Epcoritamab Elicited Sustained PFS and OS at 3 Years in R/R LBCL

Epcoritamab monotherapy led to long-term disease-free remissions in patients with relapsed/refractory large B-cell lymphoma who achieved complete response at 2 years.

An analysis of the phase 2 EPCORE NHL-1 trial (NCT03625037) indicated that patients with relapsed/refractory large B-cell lymphoma (LBCL) who maintained a complete response (CR) 2 years after initiating epcoritamab-bysp (Epkinly) monotherapy experienced durable responses and prolonged survival, according to data shared at the 2025 ASCO Annual Meeting.1

Long-term findings showed that all but 1 of the 32 patients who were in CR at 2 years achieved a partial response (PR) or CR by the second assessment at 12 weeks, with 11 PRs converting to CRs after the second response assessment. Four patients had stable disease at their first disease assessment, all of whom went on to achieve CR.

Additional data showed that the median duration of CR (DOCR) was not reached (NR), and approximately 96% of patients remained in CR at 3 years, with the longest ongoing CR greater than 43 months. The median progression-free survival (PFS) and overall survival (OS) were both NR, with an estimated 96% and 97% of patients reported as progression free and alive, respectively, at 3 years.

“These findings underscore the benefits of treat-to-progression epcoritamab in the third-line and [beyond] setting, indicating that some patients obtain long-term remission,” lead study author Yasmin H. Karimi, MD, a clinical assistant professor of internal medicine in the Division of Hematology/Oncology at the University of Michigan in Ann Arbor, said in a poster presentation during the meeting.

Epcoritamab is a CD3xCD20-directed T-cell–engaging bispecific antibody that is indicated for patients with relapsed/refractory diffuse LBCL (DLBCL) not otherwise specified (NOS), including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma (HGBCL) after at least 2 lines of prior therapy.2 The FDA approved the agent for these indications in May 2023, and the regulatory decision was based on findings from the EPCORE NHL-1 study.

Long-term data from EPCORE NHL-1 showed that at 3 years, the median DOCR was 36.1 months (95% CI, 20.2-NR), the median PFS among complete responders was 37.3 months (95% CI, 26.0-NR), and the median OS among complete responders was NR.3

At the 2025 ASCO Annual Meeting, investigators reported results from a novel, post hoc analysis evaluating long-term outcomes in patients with relapsed/refractory LBCL who remained in CR 2 years after receiving single-agent epcoritamab in EPCORE NHL-1.1

To be eligible for enrollment, patients had to have relapsed/refractory CD20-positive mature B-cell neoplasm that was DLBCL (de novo or transformed), double- or triple-hit DLBCL, primary mediastinal B-cell lymphoma, HGBCL NOS, or grade 3B follicular lymphoma. Other enrollment requirements included an ECOG performance status of 0 to 2; 2 or more prior lines of systemic antineoplastic therapy, including at least 1 regimen with an anti-CD20 monoclonal antibody; and fluorodeoxyglucose PET–avid and measurable disease via CT/MRI. Prior CAR T-cell therapy was permitted.

As part of the phase 2 study design, epcoritamab was given subcutaneously at 48 mg until progressive (PD) disease or unacceptable toxicity in a dose-expansion cohort of 157 patients with LBCL.

Patients included in the post hoc analysis were in CR at 2 years following the start of treatment; end points assessed in the analysis included objective response rate via Lugano criteria, DOCR, PFS, OS, minimal residual disease (MRD) negativity rate, and safety composed of overall safety and safety after 2 years.

In the overall study population, 41% (n = 65) of 157 patients achieved a CR, with 32 of those patients remaining in CR 2 years after starting epcoritamab. Karimi noted that those in CR at 2 years had lower tumor burden at baseline; notably, bulky disease greater than 7 cm was seen in 19% of patients in CR at 2 years compared with 31% of patients in the overall population. Patients in CR at 2 years also had lower lactate dehydrogenase levels (294 U/L vs 338 U/L), and lower baseline ferritin levels (383 µg/L vs 406 µg/L) vs patients in the overall population. Rates of CAR T-cell therapy exposure were similar between the 2 populations, at 38% vs 39%, respectively.

The median follow-up for the post hoc analysis was 37 months (range, 32-46), and the median treatment duration was 35 months (range, 8-43). At this time point, 41% of patients had discontinued epcoritamab; discontinuations were mostly due to adverse effects (AEs; 19%), followed by other reasons (13%), PD (3%), no longer receiving a clinical benefit (3%), and patient withdrawal (3%). For the 12 patients who discontinued epcoritamab for reasons beyond PD, the median follow-up after discontinuation was 14 months (range, 2-28), during which none of the 12 patients relapsed.

Eighty-one percent of the 32 patients were on treatment at 2 years, with 59% of patients on treatment at the data cutoff.

Investigators also conducted an MRD analysis. Among patients who were MRD evaluable and had a CR 2 years after starting epcoritamab, 95% who were evaluable at day 1 of cycle 13 were MRD negative.

Regarding safety, 81% of patients had at least 1 treatment-emergent AE (TEAE) that led to a dose delay of epcoritamab. The most common TEAEs at any time during treatment were COVID-19 (66%), cytokine release syndrome (53%), and diarrhea (44%); after 2 years, the most common TEAEs that occurred were COVID-19 (34%), diarrhea (16%), upper respiratory tract infection (16%), decreased neutrophil count (13%), and pneumonia (13%). Nineteen percent of patients who were still on treatment at 2 years had at least 1 serious infection after that time point, most of which were cases of pneumonia (n = 4). Two patients died due to TEAEs (COVID-19 pneumonia and pneumonia) after 2 years.

“Epcoritamab is being explored in earlier lines of therapy, including in ongoing trials for first-line and second-line DLBCL,” Karimi concluded.

References

1. 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.J Clin Oncol. 2025;43(suppl_16):7043. doi:10.1200/JCO.2025.43.16_suppl.7043
2. 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 June 5, 2025. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-epcoritamab-bysp-relapsed-or-refractory-diffuse-large-b-cell
3. Vose JM, Cheah CY, Clausen MR, et al. 3-year update from the Epcore NHL-1 trial: epcoritamab leads to deep and durable responses in relapsed or refractory large B-cell lymphoma. Blood. 2024;144(suppl_1):4480. doi:10.1182/blood-2024-198714