3-Year EPCORE NHL-1 Data Published Showing 53% Have Deep, Durable Remission

In a trial that started with patients heavily pretreated for large B-cell lymphoma (LBCL), more than half who achieved a complete response (CR) with the bispecific epcoritamab (Epkinly; Genmab/AbbVie) remained in remission at 3 years, and 63% were still alive, according to results published early this month.¹

Long-term data from the EPCORE NHL-1 trial were published February 4 in the Annals of Hematology.¹ An earlier presentation of these data took place during the 66th American Society of Hematology Annual Meeting and Exposition in San Diego, California, in December 2024.²

Among patients in the trial who achieved a CR, 53% remained in remission at the time of data cutoff, with the longest CR exceeding 43 months. This occurred despite the fact that 75% of the patients were refractory to at least 2 lines of treatment and 39% had already received chimeric antigen receptor (CAR) T-cell therapy. In addition, of the 19 patients evaluable for measurable residual disease (MRD) assessment, 45% achieved MRD negativity at some point during the study.¹

“An estimated 53% of patients with a CR remained progression free at 3 years, and an esti­mated 75% of patients with a CR had not initiated a new anti-lymphoma therapy at 3 years,” investigators wrote.¹

EPCORE NHL-1 (NCT03625037) is a multicohort, single-arm, phase 1/2 trial conducted at 54 global sites. It evaluated epcoritamab, a subcutaneous CD3xCD20 bispecific antibody, in 157 patients with relapsed or refractory (R/R) CD20+ mature B-cell non-Hodgkin lymphoma; these included 139 patients with diffuse large B-cell lymphoma (DLBCL). After a step-up dosing, treatment moved from every 2 weeks to every 4 weeks, and patients remained on epcoritamab until disease progression or unacceptable toxicity.¹

Data from EPCORE-NHL-1 led to FDA’s accelerated approval of epcoritamab in R/R DLBCL in May 2023³; epcoritamab also received accelerated approval for R/R follicular lymphoma (FL) in June 2024.⁴

More recently, in November 2025, the FDA approved epcoritamab in combination with lenalidomide and rituximab, a combination known as R², to treat FL as early as the first relapse, based on results of the phase 3 EPCORE FL-1 trial (NCT05409066).⁵

According to the study authors, this extended durability suggests the potential for long-term disease-free survival for a subset of patients. “Prolonged CR and survival in complete responders, alongside sustained MRD negativity and a manageable safety profile, support epcoritamab monotherapy as an effective therapy with durable outcomes for patients with challenging-to-treat R/R LBCL,” they wrote.

Other results reported at the 3-mark include:

• Patients enrolled had a median age of 64.0 years; 60% were male, 61% had primary refractory disease, and 29% had progressed within 6 months of prior CAR T-cell therapy.
• The trial’s primary end point was overall response rate (ORR). At the 3-year mark, the ORR was 59%, with a CR rate of 41%; both rates were maintained from prior analyses, “demonstrating the stability of treatment outcomes over time,” the investigators wrote.
• As of May 3, 2024, median follow-up was 37.1 months (range, 0.3 to 45.5). Median duration of response was 20.8 months (95% CI, 13.0-32.0).
• Median duration of CR was 36.1 months (95% CI, 20.2–not reached [NR]), “representing one of the longest median durations of complete response for approved bispecific antibodies in this patient population.”
• Median progression-free survival for the overall study population was 4.2 months (95% CI, 2.8–5.5) with the investigators reporting that “Most patients who remained on epcoritamab beyond 1 year of treatment remained progression free.”
• Among the 47 patients who responded for at least 1 year, 11% had disease progression between 1 year and 2 years of treatment; of the remaining 29 who stayed on treatment beyond 2 years, 7% had disease progression after 2 years.
• The median OS was 18.5 months (95% CI, 11.7–27.7) for the overall population and was NR (95% CI, 36.4–NR) for patients with a CR.

Safety. Long-term safety results were consistent with previous reports. Cytokine release syndrome was the most common adverse event (AE), seen in 51% of patients, with no new cases in the extended follow-up. Cases that occurred took place mostly during cycle 1 after the first full dose and were mostly low-grade (grade 1, 32%; grade 2, 16%). Infections were seen in 57% of patients, with grade 1 and 2 infections accounting for 23% and 34%, respectively.¹

COVID-19 contributed to infection-related AEs of grade 3 or higher, which were seen in 24% of patients; rates were consistent (3% to 17%) across 12-week intervals up to week 144. Treatment-emergent AEs led to discontinuation in 17% of patients, with COVID-19 being the most common reason. Deaths attributable to AEs occurred in 13% of patients.¹

Other results. Epcoritamab is being further investigated as a mono­therapy and in combination with other treatments in several phase 3 trials. In January 2026, topline results for the phase 3 EPCORE DLBCL-1 trial (NCT04628494) were reported by Genmab and AbbVie. EPCORE DLBCL-1 involves patients with R/R DLBCL who were treated with subcutaneous epcoritamab vs investigator’s choice chemoimmunotherapy.⁶

The study showed a 26% improvement in PFS (HR, 0.74; 95% CI, 0.60-0.92), with improvements seen in CR rates, duration of response, and time to next treatment among patients treated with epcoritamab. According to the statement, the trial did not demonstrate a statistically significant improvement in OS (HR, 0.96; 95% CI, 0.77-1.20).

References

1. Karimi YH, Cheah CY, Clausen MR, et al. Efficacy and safety of epcoritamab in relapsed or refractory large B-cell lymphoma: 3-year update from the EPCORE NHL-1 trial. Ann Hematol. 2026;105(3):79. doi:10.1007/s00277-026-06798-4
2. 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
3. Epkinly (epcoritamab-bysp) approved by US FDA as the first and only bispecific antibody to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). News release. PRNewswire. May 19, 2023. Accessed February 12, 2026. https://bit.ly/3BGQt9j
4. FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory follicular lymphoma. FDA. June 26, 2024. Accessed January 24, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-epcoritamab-bysp-relapsed-or-refractory-follicular-lymphoma
5. Falci L, Nijland M, Huang H, et al. Epcoritamab, lenalidomide, and rituximab versus lenalidomide and rituximab for relapsed or refractory follicular lymphoma (EPCORE FL-1): a global, open-label, randomised, phase 3 trial. Lancet. Published online December 7, 2025. doi:10.1016/S0140-6736(25)02360-8
6. Genmab announces topline results for epcoritamab (DuoBody® CD3xCD20) from phase 3 EPCORE® DLBCL-1 trial in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). News release. Genmab. January 16, 2026. Accessed February 12, 2026. https://ir.genmab.com/news-releases/news-release-details/genmab-announces-topline-results-epcoritamab-duobodyr-cd3xcd20