS) was reported but did not lead to therapy discontinuation.

Epcoritamab is currently approved under the brand name EPKINLY for certain lymphoma indications in select regions, including the U.S. and Japan. Regulatory efforts continue to expand its approved applications, with further studies planned to confirm its safety and efficacy in additional settings.

Genmab’s vision for epcoritamab

Building on these results, Genmab is advancing the EPCORE FL-1 Phase 3 trial to further evaluate epcoritamab in relapsed FL. The therapy has already received breakthrough therapy designation (BTD) from the U.S. Food and Drug Administration, a status expected to expedite its development and review process.

Dr. Judith Klimovsky, Chief Development Officer at Genmab, stated that the findings from the EPCORE NHL-2 trial reaffirm epcoritamab’s potential as a cornerstone therapy for B-cell malignancies. She emphasised the company’s commitment to broadening the scope of epcoritamab’s applications, both as a monotherapy and in combination with established treatment regimens.

Looking ahead: expanding therapeutic boundaries

Epcoritamab’s future extends beyond follicular lymphoma. Genmab and AbbVie are investigating its efficacy across a range of hematologic cancers, including diffuse large B-cell lymphoma (DLBCL). Ongoing trials are exploring combinations with first-line regimens, such as R-CHOP, and evaluating the therapy’s standalone effectiveness compared to chemotherapy.

As Genmab and AbbVie progress toward additional regulatory approvals, epcoritamab’s robust clinical data and promising safety profile suggest a transformative role in oncology. If successfully developed across multiple indications, the therapy could set a new benchmark for treating relapsed lymphomas and other B-cell malignancies.