Epcoritamab-bysp Yields Long-Term Disease Remission in Patients with Relapsed, Refractory Large B-Cell Lymphoma

Epcoritamab-bysp (Epcor, Epkinly; Genmab, AbbVie) yields significant long-term disease remission in patients with relapsed, refractory large B-cell lymphoma (R/R LBCL), according to 3-year follow-up data from the EPCORE NHL-1 study (NCT03625037). The findings are to be presented at the 2025 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois.¹

Lymphoma cell | Image Credit: © Dr_Microbe - stock.adobe.com

Epcor is a bispecific T-cell engager (BiTE) that selectively binds to CD3 on healthy T-cells and CD20 on cancerous B cells to induce apoptosis. In 2023, it received accelerated approval from the FDA for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after 2 or more lines of systemic therapy, which was based on positive data from the EPCORE NHL-1.^2,3

EPCORE NHL-1 is a phase 1/2, open-label trial designed to determine the maximum tolerated dose and establish the safety of epcor in patients with R/R LBCL who previously received 2 or more prior lines of therapy. Epcor was administered subcutaneously in 28-day cycles (C; 0.16- and 0.8-mg step-up doses in C1; 48 mg full dose thereafter; once weekly [QW], C1–3; Q2W, C4–9; Q4W, C≥10) until progressive disease (PD) or unacceptable toxicity. The primary end point was overall response rate (ORR).^1,4

In the 3-year follow-up, epcor led to lasting complete responses (CR), with a median CR duration of 36 months, median progression-free survival (PFS) of 37 months, and median overall survival (OS) not yet reached in patients who achieved a complete response. This report shares long-term results from a post-hoc analysis of patients who were still in complete response 2 years after starting treatment—referred to here as patients in CR at 2 years.⁴

At the median follow-up of 37 months (range: 32–46 months), about 41% of patients achieved a CR, of which 49% maintained their responses at 2 years, and all but one achieved a response by the second assessment at week 12. Further, approximately 96% of patients remained in CR at 3 years, and the longest ongoing CR at the time of analysis exceeded 43 months.⁴

Patients in CR at 2 years received a median of 35 months of treatment (range: 8–43 months), and 81% (26 of 32) were still on treatment at the 2-year mark. Among these, 19% experienced at least 1 serious infection after 2 years, most commonly pneumonia, and 2 patients died because of COVID-19 pneumonia and bacterial pneumonia. At the data cutoff, 59% were still receiving treatment. One patient discontinued due to disease progression, whereas 12 discontinued for other reasons, most commonly adverse events. Among those who discontinued for reasons other than disease progression, CR was maintained for a median of 14 months (range: 2–28 months) after stopping treatment.⁴

This post-hoc analysis highlights the promising efficacy and safety of epcoritamab in patients with relapsed or refractory large B-cell lymphoma (R/R LBCL), supporting its potential as a treatment option in later-line settings.

REFERENCES

1. First-in-human (FIH) trial in patients with relapsed, progressive or refractory b-cell lymphoma (EPCORE™ NHL-1). Updated May 8, 2025. Accessed May 28, 2025. https://clinicaltrials.gov/study/NCT03625037

2. Epcoritamab-bysp. National Cancer Institute. June 28, 2024. Accessed May 28, 2025. https://www.cancer.gov/about-cancer/treatment/drugs/epcoritamab-bysp

3. 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 May 28, 2025. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-epcoritamab-bysp-relapsed-or-refractory-diffuse-large-b-cell

4. Karimi Y, Vose J, Clausen M, et al. Novel analysis of 3-y results from the pivotal EPCORE NHL-1 study: Outcomes in patients (pts) with relapsed/refractory large B-cell lymphoma (R/R LBCL) and complete response (CR) at 2 y with epcoritamab (epcor) monotherapy. 2025 ASCO Annual Meeting. May 30, 2025, to June 3, 2025. Chicago, IL. Abstract 7043