DDW Editor Reece Armstrong speaks to Tahi Ahmadi, MD, PhD, Executive Vice President & Chief Medical Officer, Head of Experimental Medicines, Genmab & Jacqueline Nielsen, PhD, Therapeutic Head, Hematology, AbbVie, about the recommendation and the development of epcoritamab.

Earlier this year, the European Medicines Agenecy’s (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended conditional marketing authorisation for epcoritamab (TEPKINLY), based on data for the Phase I/II EPCORE NHL-1 study. Epcoritamab is being co-developed by AbbVie and Genmab as part of the companies’ oncology collaboration for patients with relapsed/refractory (R/R) follicular lymphoma (FL) and R/R diffuse large B-cell lymphoma (DLBCL), after two or more lines of prior therapy. 

If approved, epcoritamab will be the first and only bispecific antibody approved as a monotherapy in the European Union for patients with R/R FL and R/R DLBCL. 

RA: How encouraging is it that TEPKINLY has been recommended CMA for R/R + FL a year after being approved for DLBCL? 

JN: The European Commission decision on this indication for epcoritamab is anticipated later this year. As background, on June 28, 2024, the EMA’s CHMP adopted a positive opinion recommending the conditional marketing authorisation of epcoritamab (TEPKINLY) as a monotherapy for the treatment of adult patients with R/R FL after two or more prior therapies.

RA: How pleased were you with the data from the EPCORE study and  the positive decision by the EMA?

JN: We were pleased with the positive overall and complete response data from the Phase I/II EPCORE NHL-1 study in follicular lymphoma (FL), which supported the EU filing. The positive CHMP opinion recognises the unmet need for people whose disease is considered difficult-to-treat and that epcoritamab may represent a new therapeutic option. If approved, epcoritamab will become the first and only bispecific antibody approved as a monotherapy in the EU to treat both R/R FL and R/R diffuse large B-cell lymphoma (DLBCL), after two or more lines of prior therapy. 

RA: What’s the current unmet need for relapsed/refractory follicular lymphoma? 

JN: 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. In 2023, there were an estimated 13,000 cases of FL in Western Europe. FL is considered incurable with current standard of care therapies.

Patients with FL typically face disease recurrence and shorter durability of response with each subsequent line of therapy. This positive opinion recognises the unmet need for people whose disease is considered challenging to treat.

RA: What are the benefits of subcutaneous injection? 

JN: Epcoritamab’s subcutaneous administration may provide eligible patients with a safe, effective and comfortable treatment option that enables accelerated treatment initiation across practice settings, including outpatient, to address high clinical need. Subcutaneous administration also allows more gradual increases and lower peaks in plasma cytokine levels than IV administration. Additionally, as an off-the-shelf treatment option, epcoritamab can be made available to treat patients at the moment of relapse.

RA: Epcoritamab doesn’t require cell collection and engineering. Will this help improve the availability of the treatment? 

JN: If approved in FL, epcoritamab (TEPKINLY) may offer an alternative to therapies such as CAR-T, which tend to have strict eligibility criteria and pose logistical challenges for patients by having long wait times, which may cause challenges for patients who urgently need treatment.   

RA: Are you concerned about cytokine release syndrome with this therapy?

TA: Cytokine release syndrome (CRS) is an associated side effect from immune-engaging cancer treatments. The safety profile of epcoritamab in the pivotal cohort was similar to reports of epcoritamab monotherapy in the pivotal EPCORE NHL-1 DLBCL cohort. Importantly, the EPCORE NHL-1 data supporting this submission included an additional cohort of 86 patients, which evaluated a three-step-up dosing (SUD) schedule to reduce the incidence and severity of CRS. For the first full dose of this three-step regimen, mandatory hospitalisation was not required. In this cohort, the incidence of CRS was 49% (42 of 86 patients; 9% were grade 2). There were no grade 3 or higher CRS events. The data from this optimisation cohort of the EPCORE NHL-1 study were recently published in the Lancet Haematology¹.

RA: Why are additional lines of therapy so important for patients with these forms of cancer? 

TA: FL is considered incurable with current standard of care therapies, and patients with FL are likely to face disease recurrence and shorter durability of response with each subsequent line of therapy. This positive opinion recognises the unmet need in the European Union for individuals with relapsed or refractory follicular lymphoma, especially those who failed multiple therapies. 

If approved, epcoritamab will offer an accessible, off-the-shelf, T-cell engaging treatment option that enables accelerated treatment initiation across practice settings, including outpatient, to address high clinical need.

RA: Could you discuss epcoritamab’s mode of action?

TA: Epcoritamab is an investigational IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology and administered subcutaneously. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response toward targeted cell types.

Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T-cell-mediated killing of CD20+ cells. 

RA: Could you comment on the collaboration with Genmab? 

TA: AbbVie and Genmab are committed to developing epcoritamab as a core therapy for the treatment of multiple B-cell malignancies. Epcoritamab is being co-developed by AbbVie and Genmab as part of the companies’ broad oncology collaboration. AbbVie will continue to pursue regulatory submissions for epcoritamab across international markets. Both Genmab and AbbVie continue to evaluate the use of epcoritamab as a monotherapy and in combination across lines of therapy in a range of haematologic malignancies.

From DDW Volume 25 – Issue 4, Fall 2024 Read the digital issue

Reference:

1. https://www.sciencedirect.com/science/article/abs/pii/S2352302624001662?dgcid=author 

Biographies:

Jacqueline Nielsen, PhD, is the Therapeutic Area Head of Hematologic Oncology Affairs at AbbVie. She has extensive experience in early drug development, laboratory assays and methodology, basic science, and translational research.

Dr Ahmadi joined Genmab in 2017 and became the Executive Vice President and Chief Medical Officer, Head of Experimental Medicines effective March 1, 2021. He holds an MD from the University of Cologne (Germany) and a PhD from the University of Freiburg (Germany) and has expertise in translational research, strategic product development, global regulatory submissions and clinical development. Prior to joining Genmab, Dr Ahmadi was head of experimental medicine and early development oncology at Janssen and a member of the Senior Leadership Team for Oncology.