Epcoritamab Receives UK Approval for R/R DLBCL After 2 Prior Lines of Therapy

The United Kingdom’s Medicines and Healthcare Products Regulatory Agency has granted conditional marketing authorization to epcoritamab-bysp (Tepkinly) monotherapy for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after 2 or more systemic therapy.^1,2

The decision was supported by data from the phase 1/2 EPCORE NHL-1 trial (NCT03625037), which showed that patients with DLBCL treated with epcoritamab (n = 139) experienced an overall response rate (ORR) of 62% and a complete response (CR) rate of 39%.²

“Despite recent therapeutic advances, treatment options for patients with R/R DLBCL after 2 previous therapies are limited. For such patients living with this type of aggressive blood cancer, many experience disease progression and have poor prognosis”, Dr Chris Fox, a professor of hematology in the School of Medicine at the University of Nottingham and honorary consultant hematologist at Nottingham University Hospitals NHS Trust in the United Kingdom, stated in a news release.¹ “As a novel bispecific antibody, given as a subcutaneous injection, epcoritamab offers a new treatment option for this difficult-to-treat patient group.”

In September 2023, the European Commission granted conditional marketing authorization to epcoritamab for use as a single agent in adult patients with relapsed or refractory DLBCL following 2 or more lines of systemic treatment.³ Furthermore, the FDA approved the bispecific antibody for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified (NOS), including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma (HGBCL), after 2 or more lines of systemic therapies, in May 2023.⁴

Those regulatory decisions were also based on findings from EPCORE NHL-1. The single-arm, open-label, multicenter trial enrolled patients at least 18 years of age with CD20-positive mature B-cell neoplasms, including DLBCL and other aggressive non-Hodgkin lymphomas such as primary mediastinal large B-cell lymphoma, HGBCL, and follicular lymphoma grade 3B.⁵

All patients needed to have relapsed, progressive, and/or refractory disease following treatment with a CD20-targeted monoclonal antibody–containing regimen and prior failure of or ineligibility for autologous stem cell transplant. An ECOG performance status of 0 to 2 was also required. Patients were excluded if they had primary central nervous system (CNS) lymphoma or CNS involvement by lymphoma.

During the dose-expansion portion of the study, patients received step-up dosing during cycle 1 which consisted of a 0.16-mg priming dose on day 1 followed by a 0.8-mg intermediate dose on day 8. On day 15 and beyond, epcoritamab was given at 48 mg until disease progression or unacceptable toxicity. The agent was given once per week in cycles 1 to 3, then once every 2 weeks in cycles 4 to 9, and once every 4 weeks thereafter.

ORR as assessed by an independent review committee per Lugano criteria served as the trial’s primary end point. Secondary end points included duration of response (DOR), CR rate, duration of CR, progression-free survival (PFS), time to response, and overall survival.

Additional data from the DLBCL cohort showed that the median DOR was 15.6 months. The median PFS was 19.4 months.2

Regarding safety, the most common any-grade adverse effects (AEs) reported in at least 20% of patients included cytokine release syndrome (CRS; 50.9%), fatigue (30.5%), neutropenia (30.5%), injection-site reactions (29.9%), pyrexia (23.4%), abdominal pain (23.4%), nausea (21.6%), and diarrhea (21.0%). Grade 3 or 4 AEs that occurred in at least 2% of patients consisted of neutropenia (23.4%), anemia (10.2%), thrombocytopenia (7.2%), pneumonia (6.0%), fatigue (3.0%), CRS (3.0%), febrile neutropenia (2.4%), edema (2.4%) and hypophosphatasemia (2.4%).

Furthermore, serious AEs observed in at least 2% of patients included CRS (31.1%), pneumonia (7.2%), upper respiratory tract infections (2.4%), febrile neutropenia (2.4%), immune effector cell–associated neurotoxicity syndrome (ICANS; 2.4%) and pyrexia (2.4%).

Fatal AEs were reported in 2.4% of patients, including ICANS (n = 1; 0.6%) and pneumonia (n = 3; 1.8%).

References

1. MHRA authorises bispecific antibody therapy Tepkinly as a treatment for diffuse large B-cell lymphoma in adults. News release. Medicines and Healthcare Products Regulatory Agency. October 20, 2023. Accessed October 23, 2023. https://www.gov.uk/government/news/mhra-authorises-monoclonal-antibody-therapy-tepkinly-as-a-treatment-for-diffuse-large-b-cell-lymphoma-in-adults
2. MHRA grants conditional marketing authorisation for Tepkinly (epcoritamab) as a bispecific treatment for adults with relapsed or refractory DLBCL after two or more lines of systemic therapy. News release. AbbVie. October 23, 2023. Accessed October 23, 2023. https://news.cision.com/abbvie/r/mhra-grants-conditional-marketing-authorisation-for-tepkinly-epcoritamab--as-a-bispecific-treatment-,c3858118
3. Genmab announces European Commission approval of Tepkinly (epcoritamab) for adults with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). News release. Genmab A/S. September 25, 2023. Accessed October 23, 2023. https://ir.genmab.com/news-releases/news-release-details/genmab-announces-european-commission-approval-tepkinlyr
4. FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory diffuse large B-cell lymphoma and high-grade B-cell lymphoma. FDA. May 19, 2023. Accessed October 23, 2023. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-epcoritamab-bysp-relapsed-or-refractory-diffuse-large-b-cell
5. Thieblemont C, Phillips T, Ghesquieres H, et al. Epcoritamab, a novel, subcutaneous CD3xCD20 bispecific T-cell-engaging antibody, in relapsed or refractory large B-cell lymphoma: dose expansion in a phase I/II trial. J Clin Oncol. 2023;41(12):2238-2247. doi:10.1200/JCO.22.01725